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Last Updated :2024/08/21

Researcher Profile and Settings

Master

Affiliation (Master)

  • Faculty of Medicine　Internal Medicine　Internal Medicine

Affiliation (Master)

  • Faculty of Medicine　Internal Medicine　Internal Medicine

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Profile and Settings

Affiliation

  • University of Glasgow, School of Cardiovascular & Metabolic Health, Honorary Clinical Senior Lecturer

Degree

  • MD（2003/03 National Defense Medical College）
  • PhD（2012/03 Keio University）

Profile and Settings

  • Profile

    -Imperial College London
    Home - Dr Toshiyuki Nagai - Imperial College London
    https://www.imperial.ac.uk/people/t.nagai

    -University of Glasgow
    https://www.gla.ac.uk/researchinstitutes/healthwellbeing/research/robertsoncentreforbiostatistics/staff/?webapp=staffcontact&action=person&id=4edfebe08493

  • Name (Japanese)

    Nagai

  • Name (Kana)

    Toshiyuki

  • Name

    201801008987736924

Alternate Names

Affiliation

  • University of Glasgow, School of Cardiovascular & Metabolic Health, Honorary Clinical Senior Lecturer

Achievement

Research Interests

  • Cardiovascular Medicine   Clinical Heart Failure   心筋炎・心筋症   人工知能   個別化医療   Immune response, Inflammation   Cardiac Sarcoidosis   

Research Areas

  • Life sciences / Cardiology

Research Experience

  • 2024/02 - Today 英国グラスゴー大学, 心血管代謝学部, 客員臨床上級講師
  • 2020/04 - Today Hokkaido University Faculty of Medicine and Graduate School of Medicine Associate Professor
  • 2019/03 - 2024/03 University of Glasgow Robertson Centre for Biostatistics Honorary Senior Lecturer
  • 2018/12 - 2021/12 Imperial College London National Heart and Lung Institute Honorary Senior Lecturer
  • 2018/11 - 2020/03 Hokkaido University Faculty of Medicine and Graduate School of Medicine Senior Lecturer
  • 2016/12 - 2018/12 Imperial College London National Heart and Lung Institute Sponsored Researcher
  • 2018/01 - 2018/10 Hokkaido University Hokkaido University Hospital
  • 2012/07 - 2016/12 国立循環器病研究センター 心臓血管内科部門 医師（医員）
  • 2011/04 - 2012/06 国立病院機構 埼玉病院 循環器内科 医師（医員）
  • 2008/04 - 2009/03 慶應義塾大学医学部 循環器内科学 助教
  • 2006/11 - 2008/03 平塚市民病院 内科・循環器科 医員
  • 2005/08 - 2006/10 自衛隊横須賀病院 医員
  • 2003/06 - 2005/07 防衛医科大学校病院 研修医

Education

  • 2009/04 - 2012/03  Keio University  Graduate School of Medicine  Ph.D.
  • 1997/04 - 2003/03  Naional Defense Medical College  School of Medicine  M.D.

Committee Memberships

  • 2024/02 - Today   WASOG/AASOG   WASOG/AASOG 2025 Planning Committee Member
  • 2022/03 - Today   Fellow of Japanese Circulation Society（FJCS）
  • 2020/12 - Today   Fellow of European Society of Cardiology（FESC）
  • 2020/08 -2024/07   Japanese Circulation Society   Editorial Board in Circulation Journal (Executive editor)

Awards

  • 2024/03 日本循環器学会 2023年度Circulation Journal Best Reviewer Award
     
    受賞者: 永井 利幸
  • 2023/03 日本循環器学会 2022年度Circulation Journal Best Reviewer Award
     
    受賞者: 永井利幸
  • 2022/03 日本循環器学会 2021年度Circulation Journal Best Reviewer Award
     
    受賞者: 永井利幸
  • 2021/03 日本循環器学会 2020年度Circulation Journal Best Reviewer Award
     
    受賞者: 永井利幸
  • 2021/02 北海道科学技術奨励賞（知事表彰）
     
    受賞者: 永井利幸
  • 2020/11 日本医師会 医学研究奨励賞
     
    受賞者: 永井利幸
  • 2020/10 日本サルコイドーシス／肉芽腫性疾患学会 学術賞 千葉保之・本間日臣記念賞
     
    受賞者: 永井利幸
  • 2020/01 日本心臓財団 2019年度 雑誌 「心臓」 年間優秀査読賞
     
    受賞者: 永井利幸
  • 2019/03 北海道大学大学院医学研究院 第38回高桑榮松奨学基金奨励賞
     
    受賞者: 永井利幸
  • 2018/01 日本心臓財団 2017年度 雑誌 「心臓」 年間優秀査読賞
     
    受賞者: 永井利幸
  • 2016/10 第20 回日本心不全学会学術集会 Young Investigator’s Award 優秀賞
     
    受賞者: 永井利幸
  • 2016/03 第80 回日本循環器学会学術集会 第33 回Young Investigator’s Award 優秀賞
     
    受賞者: 永井利幸
  • 2015/11 第35 回日本サルコイドーシス/肉芽腫性疾患学会総会 Young Investigator’s Award 最優秀賞
     
    受賞者: 永井利幸
  • 2014/11 第34 回日本サルコイドーシス/肉芽腫性疾患学会総会 Young Investigator’s Award 最優秀賞
     
    受賞者: 永井利幸
  • 2014/11 第36 回心筋生検研究会 Young Investigator’s Award 優秀賞
     
    受賞者: 永井利幸
  • 2011/10 第31 回日本サルコイドーシス/肉芽腫性疾患学会総会 Young Investigator’s Award 最優秀賞
     
    受賞者: 永井利幸
  • 2011/07 第15 回炎症と循環器疾患研究会 最優秀演題賞
     
    受賞者: 永井利幸
  • 2010/07 第31 回心筋梗塞研究会 優秀演題賞
     
    受賞者: 永井利幸

Published Papers

  • Taro Koya, Toshiyuki Nagai, Atsushi Tada, Motoki Nakao, Suguru Ishizaka, Yoshifumi Mizuguchi, Hiroyuki Aoyagi, Fusako George, Shogo Imagawa, Yusuke Tokuda, Yoshiya Kato, Masashige Takahashi, Hiroto Sakai, Masaharu Machida, Kenichi Matsutani, Takahiko Saito, Hiroshi Okamoto, Toshihisa Anzai
    International journal of cardiology 132452 - 132452 2024/08/14 
    BACKGROUND: Although clinical guidelines recommend self-care assessment for patients with chronic heart failure (CHF), its prognostic significance remains controversial. This study aimed to compare the prognostic significance of self-care behavior on mortality between patients with and without a history of recent hospitalization for heart failure (HF). METHODS: We analyzed consecutive 1907 CHF patients from a Japanese multicenter registry (January 2020-June 2023) using the 9-item European Heart Failure Self-care Behavior Scale (EHFScBS-9) at enrolment. Suboptimal self-care behavior was defined as a score < 70 on the EHFScBS-9. Patients were divided into recent (within 30 days post-discharge, n = 664) and no recent hospitalization for HF groups (n = 1263), respectively. The primary outcome was a composite of all-cause death and rehospitalization for HF. RESULTS: During a median follow-up period of 427 (interquartile range 273-630) days, the primary outcome occurred in 100 patients. Patients with suboptimal self-care behavior exhibited a higher incidence of the primary outcome in the recent hospitalization for HF group (p = 0.020) but not in the no recent hospitalization for HF group (P = 0.16). Multivariable regressions showed suboptimal self-care behavior was independently associated with the primary outcome in the recent hospitalization for HF group with a significant interaction (P = 0.029). CONCLUSION: In patients recently hospitalized for HF, but not in those without a recent hospitalization history for HF, suboptimal self-care behavior was associated with adverse events. This indicates the importance of self-care education for these patients.
  • Tatsuhiro Shibata, Atsushi Mizuno, Takashi Ohmori, Shogo Oishi, Kimitaka Nishizaki, Takeru Nabeta, Takuya Kishi, Toshiyuki Nagai, Toshihisa Anzai
    Journal of cardiology 2024/06/03 
    BACKGROUND: Palliative care (PC) benefits cancer patients and those with heart failure (HF), improving quality of life and symptom burden. Despite guidelines recommending the integration of PC into HF care, its use remains inadequate, partly due to insufficient public awareness. This study aimed to assess the public awareness of PC for HF in Japan and identify factors associated with awareness. METHODS: A cross-sectional online survey was conducted from March 6-13, 2023, using a panel operated by Intage Inc. (Tokyo, Japan), which has a pool of 3.78 million potential Japanese respondents. The survey included 51,790 participants, matched for sex, age, and region of residence. Participants were asked about their awareness of PC eligibility for HF, along with demographic information, history of hospitalization for sudden illness, outpatient visits, and health status in the previous 2 years. The χ2 test and Cramer's V were used to analyze associations between awareness and variables, and multivariate logistic regression was used to estimate awareness predictors. RESULTS: In total, 91 % of participants were unaware of PC eligibility for HF. Age group, healthcare professional occupation, and history of hospitalization for acute myocardial infarction, acute HF, acute pulmonary embolism, and ruptured aortic aneurysm had weak to moderate associations with awareness. Multivariate analysis revealed that a history of hospitalization for sudden cardiovascular illness and being a healthcare professional were positively related to awareness, while age, female sex, and being married were associated with lower odds of awareness. CONCLUSION: The low public awareness of PC for HF in Japan underscores the importance of increasing awareness of the eligibility of PC for HF, as well as cancer, to integrate PC into HF practice as basic care.
  • Michito Murayama, Sanae Kaga, Airi Onoda, Hisao Nishino, Shinobu Yokoyama, Mana Goto, Yukino Suzuki, Yusuke Yanagi, Yui Shimono, Kosuke Nakamura, Hiroyuki Aoyagi, Yoji Tamaki, Suguru Ishizaka, Hiroyuki Iwano, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    Ultrasound in medicine & biology 2024/06/03 
    OBJECTIVE: Blood flow in the hepatic veins and superior vena cava (SVC) reflects right heart filling; however, their Doppler profiles are often not identical, and no studies have compared their diagnostic efficacies. We aimed to determine which venous Doppler profile is reliable for detecting elevated right atrial pressure (RAP). METHODS: In 193 patients with cardiovascular diseases who underwent cardiac catheterization within 2 d of echocardiography, the hepatic vein systolic filling fraction (HV-SFF) and the ratio of the peak systolic to diastolic forward velocities of the SVC (SVC-S/D) were measured. HV-SFF < 55% and SVC-S/D < 1.9 were regarded as elevated RAP. We also calculated the fibrosis 4 index (FIB-4) as a serum liver fibrosis marker. RESULTS: HV-SFF and SVC-S/D were feasible in 177 (92%) and 173 (90%) patients, respectively. In the 161 patients in whom both venous Doppler waveforms could be measured, HV-SFF and SVC-S/D were inversely correlated with RAP (r = -0.350, p < 0.001; r = -0.430, p < 0.001, respectively). SVC-S/D > 1.9 showed a significantly higher diagnostic accuracy of RAP elevation compared with HV-SFF < 55% (area under the curve, 0.842 vs. 0.614, p < 0.001). Multivariate analyses showed that both FIB-4 (β = -0.211, p = 0.013) and mean RAP (β = -0.319, p < 0.001) were independent determinants of HV-SFF. In contrast, not FIB-4 but mean RAP (β = -0.471, p < 0.001) was an independent determinant of SVC-S/D. The diagnostic accuracy remained unchanged when HV-SFF < 55% was considered in conjunction with the estimated RAP based on the inferior vena cava morphology. Conversely, SVC-S/D showed an incremental diagnostic value over the estimated RAP. CONCLUSIONS: SVC-S/D enabled a more accurate diagnosis of RAP elevation than HV-SFF.
  • Daishiro Tatsuta, Takuma Sato, Toshiyuki Nagai, Jiro Koya, Kotaro Nishino, Seiichiro Naito, Yoshifumi Mizuguchi, Taro Temma, Kiwamu Kamiya, Hisashi Narita, Kenkichi Tsuruga, Toshihisa Anzai
    ESC Heart Failure 2055-5822 2024/05/29 
    Abstract Aims Although patients with heart failure (HF) frequently experience considerable symptom burden and require significant care, most HF patients do not receive timely intervention due to the absence of a standardized method for identifying those in need of palliative care. The Needs Assessment Tool: Progressive Disease‐Heart Failure (NAT: PD‐HF) assesses the palliative care needs of patients with HF. However, its validity and reliability have yet to be fully examined. We aimed to assess the validity and reliability of the NAT: PD‐HF in Japanese patients with HF. Methods We prospectively enrolled 106 consecutive patients with chronic HF admitted to our university hospital between February 2023 and July 2023. Their caregivers (n = 95) and healthcare providers (n = 17) were also included. The NAT: PD‐HF was translated from English to Japanese using a forward–backward translation procedure and adapted based on Japanese cultural and medical backgrounds by our professional multidisciplinary team. We assessed the internal consistency of the Japanese NAT: PD‐HF version with Cronbach's alpha coefficient and the inter‐rater and test–retest reliabilities with Cohen's kappa coefficient. After using the tool, all participants were asked to complete a questionnaire about the tool to determine its validity. Results The proportion of female patients in this study was 47 (44%). The median age was 72 years [interquartile range (IQR) 59–81]. The median time spent assessing the patients' and their caregivers' needs using the Japanese NAT: PD‐HF was 14 min (IQR 12–17). The Cronbach's alpha coefficient was 0.82, and the minimum kappa coefficient was 0.77 for inter‐rater reliability and 0.88 for test–retest reliability. In total, 103 patients (97%) and all caregivers responded that the tool was easy to understand. One hundred (94%) patients and 89 (94%) caregivers felt that the tool would improve the quality of care, and 102 (96%) patients and 91 (96%) caregivers indicated that the discussions using this tool allowed them to confide in all their burdens and care needs. All healthcare providers expressed that this tool is helpful in understanding the burden and care needs of both patients and caregivers comprehensively. Conclusions The NAT: PD‐HF is a reliable and valid tool for Japanese patients with HF and their caregivers. This tool was very well accepted by patients, caregivers and healthcare providers to identify burdens and care needs.
  • Yuta Kobayashi, Toshiyuki Nagai, Kiwamu Kamiya, Satonori Tsuneta, Yasushige Shingu, Kento Wakabayashi, Kohsuke Kudo, Yoshihiro Matsuno, Satoru Wakasa, Toshihisa Anzai
    Circulation journal : official journal of the Japanese Circulation Society 88 (6) 1008 - 1008 2024/05/24
  • Atsushi Tada, Toshiyuki Nagai, Toshihisa Anzai
    International journal of cardiology 132204 - 132204 2024/05/23
  • Hiroyuki Aoyagi, Hiroyuki Iwano, Yoji Tamaki, Michito Murayama, Suguru Ishizaka, Ko Motoi, Kosuke Nakamura, Mana Goto, Yukino Suzuki, Shinobu Yokoyama, Hisao Nishino, Sanae Kaga, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    Echocardiography (Mount Kisco, N.Y.) 41 (4) e15808  2024/04 
    BACKGROUND: The assessment of left ventricular (LV) filling pressure (FP) is important for the management of aortic stenosis (AS) patients. Although, it is often restricted for predict LV FP in AS because of mitral annular calcification and a certain left ventricular hypertrophy. Thus, we tested the predictive ability of the algorithm for elevated LV FP in AS patients and also applied a recently-proposed echocardiographic scoring system of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score. METHODS: We enrolled consecutive 116 patients with at least moderate AS in sinus rhythm who underwent right heart catheterization and echocardiography within 7 days. Mean pulmonary artery wedge pressure (PAWP) was measured as invasive parameter of LV FP. LV diastolic dysfunction (DD) was graded according to the ASE/EACVI guidelines. The VMT score was defined as follows: time sequence of opening of mitral and tricuspid valves was scored to 0-2 (0: tricuspid valve first, 1: simultaneous, 2: mitral valve first). When the inferior vena cava was dilated, one point was added and VMT score was finally calculated as 0-3. RESULTS: Of the 116 patients, 29 patients showed elevated PAWP. Ninety patients (93%) and 67 patients (63%) showed increased values for left atrium volume index (LAVI) and E/e', respectively when the cut-off values recommended by the guidelines were applied and thus the algorism predicted elevated PAWP with a low specificity and positive predictive value (PPV). VMT ≥ 2 predicted elevated PAWP with a sensitivity of 59%, specificity of 90%, PPV of 59%, and negative predictive value of 89%. An alternative algorithm that applied tricuspid regurgitation velocity and VMT scores was tested, and its predictive ability was markedly improved. CONCLUSION: VMT score was applicable for AS patients. Alternative use of VMT score improved diagnostic accuracy of guideline-recommended algorism.
  • Motoki Nakao, Toshiyuki Nagai, Toshihisa Anzai
    International Journal of Cardiology 132014 - 132014 0167-5273 2024/04
  • Yukio Aikawa, Soshiro Ogata, Satoshi Honda, Toshiyuki Nagai, Shunsuke Murata, Isao Morii, Toshihisa Anzai, Kunihiro Nishimura, Teruo Noguchi
    International journal of cardiology 399 131776 - 131776 2024/03/15 
    BACKGROUND: The association between prolonged delirium during hospitalization and long-term prognosis in patients with acute heart failure (AHF) admitted to the cardiac intensive care unit (CICU) has not been fully elucidated. METHODS: We conducted a prospective registry study of patients with AHF admitted to the CICU at 2 hospitals from 2013 to 2021. We divided study patients into 3 groups according to the presence or absence of delirium and prolonged delirium as follows: no delirium, resolved delirium, or prolonged delirium. Main outcomes were in-hospital mortality and 3-year mortality after discharge. RESULTS: A total of 1555 patients with AHF (median age, 80 years) were included in the analysis. Of these, 406 patients (26.1%) developed delirium. We divided patients with delirium into 2 groups: the resolved delirium group (n = 201) or the prolonged delirium group (n = 205). Multivariate Cox proportional hazards models for long-term prognosis demonstrated that the prolonged delirium group had a higher incidence of all-cause death (hazard ratio [HR], 1.52; 95% CI, 1.08 to 2.14) and non-cardiovascular death (HR, 1.84; 95% CI, 1.21 to 2.78) than the resolved delirium group. Regarding in-hospital outcomes, multivariate logistic regression modeling showed that prolonged delirium is associated with all-cause death (odds ratio [OR], 9.55; 95% confidential interval [CI], 2.99 to 30.53) and cardiovascular death (OR, 13.02; 95% CI, 2.86 to 59.27) compared with resolved delirium. CONCLUSIONS: Prolonged delirium is associated with worse long-term and short-term outcomes than resolved delirium in patients with AHF.
  • Sho Kazui, Sakae Takenaka, Toshiyuki Nagai, Satonori Tsuneta, Kenji Hirata, Yoshiya Kato, Hirokazu Komoriyama, Yuta Kobayashi, Akinori Takahashi, Kiwamu Kamiya, Taro Temma, Takuma Sato, Atsushi Tada, Yutaro Yasui, Michikazu Nakai, Takahiro Sato, Ichizo Tsujino, Kohsuke Kudo, Satoshi Konno, Toshihisa Anzai
    JACC. Cardiovascular imaging 2024/03/11
  • Satonori Tsuneta, Kenichiro Suno, Yuichiro Fujieda, Masaya Watanabe, Shiro Watanabe, Kenji Hirata, Toshiyuki Nagai, Kohsuke Kudo
    Canadian Journal of Cardiology 2024/03 [Refereed][Not invited]
  • Kazuhiro Nakao, Teruo Noguchi, Hiroyuki Miura, Yasuhide Asaumi, Yoshiaki Morita, Satoshi Takeuchi, Hideo Matama, Keniciro Sawada, Takahito Doi, Hayato Hosoda, Takahiro Nakashima, Satoshi Honda, Masashi Fujino, Shuichi Yoneda, Shoji Kawakami, Toshiyuki Nagai, Kensaku Nishihira, Tomoaki Kanaya, Fumiyuki Otsuka, Michio Nakanishi, Yu Kataoka, Yoshio Tahara, Yoichi Goto, Kengo Kusano, Haruko Yamamoto, Katsuhiro Omae, Hisao Ogawa, Satoshi Yasuda
    Journal of atherosclerosis and thrombosis 31 (2) 122 - 134 2024/02/01 
    AIM: Omega-3 fatty acids have emerged as a new option for controlling the residual risk for coronary artery disease (CAD) in the statin era. Eicosapentaenoic acid (EPA) is associated with reduced CAD risk in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention trial, whereas the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia trial that used the combination EPA/docosahexaenoic acid (DHA) has failed to derive any clinical benefit. These contradictory results raise important questions about whether investigating the antiatherosclerotic effect of omega-3 fatty acids could help to understand their significance for CAD-risk reduction. METHODS: The Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technic EPA/DHA study is a single-center, triple-arm, randomized, controlled, open-label trial used to investigate the effect of EPA/DHA on high-risk coronary plaques after 12 months of treatment, detected using cardiac magnetic resonance (CMR) in patients with CAD receiving statin therapy. Eligible patients were randomly assigned to no-treatment, 2-g/day, and 4-g/day EPA/DHA groups. The primary endpoint was the change in the plaque-to-myocardium signal intensity ratio (PMR) of coronary high-intensity plaques detected by CMR. Coronary plaque assessment using computed tomography angiography (CTA) was also investigated. RESULTS: Overall, 84 patients (mean age: 68.2 years, male: 85%) who achieved low-density lipoprotein cholesterol levels of ＜100 mg/dL were enrolled. The PMR was reduced in each group over 12 months. There were no significant differences in PMR changes among the three groups in the primary analysis or analysis including total lesions. The changes in CTA parameters, including indexes for detecting high-risk features, also did not differ. CONCLUSION: The EPA/DHA therapy of 2 or 4 g/day did not significantly improve the high-risk features of coronary atherosclerotic plaques evaluated using CMR under statin therapy.
  • Yoshifumi Mizuguchi, Motoki Nakao, Toshiyuki Nagai, Yuki Takahashi, Takahiro Abe, Shigeo Kakinoki, Shogo Imagawa, Kenichi Matsutani, Takahiko Saito, Masashige Takahashi, Yoshiya Kato, Hirokazu Komoriyama, Hikaru Hagiwara, Kenji Hirata, Takahiro Ogawa, Takuto Shimizu, Manabu Otsu, Kunihiro Chiyo, Toshihisa Anzai
    European Heart Journal - Digital Health 2023/12/20 
    Abstract Aims Although frailty assessment is recommended for guiding treatment strategies and outcome prediction in elderly patients with heart failure (HF), most frailty scales are subjective and the scores vary among raters. We sought to develop a machine learning-based automatic rating method/system/model of the clinical frailty scale (CFS) for patients with HF. Methods and Results We prospectively examined 417 elderly (≥75 years) with symptomatic chronic HF patients from seven centers between January 2019 and October 2023. The patients were divided into derivation (n = 194) and validation (n = 223) cohorts. We obtained body-tracking motion data using a deep learning-based pose estimation library, on a smartphone camera. Predicted CFS was calculated from 128 key features, including gait parameters, using the Light Gradient Boosting Machine (LightGBM) model. To evaluate the performance of this model, we calculated Cohen’s weighted kappa (CWK) and intraclass correlation coefficient (ICC) between the predicted and actual CFSs. In the derivation and validation datasets, the LightGBM models showed excellent agreements between the actual and predicted CFSs (CWK 0.866, 95% CI 0.807-0.911; ICC 0.866, 95% CI 0.827-0.898; CWK 0.812, 95% CI 0.752-0.868; ICC 0.813, 95% CI 0.761-0.854, respectively). During a median follow-up period of 391 (IQR 273-617) days, the higher predicted CFS was independently associated with a higher risk of all-cause death (HR 1.60, 95% CI 1.02-2.50) after adjusting for significant prognostic covariates. Conclusion Machine learning-based algorithms of automatically CFS rating are feasible, and the predicted CFS is associated with the risk of all-cause death in elderly patients with HF.
  • 中尾 元基, 永井 利幸
    耳鼻咽喉科・頭頸部外科 株式会社医学書院 95 (13) 1078 - 1082 0914-3491 2023/12/20
  • Kosuke Nakamura, Suguru Ishizaka, Kazunori Omote, Yutaro Yasui, Yoshifumi Mizuguchi, Sakae Takenaka, Yui Shimono, Ko Motoi, Hiroyuki Aoyagi, Yoji Tamaki, Sho Kazui, Yuki Takahashi, Kohei Saiin, Seiichiro Naito, Atsushi Tada, Yuta Kobayashi, Takuma Sato, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    Journal of clinical medicine 12 (23) 2023/12/01 
    AIM: The present study aimed to investigate the impact of mild tricuspid regurgitation (TR) on the exercise capacity or clinical outcomes in patients with chronic heart failure (CHF). METHODS AND RESULTS: The study enrolled 511 patients with CHF who underwent cardiopulmonary exercise testing (CPET) between 2013 and 2018. The primary outcome was a composite of heart failure hospitalization and death. Patients with mild TR (n = 324) or significant TR (moderate or greater; n = 60) displayed worse NHYA class and reduced exercise capacity on CPET than those with non-TR (n = 127), but these were more severely impaired in patients with significant TR. A total of 90 patients experienced events over a median follow-up period of 3.3 (interquartile range 0.8-5.5) years. Patients with significant TR displayed a higher risk of events, while patients with mild TR had a 3.0-fold higher risk of events than patients with non-TR (hazard ratio (HR) 3.01; 95% confidence interval (CI), 1.50-6.07). Multivariate Cox regression analysis showed that, compared with non-TR, mild TR was associated with increased adverse events, even after adjustment for co-variates (HR 2.97; 95% CI, 1.35-6.55). CONCLUSIONS: TR severity was associated with worse symptoms, reduced exercise capacity, and poor clinical outcomes. Even patients with mild TR had worse clinical characteristics than those with non-TR.
  • Yuki Takahashi, Kiwamu Kamiya, Toshiyuki Nagai, Satonori Tsuneta, Noriko Oyama-Manabe, Takeshi Hamaya, Sho Kazui, Yutaro Yasui, Kohei Saiin, Seiichiro Naito, Yoshifumi Mizuguchi, Sakae Takenaka, Atsushi Tada, Suguru Ishizaka, Yuta Kobayashi, Kazunori Omote, Takuma Sato, Yasushige Shingu, Kohsuke Kudo, Satoru Wakasa, Toshihisa Anzai
    Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance 25 (1) 60 - 60 2023/10/26 
    BACKGROUND: The differences in pre- and early post-procedural blood flow dynamics between the two major types of bioprosthetic valves, the balloon-expandable valve (BEV) and self-expandable valve (SEV), in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR), have not been investigated. We aimed to investigate the differences in blood flow dynamics between the BEV and SEV using four-dimensional flow cardiovascular magnetic resonance (4D flow CMR). METHODS: We prospectively examined 98 consecutive patients with severe AS who underwent TAVR between May 2018 and November 2021 (58 BEV and 40 SEV) after excluding those without CMR because of a contraindication, inadequate imaging from the analyses, or patients' refusal. CMR was performed in all participants before (median interval, 22 [interquartile range (IQR) 4-39] days) and after (median interval, 6 [IQR 3-6] days) TAVR. We compared the changes in blood flow patterns, wall shear stress (WSS), and energy loss (EL) in the ascending aorta (AAo) between the BEV and SEV using 4D flow CMR. RESULTS: The absolute reductions in helical flow and flow eccentricity were significantly higher in the SEV group compared in the BEV group after TAVR (BEV: - 0.22 ± 0.86 vs. SEV: - 0.85 ± 0.80, P < 0.001 and BEV: - 0.11 ± 0.79 vs. SEV: - 0.50 ± 0.88, P = 0.037, respectively); there were no significant differences in vortical flow between the groups. The absolute reduction of average WSS was significantly higher in the SEV group compared to the BEV group after TAVR (BEV: - 0.6 [- 2.1 to 0.5] Pa vs. SEV: - 1.8 [- 3.5 to - 0.8] Pa, P = 0.006). The systolic EL in the AAo significantly decreased after TAVR in both the groups, while the absolute reduction was comparable between the groups. CONCLUSIONS: Helical flow, flow eccentricity, and average WSS in the AAo were significantly decreased after SEV implantation compared to BEV implantation, providing functional insights for valve selection in patients with AS undergoing TAVR. Our findings offer valuable insights into blood flow dynamics, aiding in the selection of valves for patients with AS undergoing TAVR. Further larger-scale studies are warranted to confirm the prognostic significance of hemodynamic changes in these patients.
  • 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 日本サルコイドーシス 43 (サプリメント号) 64 - 64 1883-1273 2023/10
  • 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 日本サルコイドーシス 43 (サプリメント号) 65 - 65 1883-1273 2023/10
  • 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 日本サルコイドーシス 43 (サプリメント号) 64 - 64 1883-1273 2023/10
  • 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 日本サルコイドーシス 43 (サプリメント号) 65 - 65 1883-1273 2023/10
  • Yui Shimono, Suguru Ishizaka, Kazunori Omote, Kosuke Nakamura, Yutaro Yasui, Yoshifumi Mizuguchi, Sakae Takenaka, Hiroyuki Aoyagi, Yoji Tamaki, Takuma Sato, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    The American journal of cardiology 206 4 - 11 2023/09/05 
    Less data are available regarding the impact of cardiac power output on exercise capacity or clinical outcome in patients with chronic heart failure (CHF). The study enrolled 280 consecutive patients with CHF referred for cardiopulmonary exercise testing and right-sided heart catheterization between 2013 and 2018. The primary outcome was composite of heart failure hospitalization or death. Cardiac power output was calculated as (mean arterial pressure × CO) ÷ 451. Patients with low cardiac power output (<0.53 W, n = 99) were older and had a higher brain natriuretic peptide level than patients with high cardiac power output (≥0.53W, n = 181). Cardiac power output was correlated with peak oxygen consumption (peak V̇O2), peak workload achievement, and ventilatory efficiency (V̇E/V̇CO2 slope) in cardiopulmonary exercise testing, whereas each of cardiac output or mean arterial pressure was not. There were 48 patients with events over a median follow-up period of 3.5 (interquartile range 1.0 to 6.0) years. Patients with low cardiac power output had about a 2-fold higher risk of events than those with a high cardiac power output (hazard ratio 1.97, 95% confidence interval 1.12 to 3.48). In the multivariable Cox regression, a 0.1-W decrease in cardiac power output was associated with 19% increased adverse events (hazard ratio 0.81, 95% confidence interval 0.67 to 0.99). In conclusion, cardiac power output was associated with reduced exercise capacity and poor clinical outcome, suggesting that cardiac power output is useful for risk stratification in patients with CHF. Further study is required to identify therapies targeting cardiac power output to improve the exercise capacity or clinical outcome in patients with CHF.
  • 【心不全に併存する貧血へのアプローチ】
    中尾 元基, 永井 利幸
    日本医事新報 (株)日本医事新報社 (5188) 18 - 32 0385-9215 2023/09 
    [1]心不全における貧血の意義・貧血状態では複数の代償機構が機能する。・代償機構のうち,交感神経系やレニン-アンジオテンシン-アルドステロン(RAA)系の亢進は,心不全患者においては心不全増悪の原因となる。・貧血は心不全患者において全死亡や心不全入院の独立危険因子である。[2]赤血球の分化とヘモグロビンの生合成・恒常性維持のためのヘモグロビンの生合成には20mg/日の鉄を必要とする。・鉄代謝の把握には血清フェリチン濃度とトランスフェリン飽和度(TSAT)が主に用いられる。[3]心不全における貧血の成因・心不全に合併する貧血の原因としては,血液希釈,内因性エリスロポエチンの産生低下,慢性炎症,RAA系の亢進,栄養障害および消化器疾患による鉄欠乏などが関与している。・鉄欠乏には,全身の鉄が減少している絶対的鉄欠乏と,全身の鉄は正常または増加しているが,貯蔵プールに鉄が貯留しているために標的組織に十分な鉄が供給されない機能的鉄欠乏がある。[4]心不全における鉄欠乏・鉄はミトコンドリアを介した心筋におけるエネルギー産生や骨格筋機能の低下などに関与するため,鉄欠乏は貧血の有無にかかわらず不良な予後と関連する。[5]心不全における貧血および鉄欠乏への介入・すべての心不全患者に,血球数,血清フェリチン濃度,TSATによる貧血および鉄欠乏のスクリーニングを定期的に行うことが推奨されている。・鉄欠乏に対する静注鉄剤の予後改善効果が期待されている。(著者抄録)
  • Sho Kazui, Sakae Takenaka, Toshiyuki Nagai, Yoshiya Kato, Hirokazu Komoriyama, Yuta Kobayashi, Akinori Takahashi, Kiwamu Kamiya, Takuma Sato, Atsushi Tada, Yutaro Yasui, Michikazu Nakai, Takahiro Sato, Ichizo Tsujino, Satoshi Konno, Toshihisa Anzai
    International journal of cardiology 389 131268 - 131268 2023/08/15 
    BACKGROUND: Although high-sensitivity cardiac troponins may be sensitive and easily repeatable markers of disease activity in patients with cardiac sarcoidosis (CS), the association between longitudinal cardiac troponin trajectory and adverse events remains unclear. This study aimed to clarify whether longitudinal cardiac troponin levels were associated with adverse events in patients with CS. METHODS: We examined 63 consecutive CS-initiated prednisolone (PSL) patients with available longitudinal high-sensitivity cardiac troponin T (cTnT) data between December 2013 and March 2023. The area under the cTnT trajectory, which reflected cumulative cTnT release, was calculated to assess the association between longitudinal cTnT levels and adverse events. Patients were divided into two groups according to the median area under the cTnT trajectory per month. The primary outcome was a composite of sustained ventricular tachycardia or fibrillation, worsening heart failure, and sudden cardiac death (SCD). RESULTS: In total, 463 cTnT measurements were collected over a median follow-up period of 30.4 (interquartile range [IQR] 15.6-34.2) months. The primary outcome was observed in 12 (19%) patients. A higher area under the cTnT trajectory was significantly associated with an increased incidence of the primary outcome (P = 0.027), while cTnT levels before and one month after initiation of PSL, and these changes were not related to adverse events (P = 0.179, 0.096, and 0.95, respectively). CONCLUSIONS: Longitudinal cTnT trajectory following PSL initiation was associated with adverse cardiac events in patients with CS, suggesting that longitudinal measurement of cTnT would be useful for the early identification of high-risk patients.
  • Kiwamu Kamiya, Makoto Takei, Toshiyuki Nagai, Toru Miyoshi, Hiroshi Ito, Yoshihiro Fukumoto, Hitoshi Obara, Tatsuyuki Kakuma, Ichiro Sakuma, Hiroyuki Daida, Satoshi Iimuro, Hiroaki Shimokawa, Takeshi Kimura, Ryozo Nagai, Toshihisa Anzai
    Journal of atherosclerosis and thrombosis 2023/08/11 
    AIMS: We aimed to investigate the association between non-lipid residual risk factors and cardiovascular events in patients with stable coronary artery disease (CAD) who achieved low-density lipoprotein cholesterol (LDL-C) ＜100 mg/dL from the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study. METHODS: The REAL-CAD study was a prospective, multicenter, open-label trial. As a sub-study, we examined the prognostic impact of non-lipid residual risk factors, including blood pressure, glucose level, and renal function, in patients who achieved LDL-C ＜100 mg/dL at 6 months after pitavastatin therapy. Each risk factor was classified according to severity. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unstable angina requiring emergency hospitalization. RESULTS: Among 8,743 patients, the mean age was 68±8.2 years, and the mean LDL-C level was 84.4±18 mg/dL. After adjusting for the effects of confounders, an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 showed the highest risk of the primary outcome (hazard ratio [HR] 1.92; 95% confidence interval [CI] 1.45-2.53). The combination of eGFR ≤ 60 and hemoglobin A1c (HbA1c) ≥ 6.0% also showed the highest risk of all-cause death (HR, 2.42; 95% CI, 1.72-3.41). CONCLUSIONS: In patients with stable CAD treated with pitavastatin and who achieved guidelines-directed levels of LDL-C, eGFR and HbA1c were independently associated with adverse events, suggesting that renal function and glycemic control could be residual non-lipid therapeutic targets after statin therapy.
  • Eiji Hiraoka, Kengo Tanabe, Shinichiro Izuta, Tadao Kubota, Shun Kohsaka, Amane Kozuki, Kazuhiro Satomi, Hiroki Shiomi, Toshiro Shinke, Toshiyuki Nagai, Susumu Manabe, Yasuhide Mochizuki, Taku Inohara, Mitsuhiko Ota, Tetsuma Kawaji, Yutaka Kondo, Yumiko Shimada, Yohei Sotomi, Tomofumi Takaya, Atsushi Tada, Tomohiko Taniguchi, Kazuya Nagao, Kenichi Nakazono, Yukiko Nakano, Kazuhiko Nakayama, Yuichiro Matsuo, Takashi Miyamoto, Yoshinao Yazaki, Kazuyuki Yahagi, Takuya Yoshida, Kohei Wakabayashi, Hideki Ishii, Minoru Ono, Akihiro Kishida, Takeshi Kimura, Tetsuro Sakai, Yoshihiro Morino
    Circulation journal : official journal of the Japanese Circulation Society 87 (9) 1253 - 1337 2023/08/10
  • Makoto Amaki, Kensuke Moriwaki, Michikazu Nakai, Tetsuhiro Yamano, Atsushi Okada, Hideaki Kanzaki, Masaki Izumo, Hiroki Usuku, Tetsuari Onishi, Toshiyuki Nagai, Yoshihiro Miyamoto, Tomoyuki Fujita, Hiroya Kawai, Yoshihiro Akashi, Kenichi Tsujita, Satoaki Matoba, Junjiro Kobayashi, Chisato Izumi, Toshihisa Anzai
    Journal of cardiology 2023/08/03 
    BACKGROUND: Transcatheter aortic valve replacement (TAVR) for severe symptomatic aortic stenosis (AS) does not benefit all patients. We performed a prospective multicenter study to investigate the cost-effectiveness of TAVR in a Japanese cohort. METHODS AND RESULTS: We prospectively enrolled 110 symptomatic patients with severe AS who underwent TAVR from five institutions. The quality of life measurement (QOL) was performed for each patient before and at 6 months after TAVR. Patients without an improvement in QOL at 6 months after TAVR were defined as non-responders. Pre-TAVR higher QOL, higher clinical frailty scale predicted the non-responders. Three models, 1) conservative treatment for all patients strategy, 2) TAVR for all patients strategy, and 3) TAVR for a selected patient strategy who is expected to be a responder, were simulated. Lifetime cost-effectiveness was estimated using incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained. In comparison to conservative therapy for all patients, ICER was estimated to be 5,765,800 yen/QALY for TAVR for all patients and 2,342,175 yen/QALY for TAVR for selected patient strategy patients, which is less than the commonly accepted ICER threshold of 5,000,000 yen/QALY. CONCLUSIONS: TAVR for selected patient strategy model is more cost-effective than TAVR for all patient strategy without reducing QOL in the Japanese healthcare system. TAVR for selected patient strategy has potential benefit for optimizing the TAVR treatment in patients with high frailty and may direct our resources toward beneficial interventions.
  • Atsushi Tada, Toshiyuki Nagai, Yoshiya Kato, Noriko Oyama-Manabe, Satonori Tsuneta, Michikazu Nakai, Yutaro Yasui, Sho Kazui, Yuki Takahashi, Kohei Saiin, Seiichiro Naito, Sakae Takenaka, Yoshifumi Mizuguchi, Yuta Kobayashi, Suguru Ishizaka, Kazunori Omote, Takuma Sato, Takao Konishi, Kiwamu Kamiya, Kohsuke Kudo, Toshihisa Anzai
    The American journal of cardiology 200 115 - 123 2023/06/10 
    Several liver fibrotic markers are associated with prognosis in patients with heart failure (HF). However, the optimal markers for outcome prediction remain unclear. This study aimed to simultaneously investigate the prognostic value of liver fibrotic markers and the associations between these markers and clinical parameters in patients with HF without organic liver disease. We prospectively examined 211 consecutive patients with chronic HF between April 2018 and August 2021, excluding those with organic liver disease, using liver magnetic resonance imaging and ultrasound. A total of 7 representative liver fibrotic markers were measured in all patients. The primary outcome of interest was the composite of all-cause death and hospitalization for worsening HF. During a median follow-up period of 747 (interquartile range 465 to 1,042) days, the primary outcome occurred in 45 patients. Patients with higher hyaluronic acid and type III procollagen N-terminal peptide (P-III-P) levels showed a significantly higher incidence of the primary outcome than those without (p <0.001 and p = 0.005, respectively). The multivariable Cox regression analysis revealed that hyaluronic acid and P-III-P levels were independently associated with the risk of adverse events (hazard ratio 1.84, 95% confidence interval 1.18 to 2.87 and hazard ratio 2.89, 95% confidence interval 1.32 to 6.34, respectively) even after adjustment for a mortality prediction model, whereas the other 5 markers were not associated with the primary outcome. In conclusion, among the representative liver fibrotic markers, hyaluronic acid and P-III-P might be the optimal markers for outcome prediction in patients with HF.
  • Atsushi Kyodo, Koshiro Kanaoka, Ayaka Keshi, Maki Nogi, Kazutaka Nogi, Satomi Ishihara, Daisuke Kamon, Yukihiro Hashimoto, Yasuki Nakada, Tomoya Ueda, Ayako Seno, Taku Nishida, Kenji Onoue, Tsuneari Soeda, Rika Kawakami, Makoto Watanabe, Toshiyuki Nagai, Toshihisa Anzai, Yoshihiko Saito
    ESC heart failure 10 (3) 2019 - 2030 2023/06 
    AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome with a poor prognosis. Phenotyping is required to identify subtype-dependent treatment strategies. Phenotypes of Japanese HFpEF patients are not fully elucidated, whose obesity is much less than Western patients. This study aimed to reveal model-based phenomapping using unsupervised machine learning (ML) for HFpEF in Japanese patients. METHODS AND RESULTS: We studied 365 patients with HFpEF (left ventricular ejection fraction >50%) as a derivation cohort from the Nara Registry and Analyses for Heart Failure (NARA-HF), which registered patients with hospitalization by acute decompensated HF. We used unsupervised ML with a variational Bayesian-Gaussian mixture model (VBGMM) with common clinical variables. We also performed hierarchical clustering on the derivation cohort. We adopted 230 patients in the Japanese Heart Failure Syndrome with Preserved Ejection Fraction Registry as the validation cohort for VBGMM. The primary endpoint was defined as all-cause death and HF readmission within 5 years. Supervised ML was performed on the composite cohort of derivation and validation. The optimal number of clusters was three because of the probable distribution of VBGMM and the minimum Bayesian information criterion, and we stratified HFpEF into three phenogroups. Phenogroup 1 (n = 125) was older (mean age 78.9 ± 9.1 years) and predominantly male (57.6%), with the worst kidney function (mean estimated glomerular filtration rate 28.5 ± 9.7 mL/min/1.73 m2 ) and a high incidence of atherosclerotic factor. Phenogroup 2 (n = 200) had older individuals (mean age 78.8 ± 9.7 years), the lowest body mass index (BMI; 22.78 ± 3.94), and the highest incidence of women (57.5%) and atrial fibrillation (56.5%). Phenogroup 3 (n = 40) was the youngest (mean age 63.5 ± 11.2) and predominantly male (63.5 ± 11.2), with the highest BMI (27.46 ± 5.85) and a high incidence of left ventricular hypertrophy. We characterized these three phenogroups as atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups, respectively. At the primary endpoint, Phenogroup 1 demonstrated the worst prognosis (Phenogroups 1-3: 72.0% vs. 58.5% vs. 45%, P = 0.0036). We also successfully classified a derivation cohort into three similar phenogroups using VBGMM. Hierarchical and supervised clustering successfully showed the reproducibility of the three phenogroups. CONCLUSIONS: ML could successfully stratify Japanese HFpEF patients into three phenogroups (atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups).
  • 【遠隔医療システムの到達点と可能性】多様化する現場ニーズの支援ツールとしての効用 大学病院と地域中核病院における重症心疾患を対象とした遠隔診療システム運用の有用性
    中尾 元基, 永井 利幸
    新医療 (株)エムイー振興協会 50 (6) 68 - 71 0910-7991 2023/06 
    重症心疾患の診療において、大学病院等と地域中核病院の間で医用画像共有プログラムを用いた遠隔カンファレンスを行うことにより、高難度医療など専門治療の適応判断を含めた診療計画の策定を迅速に行うことができる。(著者抄録)
  • Yoji Tamaki, Hiroyuki Iwano, Michito Murayama, Suguru Ishizaka, Ko Motoi, Hiroyuki Aoyagi, Kosuke Nakamura, Mana Goto, Yukino Suzuki, Shinobu Yokoyama, Hisao Nishino, Masahiro Nakabachi, Sanae Kaga, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    Journal of cardiology 82 (1) 62 - 68 2023/04/27 
    BACKGROUND: Dyspnea is a common symptom in acute heart failure (AHF) patients. Although an accurate and rapid diagnosis of AHF is essential to improve prognosis, estimation of left ventricular (LV) filling pressure (FP) remains challenging, especially for noncardiologists. We evaluated the usefulness of a recently-proposed parameter of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score, to detect AHF in patients complaining of dyspnea. METHODS: Echocardiography and lung ultrasonography (LUS) were performed in 121 consecutive patients (68 ± 14 years old, 75 males) presenting with dyspnea. The VMT score was determined from the atrioventricular valve opening phase (tricuspid valve first: 0, simultaneous: 1, mitral valve first: 2) and inferior vena cava dilatation (absent: 0, present: 1), and VMT ≥2 was judged as positive. LUS was performed with the 8 zones method and judged as positive if 3 or more B-lines were observed in bilateral regions. The AHF diagnosis was performed by certified cardiologists according to recent guidelines. RESULTS: Of the 121 patients, 33 were diagnosed with AHF. The sensitivity and specificity for diagnosing AHF were 64 % and 84 % for LUS and 94 % and 88 % for VMT score. In logistic regression analysis, VMT score showed a significantly higher c-index than LUS (0.91 vs 0.74, p = 0.002). In multivariable analyses, VMT score was associated with AHF independently of clinically relevant covariates and LUS. In addition, serial assessment of VMT score followed by LUS provided a diagnostic flow chart to diagnose AHF (VMT 3: AHF definitive, VMT 2 and LUS positive: AHF highly suspicious; VMT 2 and LUS negative: further investigation is needed; VMT ≤ 1: AHF rejected). CONCLUSIONS: VMT score showed high diagnostic accuracy in diagnosing AHF. Combined assessment of the VMT score and LUS could become a reliable strategy for diagnosis of AHF by non-cardiologists.
  • Hiroyuki Aoyagi, Shingo Tsujinaga, Yuki Takahashi, Seiichiro Naito, Takuma Sato, Takuya Otsuka, Yoji Tamaki, Ko Motoi, Suguru Ishizaka, Yasuyuki Chiba, Kiwamu Kamiya, Hiroyuki Iwano, Toshiyuki Nagai, Satoru Wakasa, Toshihisa Anzai
    Internal medicine (Tokyo, Japan) 2023/03/31 
    We herein report the first case of constrictive pericarditis (CP) induced by long-term pergolide treatment for Parkinson's disease that was assessed using multimodal imaging in a 72-year-old patient with leg edema and dyspnea. The patient was correctly diagnosed with CP using multimodal imaging and successfully treated with pericardiectomy. The treatment history of Parkinson's disease and pathological findings of the removed pericardium suggested that long-term pergolide was the cause of CP. Properly recognizing pergolide as the cause of CP and accurately diagnosing CP using multimodal imaging may contribute to the early detection and treatment of pergolide-induced CP.
  • Kohei Saiin, Sakae Takenaka, Toshiyuki Nagai, Akinori Takahashi, Yoshifumi Mizuguchi, Takao Konishi, Toshihisa Anzai, Daisuke Hotta, Mitsunori Kamigaki, Seiji Yamazaki, Tsutomu Fujita, Takehiro Yamashita, Kandoh Kawahatsu, Takashi Suzuki, Yoichi Nozaki, Taku Sakurada, Takashi Takenaka, Yasumi Igarashi, Takao Makino
    Scientific reports 13 (1) 5120 - 5120 2023/03/29 
    The global coronavirus disease-2019 (COVID-19) pandemic is associated with reduced rate of percutaneous coronary intervention (PCI). However, there were a few data showing how emergency medical system (EMS) and management strategies for acute coronary syndrome (ACS) changed during the pandemic. We sought to clarify changes on characteristics, treatments, and in-hospital mortality of patients with ACS transported via EMS between pre- and post-pandemic. We examined consecutive 656 patients with ACS admitted to Sapporo City ACS Network Hospitals between June 2018 and November 2021. The patients were divided into pre- and post-pandemic groups. The number of ACS hospitalizations declined significantly during the pandemic (proportional reduction 66%, coefficient -0.34, 95% CI -0.50 to -0.18, p < 0.001). The median time from an EMS call to hospital was significantly longer in post-pandemic group than in pre-pandemic group (32 [26-39] vs. 29 [25-36] min, p = 0.008). There were no significant differences in the proportion of patients with ACS receiving PCI, and in-hospital mortality between the groups. The COVID-19 pandemic had a significant impact on EMS and management in patients with ACS. Although a significant decline was observed in ACS hospitalizations, the proportion of patients with ACS receiving emergency PCI remained during the pandemic.
  • Toshiyuki Nagai, Takayuki Inomata, Takashi Kohno, Takuma Sato, Atsushi Tada, Toru Kubo, Kazufumi Nakamura, Noriko Oyama-Manabe, Yoshihiko Ikeda, Takeo Fujino, Yasuhide Asaumi, Takahiro Okumura, Toshiyuki Yano, Kazuko Tajiri, Hiroyuki Matsuura, Yuichi Baba, Haruki Sunami, Shingo Tsujinaga, Yasutoshi Ota, Keiko Ohta-Ogo, Yusuke Ishikawa, Hideo Matama, Nobutaka Nagano, Kimi Sato, Kazushi Yasuda, Yasushi Sakata, Koichiro Kuwahara, Tohru Minamino, Minoru Ono, Toshihisa Anzai
    Circulation journal : official journal of the Japanese Circulation Society 87 (5) 674 - 754 2023/03/10
  • 大動脈弁狭窄症患者に対する左室充満圧の心エコースコアリングシステムの適用(Application of an Echocardiographic Scoring System of Left Ventricular Filling Pressure for Patients with Aortic Stenosis)
    青柳 裕之, 岩野 弘幸, 後藤 真奈, 鈴木 ゆき乃, 村山 迪史, 横山 しのぶ, 西野 久雄, 中鉢 雅大, 中村 公亮, 玉置 陽生, 本居 昂, 石坂 傑, 加賀 早苗, 神谷 究, 永井 利幸, 安斉 俊久
    日本循環器学会学術集会抄録集 87回 PJ065 - 2 2023/03
  • Sakae Takenaka, Takuma Sato, Toshiyuki Nagai, Kazunori Omote, Yuta Kobayashi, Kiwamu Kamiya, Takao Konishi, Atsushi Tada, Yoshifumi Mizuguchi, Yuki Takahashi, Seiichiro Naito, Kohei Saiin, Suguru Ishizaka, Satoru Wakasa, Toshihisa Anzai
    American journal of physiology. Heart and circulatory physiology 324 (3) H355-H363  2023/03/01 
    Although measuring right ventricular (RV) function during exercise is more informative than assessing it at rest, the relationship between RV reserve function, exercise capacity, and health-related quality of life (HRQoL) in patients with left ventricular assist devices (LVAD) remains unresolved. We aimed to investigate whether RV reserve assessed by the change in RV stroke work index (RVSWI) during exercise is correlated with exercise capacity and HRQoL in patients with LVAD. We prospectively assessed 24 consecutive patients with LVAD who underwent invasive right heart catheterization in the supine position. Exercise capacity and HRQoL were assessed using the 6-min walk distance (6 MWD) and peak oxygen consumption (V̇o2) in cardiopulmonary exercise testing, and the EuroQol visual analog scale (EQ-VAS), respectively. The patients were divided into two groups according to the median ΔRVSWI (change from rest to peak exercise). Patients with lower ΔRVSWI had significantly lower changes in cardiac index and absolute value of RV dP/dt than those with higher ΔRVSWI. The ΔRVSWI was positively correlated with 6 MWD (r = 0.59, P = 0.003) and peak V̇o2 (r = 0.56, P = 0.006). In addition, ΔRVSWI was positively correlated with the EQ-VAS (r = 0.44, P = 0.030). In contrast, there was no significant correlation between RVSWI at rest and 6 MWD (r = -0.34, P = 0.88), peak V̇o2 (r = 0.074, P = 0.74), or EQ-VAS (r = 0.127, P = 0.56). Our findings suggest that the assessment of RV reserve function is useful for risk stratification in patients with LVAD.NEW & NOTEWORTHY The change in right ventricular stroke work index (RVSWI) during exercise, not RVSWI at rest, was associated with exercise capacity and HRQoL. Our findings suggest that the assessment of change in RVSWI during exercise as a surrogate of RV reserve function may aid in risk stratification of patients with LVAD.
  • Yutaro Yasui, Kosuke Nakamura, Kazunori Omote, Suguru Ishizaka, Sakae Takenaka, Yoshifumi Mizuguchi, Yui Shimono, Sho Kazui, Yuki Takahashi, Kohei Saiin, Seiichiro Naito, Atsushi Tada, Yuta Kobayashi, Takuma Sato, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    The American journal of cardiology 193 37 - 43 2023/03/01 
    The prognostic impact of peak workload-to-weight ratio (PWR) during cardiopulmonary exercise testing (CPET) and its determinants in patients with chronic heart failure (CHF) are not well understood. Consecutive 514 patients with CHF referred for CPET at the Hokkaido University Hospital between 2013 and 2018 were identified. The primary outcome was a composite of hospitalization because of worsening heart failure and death. PWR was calculated as peak workload normalized to body weight (W/kg) by CPET. Patients with low PWR (cut-off median 1.38 [W/kg], n = 257) were older and more anemic than those with high PWR (n = 257). In CPET, patients with low PWR displayed reduced peak oxygen consumption and impaired ventilatory efficiency compared with those with high PWR, whereas the peak respiratory exchange ratio was not significantly different between the 2 groups. There were 89 patients with events over a median follow-up period of 3.3 (interquartile range 0.8 to 5.5) years. The incidence of composite events was significantly higher in patients with low PWR than in those with high PWR (log-rank p <0.0001). In the multivariable Cox regression, lower PWR was associated with adverse events (hazard ratio 0.31, 95% confidence interval 0.13 to 0.73, p = 0.008). Low hemoglobin concentration was strongly related to impaired PWR (β coefficient = 0.43, per 1 g/100 ml increased, p <0.0001). In conclusion, PWR was associated with worse clinical outcomes, where blood hemoglobin was strongly related to PWR. Further study is required to identify therapies targeting peak workload achievements in exercise stress tests to improve the outcome in patients with CHF.
  • Hikaru Hagiwara, Masaya Watanabe, Takahide Kadosaka, Takuya Koizumi, Yuta Kobayashi, Taro Koya, Motoki Nakao, Satonori Tsuneta, Yoshiya Kato, Hirokazu Komoriyama, Rui Kamada, Toshiyuki Nagai, Kohsuke Kudo, Toshihisa Anzai
    Heart and vessels 2023/01/13 
    Fragmented QRS (fQRS) on a 12-lead electrocardiogram is a known marker of fatal arrhythmias or cardiac adverse events in ischemic and non-ischemic cardiomyopathy patients. Nonetheless, the association between fQRS and clinical outcomes in patients with cardiac sarcoidosis (CS) remains unclear. Herein, we investigated whether fQRS is associated with long-term clinical outcomes in CS patients. A total of 78 patients who received immunosuppressive therapy (IST) for clinically diagnosed CS were retrospectively examined. Patients were classified into two groups according to the presence (n = 19) or absence (n = 59) of fQRS on electrocardiogram before IST. The primary outcome was the composite event of all-cause death, ventricular tachyarrhythmias (VTs), and hospitalization for heart failure. Results of late gadolinium enhancement on cardiac magnetic resonance imaging were also analyzed. During a median follow-up period of 3.7 years (interquartile range: 1.6-6.2 years), the primary outcome occurred more frequently in patients with fQRS than in those without (47% vs. 13%, log-rank p = 0.002). Multivariable Cox regression analyses showed that fQRS was an independent determinant of the primary outcome. The incidence of VTs, within 12 months of IST initiation, was comparable between the two groups; however, late-onset VTs, defined as those occurring ≥ 12 months after IST initiation, occurred more frequently in the fQRS group (21% vs. 2%, log-rank p = 0.002). The scar zone and scar border zone were greater in patients with fQRS than in those without it. In conclusion, our analysis suggests that fQRS is an independent predictor of adverse events, particularly late-onset VTs, in patients with CS.
  • Kohei Saiin, Takao Konishi, Sho Kazui, Yutaro Yasui, Yuki Takahashi, Seiichiro Naito, Sakae Takenaka, Yoshifumi Mizuguchi, Atsushi Tada, Yuta Kobayashi, Yoshiya Kato, Kazunori Omote, Takuma Sato, Kiwamu Kamiya, Toshiyuki Nagai, Shinya Tanaka, Toshihisa Anzai
    American journal of cardiovascular disease 13 (5) 309 - 319 2160-200X 2023 
    BACKGROUND: The characteristics of high-risk coronary atherosclerosis evaluated using optical coherence tomography (OCT) can have a prognostic role. Inflammatory biomarkers may be related to the severity of coronary artery disease. This study investigated the association of high-risk morphological features of coronary plaques on OCT with circulating levels of inflammatory biomarkers and target lesion revascularization (TLR). MATERIALS AND METHODS: We prospectively analyzed the data of 30 consecutive patients with chronic coronary syndrome who underwent percutaneous coronary intervention (PCI) using OCT. The levels of interleukin-6, tumor necrosis factor-alpha, high-sensitivity C-reactive protein, pentraxin 3, vascular endothelial growth factor, and monocyte chemoattractant protein-1 (MCP-1) were measured in plasma samples. Coronary plaque characteristics were scored quantitatively in the form of coronary plaque risk score (CPRS). The estimated high-risk plaque characteristics for TLR were plaque rupture, plaque erosion, calcified nodule, lipid-rich plaque, thin-cap fibroatheroma, cholesterol crystals, macrophage infiltration, microchannels, calcification angle >90°, and microcalcifications. Each high-risk feature carries 1 point. Patients were defined as having a low CPRS (CPRS ≤3) or a high CPRS (CPRS ≥4). RESULTS: The primary outcome was TLR. TLR occurred in 6 (20%) patients within 15 months of PCI. High CPRS on OCT was directly correlated with TLR (P=0.029). In logistic regression analysis, CPRS was associated with TLR (odds ratio, 10.0; 95% confidence interval, 1.34-74.5). Serum MCP-1 level was significantly correlated with the CPRS (P=0.020). CONCLUSIONS: In patients with chronic coronary syndrome, CPRS may be a surrogate predictor of TLR. Serum MCP-1 may aid in the detection of high-risk coronary atherosclerosis.
  • Closed VSDを合併した右室二腔症の手術症例
    齋藤 翔太, 石坂 傑, 下野 裕依, 甲谷 太郎, 神谷 究, 阿部 慎司, 加藤 伸康, 永井 利幸, 若狭 哲, 安斉 俊久
    日本成人先天性心疾患学会雑誌 (一社)日本成人先天性心疾患学会 12 (1) 200 - 200 2023/01
  • Murayama Michito, Kaga Sanae, Onoda Airi, Okada Kazunori, Nakabachi Masahiro, Yokoyama Shinobu, Nishino Hisao, Aoyagi Hiroyuki, Tamaki Yoji, Motoi Ko, Ishizaka Suguru, Iwano Hiroyuki, Nagai Toshiyuki, Tsujino Ichizo, Anzai Toshihisa
    Japanese Journal of Medical Ultrasound Technology 一般社団法人 日本超音波検査学会 advpub 1881-4506 2023 
    Purpose: Sonographic measurements of the inferior vena cava parameters are common noninvasive methods for estimating right atrial pressure. In intermediate cases in which the inferior vena cava parameters showed indeterminate value, the current guidelines of the American Society of Echocardiography recommended using secondary indices, which include restrictive right-sided diastolic filling pattern, the ratio of early-diastolic transtricuspid flow velocity to tricuspid annular velocity, and the hepatic venous systolic filling fraction. We aimed to clarify whether the above secondary indices improve the diagnostic ability of elevated right atrial pressure using inferior vena cava parameters and to test the incremental predictive value of right atrial area measurement. Subjects and Methods: In 128 consecutive patients with various cardiac diseases referred for cardiac catheterization, the elevated right atrial pressure was defined as greater than or equal to 8 mmHg. Based on the inferior vena cava morphology, the estimated right atrial pressure was determined as 3, 8, and 15 mmHg (model 1). Additionally, the restrictive filling pattern, the ratio of early-diastolic transtricuspid flow velocity to tricuspid annular velocity, and the systolic filling fraction were evaluated to reclassify the intermediate value of 8 mmHg (model 2). The right atrial minimum and maximum area and volume were measured at ventricular end diastole and end systole, respectively, and the expansion indices were calculated. Results: Elevated right atrial pressure was observed in 29 patients. Logistic regression analysis showed that estimated right atrial pressure based on the inferior vena cava indices and systolic filling fraction were significantly associated with elevated right atrial pressure (p＜0.05). Restrictive filling pattern was not observed in any of the patients, and the ratio of early-diastolic transtricuspid flow velocity to tricuspid annular velocity was not associated with elevated right atrial pressure. Right atrial morphological and functional parameters were significantly associated with elevated right atrial pressure (p＜0.05). Notably, the minimum right atrial area demonstrated the strongest association with right atrial pressure elevation (odds ratio adjusted for right ventricular systolic function: 10.64, p＜0.01). The predictive ability of model 2 was comparable to that of model 1 (global χ2 value＝9 for model 1, 11 for model 2; p＝0.28). In contrast, incorporated with systolic filling fraction and minimal right atrial area as secondary indices, the predictive ability of the new model was improved compared to that of model 1 (global χ2 value＝9 for model 1, 25 for the new model; p＜0.01). Conclusion: Reclassification using guideline-recommended secondary indices failed to improve the predictive ability of elevated right atrial pressure. In contrast, a combination of systolic filling fraction and minimal right atrial area with inferior vena cava indices improved the predictive ability of elevated right atrial pressure.
  • Atsushi Tada, Toshiyuki Nagai, Taro Koya, Motoki Nakao, Suguru Ishizaka, Yoshifumi Mizuguchi, Hiroyuki Aoyagi, Shogo Imagawa, Yusuke Tokuda, Masashige Takahashi, Yoshiya Kato, Masaharu Machida, Kenichi Matsutani, Takahiko Saito, Toshihisa Anzai
    ESC heart failure 2022/12/10 
    AIMS: Iron deficiency (ID) is a common co-morbidity in patients with heart failure (HF). A recent study showed that ID defined by the current guideline criteria was not associated with worse clinical outcomes, and new ID criteria was proposed in patients with HF. However, the external applicability of the new proposed criteria is unclear. We sought to investigate the applicability of the proposed ID criteria in Japanese patients with HF. METHODS AND RESULTS: We prospectively examined 763 patients with chronic HF from a Japanese multicentre registry. The proposed ID criteria were transferrin saturation (TSAT) < 20% and serum iron ≤13 mmol/L and the guideline ID criteria were serum ferritin <100 ng/mL or, when ferritin was 100-299 ng/mL, TSAT <20%. Among all patients (456 male, mean age 71 ± 13 years), 213 (28%) and 444 (58%) met the proposed and guideline ID criteria, respectively. During a median follow-up period of 436 days (interquartile range 297-565), the primary outcome of all-cause mortality occurred in 56 (7%) patients. There was no significant difference in the primary outcome between the patients with and without guideline ID criteria (P = 0.32), whereas patients with serum iron ≤10 μmol/L showed higher mortality (P = 0.002). In multivariable Cox regressions, the proposed ID criteria, but not guideline ID criteria, were independently associated with the risk of all-cause mortality (HR 2.01, 95% CI 1.16-3.51 and HR 1.32, 95% CI 0.76-2.28, respectively), even after adjustment for covariates. CONCLUSIONS: When defined by the proposed criteria and not the guideline criteria, ID was associated with higher mortality in patients with chronic HF, suggesting that the proposed ID criteria is applicable to the Japanese population.
  • Yasuyuki Chiba, Hiroyuki Iwano, Hiroyuki Aoyagi, Yoji Tamaki, Ko Motoi, Suguru Ishizaka, Michito Murayama, Shinobu Yokoyama, Masahiro Nakabachi, Hisao Nishino, Sanae Kaga, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    Journal of cardiology 81 (4) 404 - 412 2022/12/08 
    BACKGROUND: Although left ventricular (LV) cardiac power output (CPO) is a powerful prognostic indicator in heart failure (HF), the significance of right ventricular (RV) CPO is unknown. In contrast, RV pulsatile load is a key prognostic marker in HF. We investigated the impact of RV-CPO and pulsatile load on cardiac outcome and the prognostic performance of the combined systemic and pulmonary circulation parameters in HF. METHODS: Right heart catheterization and echocardiography were performed in 231 HF patients (62 ± 16 years, LV ejection fraction 42 ± 18 %). Invasive and noninvasive CPOs were calculated from mean systemic or pulmonary arterial pressure and cardiac output. LV-CPO was then normalized to LV mass (LV-P/M). Pulmonary arterial capacitance and the ratio of acceleration time to ejection time (AcT/ET) of RV outflow were used as parameters of RV pulsatile load. The primary endpoints, defined as a composite of cardiac death, HF hospitalization, ventricular arrythmia, and LVAD implantation after the examination, were recorded. RESULTS: Noninvasive CPOs were moderately correlated with invasive ones (LV: ρ = 0.787, RV: ρ = 0.568, and p < 0.001 for both). During a median follow-up period of 441 days, 57 cardiovascular events occurred. Lower LV-P/M and higher RV pulsatile load were associated with cardiovascular events; however, RV-CPO was not associated with the outcome. Echocardiographic LV-P/M and AcT/ET showed significant incremental prognostic value over the clinical parameters. CONCLUSIONS: RV pulsatile load assessed by AcT/ET may be a predictor of clinical events in HF patients. The combination of echocardiographic LV-P/M and AcT/ET could be a novel noninvasive prognostic indicator in HF patients.
  • Koshiro Kanaoka, Kenji Onoue, Satoshi Terasaki, Tomoya Nakano, Michikazu Nakai, Yoko Sumita, Kinta Hatakeyama, Fumio Terasaki, Rika Kawakami, Yoshitaka Iwanaga, Yoshihiro Miyamoto, Yoshihiko Saito, Satoshi Yuda, Masaya Tanno, Toru Takahashi, Hisashi Yokoshiki, Masahiro Toba, Toshihisa Anzai, Toshiyuki Nagai, Takuma Sato, Takashi Takenaka, Seiji Yamazaki, Yuki Katagiri, Toshiharu Takeuchi, Kazuya Sugitatsu, Shigeo Kakinoki, Tomoaki Matsumoto, Kazushi Urasawa, Michinao Tan, Ichizo Tsujino, Mitsunori Kamigaki, Hirofumi Tomita, Kenji Hanada, Motoi Kushibiki, Akihiro Nakamura, Yoshihiro Morino, Takahito Nasu, Satoshi Yasuda, Hideaki Suzuki, Kaoru Iwabuchi, Kanako Tsuji, Shigeto Namiuchi, Tatsuya Komaru, Masahiro Yagi, Shoko Uematsu, Toshiaki Takahashi, Satoru Takeda, Toru Nakanishi, Masafumi Watanabe, Masahiro Wanezaki, Motoyuki Matsui, Shigeo Sugawara, Yasuchika Takeishi, Masayoshi Oikawa, Nobuo Komatsu, Satoshi Suzuki, Hiroshi Okamoto, Noriyuki Takeyasu, Daiki Akiyama, Yutaka Eki, Tsunekazu Kakuta, Tomoyo Sugiyama, Tomomi Koizumi, Koji Ueno, Kazuomi Kario, Mizuri Taki, Yuri Matsumoto, Takanori Yasu, Osamu Nishioka, Shigeto Naito, Makoto Murata, Shoichi Tange, Katsumi Kaneko, Makoto Muto, Hiroshi Inagaki, Shuichi Hasegawa, Eizo Tachibana, Wataru Atsumi, Masahiro Suzuki, Toshihiro Muramatsu, Yoshihiro Yamada, Isao Taguchi, Yoshiaki Fukuda, Akihiro Matsui, Junji Kanda, Koji Hozawa, Akihiko Matsumura, Wataru Shimizu, Takeshi Yamamoto, Issei Komuro, Masaru Hatano, Takanori Ikeda, Shunsuke Kiuchi, Taishiro Chikamori, Yasuyoshi Takei, Kyoko Soejima, Toshinori Minamishima, Hiroyuki Tanaka, Shigeo Shimizu, Masashi Kasao, Tadayuki Kadohira, Tohru Minamino, Kazunori Shimada, Hiroshi Iwata, Yukihiko Momiyama, Takashi Ashikaga, Toshihiro Nozato, Yasumasa Fujiwara, Kenji Inoue, Tetsuo Sasano, Junji Matsuda, Yasuhiro Ishii, Yuichi Ono, Kengo Tanabe, Yu Horiuchi, Toshiro Shinke, Yusuke Kodama, Masao Moroi, Yoshiyuki Yazaki, Taisuke Mizumura, Hiroshi Ohta, Yoshihiro Akashi, Nozomi Kotoku, Yuji Ikari, Mitsunori Maruyama, Yasuhiro Sato, Koichi Tamura, Masaaki Konishi, Hiroshi Suzuki, Mio Ebato, Kazuki Fukui, Kazuhiko Yumoto, Takamasa Iwasawa, Takeshi Kashimura, Kazuyoshi Takahashi, Yoshinobu Okada, Bunji Kaku, Kazuo Usuda, Michiro Maruyama, Tomoki Kameyama, Toshinori Higashikata, Akihiko Hodatsu, Kazuo Osato, Yoji Nagata, Koji Maeno, Kazuo Satake, Takao Sawanobori, Noboru Watanabe, Koichiro Kuwahara, Hirohiko Motoki, Hiroshi Kitabayashi, Kyuhachi Otagiri, Tsunesuke Kono, Daisuke Yamagishi, Yoshikazu Yazaki, Toshiyuki Noda, Itsuro Morishima, Naoki Watanabe, Shinichiro Tanaka, Tomoya Onodera, Ryuzo Nawada, Akinori Watanabe, Masaki Matsunaga, Satoru Suwa, Hiroshi Sakamoto, Hiroki Sakamoto, Takeshi Aoyama, Norio Kanamori, Masahiro Muto, Yuichiro Maekawa, Hayato Ohtani, Yukio Ozaki, Kenshin Naruse, Kenji Takemoto, Haruo Kamiya, Takeshi Suzuki, Yasushi Tomita, Susumu Suzuki, Ryosuke Kametani, Hidekazu Aoyama, Hiroyuki Osanai, Ken Harada, Kenji Kada, Tomoaki Saeki, Koichi Kobayashi, Yasuhiro Ogawa, Akihiro Terasawa, Masanori Shinoda, Mitsutoshi Oguri, Kiyokazu Shimizu, Akinori Sawamura, Atsushi Sugiura, Kosuke Hattori, Shinji Mokuno, Kazuhisa Kondo, Kaoru Dohi, Keishi Moriwaki, Atsunobu Kasai, Tetsuya Nakakuki, Kazuaki Kaitani, Toshikazu Jinnai, Takashi Yamamoto, Hiroyuki Kurata, Atsuyuki Wada, Masaharu Akao, Yasuhiro Hamatani, Kazuya Ishibashi, Yoshiki Akakabe, Yasuhide Asaumi, Hideo Matama, Yasushi Sakata, Hidetaka Kioka, Hiroshi Takaishi, Yoshitaka Iwanaga, Toru Takase, Mitsuo Matsuda, Fumi Sato, Shinji Hasegawa, Kenichi Ishigami, Minoru Ichikawa, Takashi Takagi, Moriaki Inoko, Masaaki Hoshiga, Shuichi Fujita, Yoshihiro Takeda, Takahiko Kawarabayashi, Hideyuki Takaoka, Kenji Nakajima, Tadashi Yuguchi, Tatsuya Kawasaki, Yukinori Shinoda, Yukihito Sato, Masaharu Ishihara, Yuki Matsumoto, Hiroya Kawai, Tomofumi Takaya, Kouki Matsuo, Toshiaki Mano, Kenichi Hirata, Eriko Hisamatsu, Nobutaka Inoue, Koichi Tamita, Naoki Mukohara, Hisashi Shimoyama, Toru Miyajima, Toshihiro Tamura, Yodo Tamaki, Megumi Suzuki, Ryoji Yokota, Manabu Horii, Kazuo Yamanaka, Hiroyuki Kawata, Yukihiro Hashimoto, Yasuki Nakada, Hitoshi Nakagawa, Tomoya Ueda, Taku Nishida, Ayako Seno, Makoto Watanabe, Takashi Akasaka, Takashi Tanimoto, Mamoru Toyofuku, Kazuhiro Yamamoto, Yoshiharu Kinugasa, Masayuki Hirai, Hiroshi Nasu, Kinya Shirota, Tsuyoshi Oda, Takefumi Oka, Kazushige Kadota, Masanobu Ohya, Hiroshi Ito, Kazufumi Nakamura, Soichiro Ogura, Soichiro Fuke, Shiro Uemura, Hiromi Matsubara, Atsuyuki Watanabe, Nobuyuki Morishima, Yasuki Kihara, Takayuki Hidaka, Hironori Ueda, Yujiro Ono, Yuji Muraoka, Miyo Hatanari, Yoshinori Miyamoto, Keigo Dote, Masaya Kato, Masafumi Yano, Mamoru Mochizuki, Yasuhiro Ikeda, Hiroyuki Fujinaga, Shinobu Hosokawa, Masataka Sata, Koji Yamaguchi, Naoko Aki, Tetsuo Minamino, Yuichi Miyake, Yuichiro Takagi, Masayuki Doi, Yoshio Taketani, Hideki Okayama, Tatsuya Shigematsu, Akinori Higaki, Osamu Yamaguchi, Shinji Inaba, Shuntaro Ikeda, Kazuya Kawai, Hiroaki Kitaoka, Toru Kubo, Kenji Ando, Kaoru Inui, Yoshihiro Fukumoto, Kensuke Hori, Takehiro Homma, Tomohiro Kawasaki, Masahiro Mohri, Masaki Fujiwara, Hiroyuki Tsutsui, Tomomi Ide, Shin-Ichiro Miura, Takashi Kuwano, Hideki Shimomura, Toshiaki Kadokami, Masanao Taba, Katsuhiro Kondou, Toru Kubota, Daisuke Nagatomo, Yasushi Mukai, Ryuichi Matsukawa, Hideki Tashiro, Mitsuhiro Shimomura, Koji Maemura, Hiroaki Kawano, Koji Oku, Toshihiko Yamasa, Yoshihisa Kizaki, Tomohiro Sakamoto, Yudai Tamura, Teruhiko Ito, Kazuteru Fujimoto, Kenichi Tsujita, Seiji Takashio, Hirofumi Kurokawa, Naohiko Takahashi, Shotaro Saito, Masaya Arikawa, Yoshisato Shibata, Kensaku Nishihira, Toshihiro Tsuruda, Masahiro Sonoda, Nobuhiko Atsuchi, Mitsuru Ohishi, Koji Higuchi, Masaaki Miyata, Naoya Oketani, Yoshinori Akimoto, Tomohiro Asahi, Minoru Wake
    Circulation 146 (19) 1425 - 1433 0009-7322 2022/11/08 [Refereed]
     
    Background: Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence. Methods: This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis. Results: This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion (<40%) on admission, and ventricular tachycardia or fibrillation on admission day were associated with worse 90-day survival. Severe histologic damage (damaged cardiomyocytes comprising ≥50% of the total cardiomyocytes) was associated with a worse 90-day prognosis in patients with lymphocytic myocarditis. Conclusions: The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP. Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.
  • Atsushi Tada, Toshiyuki Nagai, Yoshiya Kato, Kazunori Omote, Noriko Oyama-Manabe, Satonori Tsuneta, Yusuke Kudo, Mutsumi Nishida, Michikazu Nakai, Yuki Takahashi, Kohei Saiin, Seiichiro Naito, Yuta Kobayashi, Sakae Takenaka, Yoshifumi Mizuguchi, Kiwamu Kamiya, Takao Konishi, Takuma Sato, Kohsuke Kudo, Toshihisa Anzai
    European radiology 33 (3) 2062 - 2074 2022/11/03 
    OBJECTIVES: Evaluation of liver stiffness (LS) by magnetic resonance elastography (MRE) is useful for estimating right atrial pressure (RAP) in patients with heart failure (HF). However, its prognostic implications are unclear. We sought to investigate whether LS measured by MRE (LS-MRE) could predict clinical outcomes in patients with HF. METHODS: We prospectively examined 207 consecutive HF patients between April 2018 and May 2021 after excluding those with organic liver disease. All patients underwent 3.0-T MRE. The primary outcome of interest was the composite of all-cause death and hospitalisation for HF. RESULTS: During a median follow-up period of 720 (interquartile range [IQR] 434-1013) days, the primary outcome occurred in 44 patients (21%), including 15 (7%) all-cause deaths and 29 (14%) hospitalisations for HF. The patients were divided into two groups according to median LS-MRE of 2.54 (IQR 2.34-2.82) kPa. Patients with higher LS-MRE showed a higher incidence of the primary outcome compared to those with lower LS-MRE (p < 0.001). Multivariable Cox regression analyses revealed that LS-MRE value was independently associated with the risk of adverse events (hazard ratio 2.49, 95% confidence interval 1.46-4.24). In multivariable linear regression, RAP showed a stronger correlation with LS-MRE (β coefficient = 0.31, p < 0.001) compared to markers related to liver fibrosis. CONCLUSIONS: In patients without chronic liver disease and presenting with HF, elevated LS-MRE was independently associated with worse clinical outcomes. Elevated LS-MRE may be useful for risk stratification in patients with HF and without chronic liver disease. KEY POINTS: • Magnetic resonance elastography (MRE) is an emerging non-invasive imaging technique for evaluating liver stiffness (LS) which can estimate right atrial pressure. • Elevated LS-MRE, which mainly reflects liver congestion, was independently associated with worse clinical outcomes in patients with heart failure. • The assessment of LS-MRE would be useful for stratifying the risk of adverse events in heart failure patients without chronic liver disease.
  • 長井 梓, 永井 利幸, 矢口 裕章, 藤井 信太朗, 上床 尚, 白井 慎一, 岩田 育子, 松島 理明, 堀内 一宏, 浦 茂久, 安斉 俊久, 矢部 一郎
    神経治療学 (一社)日本神経治療学会 39 (6) S263 - S263 0916-8443 2022/10
  • 日本人心臓サルコイドーシス患者におけるAHA/ACC/HRSガイドライン植込型除細動器適応の外的妥当性
    竹中 秀, 小林 雄太, 永井 利幸, 加藤 喜哉, 小森山 弘和, 永野 伸卓, 神谷 究, 小西 崇夫, 佐藤 琢真, 表 和徳, 多田 篤司, 水口 賢史, 草野 研吾, 植田 初江, 安斉 俊久
    日本サルコイドーシス/肉芽腫性疾患学会雑誌 日本サルコイドーシス 42 (サプリメント号) 64 - 64 1883-1273 2022/10
  • Suguru Ishizaka, Hiroyuki Iwano, Shingo Tsujinaga, Michito Murayama, Satonori Tsuneta, Hiroyuki Aoyagi, Yoji Tamaki, Ko Motoi, Yasuyuki Chiba, Asuka Tanemura, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Kazunori Okada, Brett A Meyers, Pavlos P Vlachos, Takuma Sato, Kiwamu Kamiya, Masaya Watanabe, Sanae Kaga, Toshiyuki Nagai, Noriko Oyama-Manabe, Toshihisa Anzai
    Journal of cardiology 81 (1) 33 - 41 2022/09/16 
    BACKGROUND: Determinants of exercise intolerance in a phenotype of heart failure with preserved ejection fraction (HFpEF) with normal left ventricular (LV) structure have not been fully elucidated. METHODS: Cardiopulmonary exercise testing and exercise-stress echocardiography were performed in 44 HFpEF patients without LV hypertrophy. Exercise capacity was determined by peak oxygen consumption (peak VO2). Doppler-derived cardiac output (CO), transmitral E velocity, systolic (LV-s') and early diastolic mitral annular velocities (e'), systolic pulmonary artery (PA) pressure (SPAP), tricuspid annular plane systolic excursion (TAPSE), and peak systolic right ventricular (RV) free wall velocity (RV-s') were measured at rest and exercise. E/e' and TAPSE/SPAP were used as an LV filling pressure parameter and RV-PA coupling, respectively. RESULTS: During exercise, CO, LV-s', RV-s', e', and SPAP were significantly increased (p < 0.05 for all), whereas E/e' remained unchanged and TAPSE/SPAP was significantly reduced (p < 0.001). SPAP was higher and TAPSE/SPAP was lower at peak exercise in patients showing lower-half peak VO2. In univariable analyses, LV-s' (R = 0.35, p = 0.022), SPAP (R = -0.40, p = 0.008), RV-s' (R = 0.47, p = 0.002), and TAPSE/SPAP (R = 0.42, p = 0.005) were significantly correlated with peak VO2. In multivariable analyses, not only SPAP, but also TAPSE/SPAP independently determined peak VO2 even after the adjustment for clinically relevant parameters. CONCLUSIONS: In HFpEF patients without LV hypertrophy, altered RV-PA coupling by exercise could be associated with exercise intolerance, which might not be caused by elevated LV filling pressure.
  • 末期心不全患者の難治性不整脈に対するICD治療機能停止(deactivation)の検討を多職種で行った一例
    甲谷 次郎, 佐藤 琢真, 立田 大志郎, 西野 広太郎, 小林 雄太, 成田 尚, 敦賀 健吉, 青陽 千果, 池田 陽子, 小島 尚子, 古山 勇気, 小野田 紘子, 加藤 美香, 永井 利幸, 安斉 俊久
    日本心臓病学会学術集会抄録 (一社)日本心臓病学会 70回 C - 3 2022/09
  • COVID-19で入院加療中に冠攣縮性狭心症を併発した褐色細胞腫の一例
    高橋 昌寛, 佐藤 琢真, 立田 大志郎, 甲谷 次郎, 西野 広太郎, 小林 雄太, 小西 崇夫, 永井 利幸, 安斉 俊久
    日本心臓病学会学術集会抄録 (一社)日本心臓病学会 70回 C - 5 2022/09
  • Azusa Nagai, Toshiyuki Nagai, Hiroaki Yaguchi, Shintaro Fujii, Hisashi Uwatoko, Shinichi Shirai, Kazuhiro Horiuchi, Ikuko Iwata, Masaaki Matsushima, Shigehisa Ura, Toshihisa Anzai, Ichiro Yabe
    Journal of the neurological sciences 442 120391 - 120391 2022/08/28 
    OBJECTIVE: In 2012, a large number of myositis cases with anti-mitochondrial M2 (AMA-M2) antibody, which had well been known as the serological hallmark for primary biliary cholangitis (PBC), were reported in Japan. Recently, some case series from Japan, France, America, China and India have shown that approximately 2.5% to 19.5% of patients with myositis have AMA-M2 antibody. The objective of this study was to clarify the prevalence, clinical features, treatment outcome, and severity determinants of AMA-M2 positive myositis. METHODS: This study was a multicenter observational study. We enrolled patients who were diagnosed with myositis during a ten-year period between 2012 and 2021. RESULTS: Of the total of 185 patients with inflammatory myopathy, 17 patients were positive for AMA-M2 antibody. The typical symptoms were weakness mainly involving paravertebral muscles, weight loss, respiratory failure, and cardiac complications. Thirteen of the 17 patients had cardiac complications. A strong correlation was found between respiratory failure and modified Rankin Scale (mRS) score. A strong correlation was also found between respiratory failure and body weight, indicating that weight loss can be an indicator of potential progression of respiratory failure. Six of the 17 patients were complicated by malignancy. CONCLUSIONS: This study showed significant correlations between % vital capacity (VC), body mass index (BMI), and mRS score in patients with AMA-M2-positive myositis. Immunotherapy often improved CK level and respiratory dysfunction. We therefore propose that %VC and BMI should be monitored as disease indicators in treatment of AMA-M2-positive myositis.
  • Takehiro Abe, Kazunori Okada, Michito Murayama, Sanae Kaga, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Hiroyuki Aoyagi, Yoji Tamaki, Ko Motoi, Yasuyuki Chiba, Suguru Ishizaka, Shingo Tsujinaga, Hiroyuki Iwano, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    The International Journal of Cardiovascular Imaging 2022/07/16
  • MitraClip実施後にたこつぼ症候群を呈した1例
    甲谷 次郎, 神谷 究, 立田 大志郎, 西野 広太郎, 高橋 勇樹, 斎院 康平, 内藤 正一郎, 竹中 秀, 多田 篤司, 水口 賢史, 石坂 傑, 小林 雄太, 佐藤 琢真, 永井 利幸, 安斉 俊久
    日本心血管インターベンション治療学会抄録集 30回 [YIA4 - 2] 2022/07
  • Takuma Sato, Yuta Kobayashi, Toshiyuki Nagai, Takeshi Nakatani, Jon Kobashigawa, Yoshikatsu Saiki, Minoru Ono, Satoru Wakasa, Toshihisa Anzai
    International journal of cardiology 356 66 - 72 2022/06/01 
    BACKGROUND: Under the revised heart allocation system in the United States, bridge to transplant (BTT) patients with left ventricular assist device (LVAD) have a longer waitlist period, as they are now lowly prioritized. However, little is known regarding the long-term trajectory of functional capacity (FC) and health-related quality of life (HR-QOL) among BTT-LVAD patients. METHODS: We retrospectively analyzed 442 consecutive patients with BTT-LVAD between April 2013 and May 2019 from a Japanese nationwide registry. FC (New York Heart Association [NYHA] functional class, peak oxygen uptake [VO2], and 6-min walk test [6MWT]) and HR-QOL (European Quality of Life [EQ-5D index] and Visual Analogue Scale [EQ-VAS]) were assessed at baseline and for up to 60 months after LVAD implantation. RESULTS: During the follow-up period of 30 months (IQR 18-42 months), 100 (22.6%) patients underwent transplantation, 37 (8.3%) died, and 14 (3.1%) underwent explantation for recovery. Mean peak VO2, 6MWT distance, EQ-5D index, and EQ-VAS significantly improved 3 months after LVAD implantation (p = 0.0012, p = 0.0037, p < 0.001, p < 0.001, respectively). Furthermore, these improvements were sustained for up to 60 months following LVAD implantation. Major adverse events including device failure, infection, stroke, and bleeding, which occurred within the first 3 months after LVAD implantation may have not affected FC or HR-QOL for up to 60 months (p = 0.15, p = 0.22, respectively). CONCLUSIONS: BTT patients showed long-term preservation of FC and HR-QOL, suggesting that BTT remains an option despite the long waiting time to HTx.
  • Michito Murayama, Hiroyuki Iwano, Ko Motoi, Suguru Ishizaka, Shingo Tsujinaga, Toshiyuki Nagai, Toshihisa Anzai
    Journal of medical ultrasonics (2001) 49 (3) 489 - 491 2022/05/30
  • 中尾 元基, 永井 利幸
    臨床検査 株式会社医学書院 66 (3) 236 - 242 0485-1420 2022/03/15
  • Varun Sundaram, Toshiyuki Nagai, Chern-En Chiang, Yogesh N V Reddy, Tze-Fan Chao, Rosita Zakeri, Chloe Bloom, Michikazu Nakai, Kunihiro Nishimura, Chung-Lieh Hung, Yoshihiro Miyamoto, Satoshi Yasuda, Amitava Banerjee, Toshihisa Anzai, Daniel I Simon, Sanjay Rajagopalan, John G F Cleland, Jayakumar Sahadevan, Jennifer K Quint
    Journal of cardiac failure 28 (3) 353 - 366 2022/03 
    BACKGROUND: Registries show international variations in the characteristics and outcome of patients with heart failure (HF), but national samples are rarely large, and case selection may be biased owing to enrolment in academic centers. National administrative datasets provide large samples with a low risk of bias. In this study, we compared the characteristics, health care resource use (HRU) and outcomes of patients with primary HF hospitalizations (HFH) using electronic health records (EHR) from 4 high-income countries (United States, UK, Taiwan, Japan) on 3 continents. METHODS AND RESULTS: We used electronic health record to identify unplanned HFH between 2012 and 2014. We identified 231,512, 10,991, 36,900, and 133,982 patients with a primary HFH from the United States, the UK, Taiwan, and Japan, respectively. HFH per 100,000 population was highest in the United States and lowest in Taiwan. Fewer patients in Taiwan and Japan were obese or had chronic kidney disease. The length of hospital stay was shortest in the United States (median 4 days) and longer in the UK, Taiwan, and Japan (medians of 7, 9, and 17 days, respectively). HRU during hospitalization was highest in Japan and lowest in UK. Crude and direct standardized in-hospital mortality was lowest in the United States (direct standardized rates 1.8, 95% confidence interval 1.7%-1.9%) and progressively higher in Taiwan (direct standardized rates 3.9, 95% CI 3.8%-4.1%), the UK (direct standardized rates 6.4, 95% CI 6.1%-6.7%), and Japan (direct standardized rates 6.7, 95% CI 6.6%-6.8%). The 30-day all-cause (25.8%) and HF (7.2%) readmissions were highest in the United States and lowest in Japan (11.9% and 5.1%, respectively). CONCLUSIONS: Marked international variations in patient characteristics, HRU, and clinical outcomes exist; understanding them might inform health care policy and international trial design.
  • Reika Nagata, Tomonari Harada, Kazunori Omote, Hiroyuki Iwano, Kotaro Yoshida, Toshimitsu Kato, Koji Kurosawa, Toshiyuki Nagai, Toshihisa Anzai, Masaru Obokata
    ESC heart failure 9 (2) 1454 - 1462 2022/02/15 
    AIMS: Right-sided filling pressure is elevated in some patients with heart failure (HF) and preserved ejection fraction (HFpEF). We hypothesized that right atrial pressure (RAP) would represent the cumulative burden of abnormalities in the left heart, pulmonary vasculature, and the right heart. METHODS AND RESULTS: Echocardiography was performed in 399 patients with HFpEF. RAP was estimated from inferior vena cava morphology and its respiratory change [estimated right atrial pressure (eRAP)], and patients were divided according to eRAP (3 or ≥8 mmHg). Patients with higher eRAP displayed more severe abnormalities in LV diastolic function as well as right heart structure and function than those with normal eRAP. Cardiac deaths or HF hospitalization occurred in 84 patients over a median follow-up of 19.0 months (interquartile range 6.7-36.9). The presence of higher eRAP was independently associated with an increased risk of the composite outcome (adjusted hazard ratio 2.20 vs. normal eRAP group, 95% confidence interval 1.34-3.62, P = 0.002). Kaplan-Meier curves separating the patients into four groups based on eRAP and E/e' ratio showed that event-free survival varied among the groups, providing an incremental prognostic value of eRAP over E/e' ratio. The classification and regression tree analysis demonstrated that eRAP was the strongest predictor of the outcome followed by right ventricular dimension, E/e' ratio, and estimated right ventricular systolic pressure, stratifying the patients into four risk groups (incident rate 8.8-72.2%). CONCLUSIONS: These data may provide new insights into the prognostic role of RAP in the complex pathophysiology of HFpEF and suggest the utility of eRAP for the risk stratification in patients with HFpEF.
  • Michito Murayama, Sanae Kaga, Kazunori Okada, Hiroyuki Iwano, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Shingo Tsujinaga, Yasuyuki Chiba, Suguru Ishizaka, Ko Motoi, Kiwamu Kamiya, Mutsumi Nishida, Toshiyuki Nagai, Toshihisa Anzai
    Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography 35 (7) 727 - 737 2022/02/09 
    BACKGROUND: Superior vena cava (SVC) flow velocity waveform from the supraclavicular window reflects the right atrial pressure (RAP) status. Recent guidelines have stated that the subcostal window is an alternative view for recording SVC flow, but the validity of this approach remains unclear. This study aimed to determine the usefulness of SVC flow evaluation from the subcostal window for estimating RAP. METHODS: Differences in SVC flow characteristics between opposite approaches were examined in 38 healthy adults. In 115 patients with cardiovascular diseases who underwent cardiac catheterization and echocardiography within 48 h, the ratio of peak systolic to diastolic forward SVC flows was measured (SVC-S/D), and the diagnostic ability of SVC-S/D for elevated RAP was tested. A validation cohort was conducted to confirm the diagnostic ability of SVC-S/D in 48 patients who underwent both cardiac catheterization and echocardiography within 24 h. In 59 patients of derivation and validation cohorts, the relationship between SVC flow and RAP was compared between the opposite windows. RESULTS: Both systolic and diastolic SVC flow velocities were higher in the subcostal than in the supraclavicular approach, and effect of position change on the subcostal SVC-S/D was smaller than that on the supraclavicular SVC-S/D in healthy adults. Measurement of SVC-S/D from the subcostal window was feasible in 98 patients (85%). RAP was inversely correlated with SVC-S/D (r=-0.50, P<.001), and was an independent determinant of SVC-S/D after the adjustment for right ventricular systolic function (β=-0.48, P<.001). A cutoff value of 1.9 for SVC-S/D showed 85% sensitivity and 74% specificity in identifying elevated RAP. Additionally, SVC-S/D showed an incremental diagnostic value combined with inferior vena cava size and collapsibility (P=.006). When the cutoff value, SVC-S/D<1.9, was applied to the validation cohort, it showed an acceptable accuracy of 72%, and an incremental diagnostic value combined with inferior vena cava parameters (P=.033). SVC-S/D from the subcostal window correlated better with RAP than that from the supraclavicular window (P<.001, Meng's test). CONCLUSIONS: Measurement of SVC flow velocity from the subcostal window was feasible, and SVC-S/D from the subcostal window could be an additive parameter for estimating RAP.
  • Tomonari Harada, Miho Yamaguchi, Kazunori Omote, Hiroyuki Iwano, Yoshifumi Mizuguchi, Shiro Amanai, Kuniko Yoshida, Toshimitsu Kato, Koji Kurosawa, Toshiyuki Nagai, Kazuaki Negishi, Toshihisa Anzai, Masaru Obokata
    Circulation. Cardiovascular imaging 15 (2) e013495  2022/02 
    BACKGROUND: Cardiac power output is a measure of cardiac performance, and its prognostic significance has been shown in heart failure (HF) with reduced ejection fraction. Patients with HF with preserved ejection fraction may have altered cardiac performance, but the prognostic relevance of cardiac power output is unknown. This study sought to determine the association between cardiac power output and clinical outcomes in HF with preserved ejection fraction and to compare its prognostic effect to other measures of cardiac performance including ventricular-arterial coupling and mechanical efficiency. METHODS: Cardiac power output normalized to left ventricular mass was assessed by echocardiography in 408 patients with HF with preserved ejection fraction. Load-independent contractility (end-systolic elastance), arterial elastance, its coupling (arterial elastance/end-systolic elastance), left ventricular global longitudinal strain, and mechanical efficiency (stroke work/pressure-volume area) were also estimated noninvasively. The primary end point was a composite of cardiovascular mortality or HF hospitalization. RESULTS: The primary composite outcome occurred in 84 patients during a median follow-up of 19.4 months. There was a dose-dependent association between cardiac power output and the composite outcomes, in which patients with the lowest tertile of cardiac power output had >3-fold risk than those with the highest tertile (hazard ratio, 3.04 [95% CI, 1.66-5.57]; P=0.0003). In a multivariable model, lower cardiac power output was independently associated with adverse outcomes (hazard ratio, 0.70 per 1 SD [95% CI, 0.49-0.97]; P=0.03). In contrast, left ventricular size, end-systolic elastance, arterial elastance, arterial elastance/end-systolic elastance ratio, and left ventricular mechanical efficiency were not associated with outcomes. Cardiac power output provided an incremental prognostic effect over the model based on clinical (age, gender, diastolic blood pressure, and atrial fibrillation) and echocardiographic markers (left atrial size, pulmonary pressures, global longitudinal strain, and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular tissue velocity; P=0.03). CONCLUSIONS: In patients with HF with preserved ejection fraction, cardiac power output was independently and incrementally associated with adverse outcomes whereas other markers of cardiac performance were not.
  • Yoshiharu Kinugasa, Kensuke Nakamura, Hiroko Kamitani, Masayuki Hirai, Kiyotaka Yanagihara, Masahiko Kato, Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Yasuchika Takeishi, Kazuhiro Yamamoto, Toshihisa Anzai
    ESC heart failure 9 (2) 1098 - 1106 2022/01/25 
    AIMS: Increased left ventricular mass index (LVMI) disproportionate to electrocardiographic QRS voltage has been reported to be associated with cardiac fibrosis and amyloid infiltration to myocardium. This study aimed to assess whether the LVMI-to-QRS-voltage ratio predicts clinical outcomes in heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, and prospective registration of Japanese patients hospitalized with HFpEF (EF ≥ 50%). LVMI was assessed by echocardiography using the cube formula. QRS voltage was assessed by Sokolow-Lyon voltage criteria. We divided 290 patients in the registry who met inclusion criteria into five groups according to the quintile values of their LVMI-to-QRS-voltage ratio. In the highest quintile group (≥71.8 g/m2 /mV), approximately 50% of the patients had concentric hypertrophy and 30% had eccentric hypertrophy. These patients had the highest proportion of atrial fibrillation (61.4%) and history of pacemaker implantation (12.1%) among the five groups (P < 0.05). During the mean follow-up of 587 ± 300 days, 31.4% of all patients met the composite endpoint of all-cause death or rehospitalization for HF. Even after adjustment for demographic and baseline variables, the highest quintile group had a significantly higher incidence of the composite endpoints than the lowest quintile group (<30.7 g/m2 /mV) (hazard ratio: 2.205, 95% confidence interval: 1.106-4.395, P < 0.05). CONCLUSIONS: A high LVMI-to-QRS-voltage ratio is independently associated with poor outcomes in patients with HFpEF.
  • Takao Konishi, Yuki Takahashi, Sho Kazui, Yutaro Yasui, Kohei Saiin, Seiichiro Naito, Sakae Takenaka, Yoshifumi Mizuguchi, Atsushi Tada, Yuta Kobayashi, Kazunori Omote, Takuma Sato, Kiwamu Kamiya, Toshiyuki Nagai, Shinya Tanaka, Toshihisa Anzai
    Cardiology journal 29 (4) 718 - 719 2022
  • Hiroyuki Natsui, Takao Konishi, Kohei Saiin, Youji Tamaki, Tomoya Sato, Sakae Takenaka, Atsushi Tada, Yoshifumi Mizuguchi, Yuta Kobayashi, Takuma Sato, Rui Kamada, Kiwamu Kamiya, Toshiyuki Nagai, Shinya Tanaka, Toshihisa Anzai
    Cardiology journal 29 (2) 362 - 363 2022
  • Tomonari Harada, Masaru Obokata, Kazunori Omote, Hiroyuki Iwano, Takahiro Ikoma, Kenya Okada, Kuniko Yoshida, Toshimitsu Kato, Koji Kurosawa, Toshiyuki Nagai, Toshihisa Anzai, Barry A Borlaug, Masahiko Kurabayashi
    The American journal of cardiology 162 129 - 135 2022/01/01 
    Tricuspid regurgitation (TR) is common in patients with heart failure with preserved ejection fraction (HFpEF), but it has not been well characterized. We hypothesized that right atrial (RA) remodeling would be associated with TR in HFpEF, forming a type of atrial functional TR (AFTR). Echocardiography was performed in 328 patients with HFpEF. TR severity was defined using a guidelines-based approach. Ventricular functional TR was defined as the presence of right ventricular (RV) systolic pressure >50 mm Hg or RV dilation, and the remaining patients were classified as having AFTR if they had RA dilation or tricuspid annular enlargement. RA dilation was common (78%) in the significant TR group (more than mild), exceeding the prevalence of RV dilation (32%), and RA dilation was correlated with tricuspid annular diameter and TR vena contracta width (r = 0.67 and r = 0.70, both p <0.0001). Despite the absence of RV dilation and pulmonary hypertension, 38% of patients with significant TR had AFTR. Patients with AFTR and those with ventricular functional TR displayed higher heart failure hospitalization rates than those with nonsignificant TR (adjusted hazard ratios, 2.45 and 4.31; 95% confidence interval 1.12 to 5.35 and 2.44 to 7.62, p = 0.02 and p <0.0001, respectively). In conclusion, TR in HFpEF is related to RA remodeling, and the presence of AFTR was associated with poor clinical outcomes. The current data highlight the importance of RA remodeling in the pathophysiology of TR in HFpEF.
  • Atsushi Tada, Toshiyuki Nagai, Kazunori Omote, Hiroyuki Iwano, Shingo Tsujinaga, Kiwamu Kamiya, Takao Konishi, Takuma Sato, Hirokazu Komoriyama, Yuta Kobayashi, Sakae Takenaka, Yoshifumi Mizuguchi, Tomoya Sato, Kazuhiro Yamamoto, Tsutomu Yoshikawa, Yoshihiko Saito, Toshihisa Anzai
    International journal of cardiology 342 43 - 48 2021/11/01 
    BACKGROUND: Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Although the H2FPEF score and HFA-PEFF algorithm have been proposed for diagnosing HFpEF, previous validation studies were conducted in stable chronic heart failure (HF). Moreover, information on their applicability in the Asian population is limited. We sought to investigate these scores' diagnostic performance for HFpEF in Japanese patients recently hospitalized due to acute decompensated HF. METHODS: We examined patients with HFpEF recently hospitalized with acute decompensated HF from a nationwide HFpEF-specific multicenter registry (HFpEF group) and control patients who underwent echocardiography to investigate the cause of dyspnea in our hospital (Non-HFpEF group). RESULTS: The studied population included 372 patients (194 HFpEF group and 178 Non-HFpEF group; HFpEF prevalence, 52%). A high H2FPEF score (6-9 points) could diagnose HFpEF with a high specificity of 97% and a positive predictive value (PPV) of 94%, and a low H2FPEF score (0-1 point) could rule out HFpEF with a high sensitivity of 97% and a negative predictive value (NPV) of 93%. HFpEF could be diagnosed with a high HFA-PEFF score (5-6 points) (specificity, 84%; PPV, 82%) or ruled out with a low HFA-PEFF score (0-1 point) (sensitivity, 99%; NPV, 89%). The H2FPEF score was significantly superior to the HFA-PEFF score in diagnostic accuracy (area under the curve: 0.89 vs. 0.82, respectively, p = 0.004). CONCLUSIONS: The H2FPEF and the HFA-PEFF scores had acceptable diagnostic accuracy in diagnosing HFpEF in Japanese patients.
  • Michito Murayama, Hiroyuki Iwano, Masaru Obokata, Tomonari Harada, Kazunori Omote, Kazuki Kagami, Shingo Tsujinaga, Yasuyuki Chiba, Suguru Ishizaka, Ko Motoi, Yoji Tamaki, Hiroyuki Aoyagi, Masahiro Nakabachi, Hisao Nishino, Shinobu Yokoyama, Asuka Tanemura, Kazunori Okada, Sanae Kaga, Mutsumi Nishida, Toshiyuki Nagai, Masahiko Kurabayashi, Toshihisa Anzai
    European heart journal. Cardiovascular Imaging 23 (5) 616 - 626 2021/10/25 
    AIMS: Elevated left ventricular filling pressure (LVFP) is a powerful indicator of worsening clinical outcomes in heart failure with preserved ejection fraction (HFpEF); however, detection of elevated LVFP is often challenging. This study aimed to determine the association between the newly proposed echocardiographic LVFP parameter, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score, and clinical outcomes of HFpEF. METHODS AND RESULTS: We retrospectively investigated 310 well-differentiated HFpEF patients in stable conditions. VMT was scored from 0 to 3 using two-dimensional echocardiographic images, and VMT ≥2 was regarded as a sign of elevated LVFP. The primary endpoint was a composite of cardiac death or heart failure hospitalization during the 2 years after the echocardiographic examination. In all patients, Kaplan-Meier curves showed that VMT ≥2 (n = 54) was associated with worse outcomes than the VMT ≤1 group (n = 256) (P < 0.001). Furthermore, VMT ≥2 was associated with worse outcomes when tested in 100 HFpEF patients with atrial fibrillation (AF) (P = 0.026). In the adjusted model, VMT ≥2 was independently associated with the primary outcome (hazard ratio 2.60, 95% confidence interval 1.46-4.61; P = 0.001). Additionally, VMT scoring provided an incremental prognostic value over clinically relevant variables and diastolic function grading (χ2 10.8-16.3, P = 0.035). CONCLUSIONS: In patients with HFpEF, the VMT score was independently and incrementally associated with adverse clinical outcomes. Moreover, it could also predict clinical outcomes in HFpEF patients with AF.
  • Yoji Tamaki, Shingo Tsujinaga, Hiroyuki Iwano, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    Journal of echocardiography 21 (2) 81 - 82 2021/10/06
  • Suguru Ishizaka, Hiroyuki Iwano, Ko Motoi, Yasuyuki Chiba, Shingo Tsujinaga, Asuka Tanemura, Michito Murayama, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Kazunori Okada, Sanae Kaga, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    Journal of cardiology 78 (4) 322 - 327 2021/10 
    BACKGROUND: Although the time difference between peak of left ventricular (LV) and aortic systolic pressures (TLV-Ao), which is considered to in part reflect pulsus tardus, is reported to be associated with clinical outcome in aortic stenosis (AS), its physiological determinants remain to be elucidated. We hypothesized that not only AS severity but also LV systolic dysfunction could be associated with occurrence of pulsus tardus. METHODS: TLV-Ao was measured by simultaneous LV and aortic pressure tracing in 74 AS patients and prolonged TLV-Ao was defined as ≥66 ms according to the previous report. Mean transaortic valvular pressure gradient (mPG) and effective orifice area index (EOAI) were estimated by Doppler echocardiography and severe AS was defined as EOAI ≤0.60 cm2/m2. Global longitudinal strain (GLS) was measured by using speckle-tracking method. RESULTS: Although a weak correlation was observed between EOAI and TLV-Ao, there was substantial population showing discordance between the parameters: severe AS despite normal TLV-Ao (10 of 47 patients) and moderate AS despite prolonged TLV-Ao (9 of 17 patients). In severe AS, mPG was significantly higher in patients showing prolonged TLV-Ao (57±20 vs 36±10 mmHg, p<0.0001) whereas GLS was comparable between the groups (-15.2±3.5% vs -14.8±3.2%). In contrast, in moderate AS, GLS was significantly smaller in patients showing prolonged TLV-Ao (-12.6±4.7% vs -17.4±3.4%, p=0.0271) while mPG was comparable (34±7 mmHg vs 35±8 mmHg). Multivariable analysis revealed that not only mPG but also GLS was an independent determinant of TLV-Ao. CONCLUSIONS: The occurrence of pulsus tardus could be associated with not only AS severity but also LV systolic dysfunction in AS patients.
  • Yuta Kobayashi, Takuma Sato, Toshiyuki Nagai, Kenji Hirata, Satonori Tsuneta, Yoshiya Kato, Hirokazu Komoriyama, Kiwamu Kamiya, Takao Konishi, Kazunori Omote, Hiroshi Ohira, Kohsuke Kudo, Satoshi Konno, Toshihisa Anzai
    ESC heart failure 8 (6) 5282 - 5292 2021/09/12 
    AIMS: Although soluble interleukin 2 receptor (sIL-2R) is a potentially useful biomarker in the diagnosis and evaluation of disease severity in patients with sarcoidosis, its prognostic implication in patients with cardiac sarcoidosis (CS) is unclear. We sought to investigate whether sIL-2R was associated with clinical outcomes and to clarify the relationship between sIL-2R levels and disease activity in patients with CS. METHODS AND RESULTS: We examined 83 consecutive patients with CS in our hospital who had available serum sIL-2R data between May 2003 and February 2020. The primary outcome was a composite of advanced atrioventricular block, ventricular tachycardia or ventricular fibrillation, heart failure hospitalization, and all-cause death. Inflammatory activity in the myocardium and lymph nodes was assessed by 18 F-fluorideoxyglucose positron emission tomography/computed tomography. During a median follow-up period of 2.96 (IQR 2.24-4.27) years, the primary outcome occurred in 24 patients (29%). Higher serum sIL-2R levels (>538 U/mL, the median) were significantly related to increased incidence of primary outcome (P = 0.037). Multivariable Cox regression analysis showed that a higher sIL-2R was independently associated with an increased subsequent risk of adverse events (HR 3.71, 95% CI 1.63-8.44, P = 0.002), even after adjustment for significant covariates. sIL-2R levels were significantly correlated to inflammatory activity in lymph nodes (r = 0.346, P = 0.003) but not the myocardium (r = 0.131, P = 0.27). CONCLUSIONS: Increased sIL-2R is associated with worse long-term clinical outcomes accompanied by increased systemic inflammatory activity in CS patients.
  • 佐藤 琢真, 永井 利幸, 安斉 俊久
    薬事 (株)じほう 63 (12) 2479 - 2436 0016-5980 2021/09 
    ＜Points＞▼心不全では原因疾患に応じた治療戦略を構築することが重要であるが、疾患そのものに対する治療だけでなく、患者の価値観や生活背景を考慮した包括的な支援が必要とされる。▼運動・食事・生活習慣の管理や、適切な薬物治療に関する理解は、重症度や原因疾患にかかわらずすべての心不全患者における治療の基盤となる最重要事項である。▼多職種介入のもとで、心不全患者の生活のなかに潜む心不全増悪要因を把握し、それにあわせた適切かつ患者・家族の価値観や思いに沿った心不全セルフケア支援を進め、再入院の予防に努めることは、心不全診療における重要な柱である。(著者抄録)
  • MitraClipを用いた経皮的僧帽弁接合修復術により強心薬を離脱できた重症心不全の一例
    高橋 昌寛, 辻永 真吾, 高橋 勇樹, 佐藤 琢真, 内藤 正一郎, 青柳 裕之, 小林 雄太, 神谷 究, 岩野 弘幸, 永井 利幸, 安斉 俊久
    日本心臓病学会学術集会抄録 (一社)日本心臓病学会 69回 O - 267 2021/09
  • 慢性心不全における右室cardiac power outputの意義
    千葉 泰之, 岩野 弘幸, 本居 昂, 石坂 傑, 辻永 真吾, 村山 迪史, 横山 しのぶ, 中鉢 雅大, 西野 久雄, 岡田 一範, 加賀 早苗, 神谷 究, 永井 利幸, 安斉 俊久
    日本心臓病学会学術集会抄録 (一社)日本心臓病学会 69回 O - 029 2021/09
  • Yuta Kobayashi, Toshiyuki Nagai, Sakae Takenaka, Yoshiya Kato, Hirokazu Komoriyama, Nobutaka Nagano, Kiwamu Kamiya, Takao Konishi, Takuma Sato, Kazunori Omote, Shingo Tsujinaga, Hiroyuki Iwano, Kengo Kusano, Satoshi Yasuda, Hisao Ogawa, Hatsue Ishibashi-Ueda, Toshihisa Anzai
    The American journal of cardiology 152 125 - 131 2021/08/01 
    Cardiac sarcoidosis (CS) is frequently complicated by fatal ventricular arrhythmias. T-peak to T-end interval to QT interval ratio (TpTe/QT) on electrocardiograms (ECG) was proposed as a marker of ventricular repolarization dispersion. Although this ratio could be associated with the incidence of ventricular arrhythmias in cardiovascular diseases, its prognostic implication in patients with CS is unclear. We sought to investigate whether TpTe/QT was associated with long-term clinical outcomes in patients with CS. Ninety consecutive patients with CS in 2 tertiary hospitals who had ECG data before initiation of immunosuppressive therapy between November 1995 and March 2019 were examined. The primary outcome was a composite of advanced atrioventricular block, ventricular tachycardia or ventricular fibrillation (VT/VF), heart failure hospitalization, and all-cause death. During a median follow-up period of 4.70 (interquartile range 2.06-7.23) years, the primary outcome occurred in 21 patients (23.3%). Survival analyses revealed that the primary outcome (p < 0.001), especially VT/VF or sudden cardiac death (p = 0.002), occurred more frequently in patients with higher TpTe/QT (≥ 0.242, the median) than in those with lower TpTe/QT. Multivariable Cox regression analysis showed that a higher TpTe/QT was independently associated with increased subsequent risk of adverse events (hazard ratio1.11, 95% confidence interval 1.03-1.20, p = 0.008) even after adjustment for the significant covariates. In conclusion, a higher TpTe/QT was associated with worse long-term clinical outcomes, especially fatal ventricular arrhythmic events, in patients with cardiac sarcoidosis, suggesting the importance of assessing TpTe/QT as a surrogate for risk stratification in these patients.
  • Seiichiro Naito, Shingo Tsujinaga, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    European Heart Journal - Case Reports 5 (11) ytab298  2021/07/28
  • Michito Murayama, Hiroyuki Iwano, Hisao Nishino, Shingo Tsujinaga, Masahiro Nakabachi, Shinobu Yokoyama, Miho Aiba, Kazunori Okada, Sanae Kaga, Miwa Sarashina, Yasuyuki Chiba, Suguru Ishizaka, Ko Motoi, Mutsumi Nishida, Hitoshi Shibuya, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography 34 (7) 723 - 734 2021/07 
    BACKGROUND: When left ventricular filling pressure (LVFP) increases, the mitral valve opens early and precedes tricuspid valve opening in early diastole. The authors hypothesized that a visually assessed time sequence of atrioventricular valve opening could become a new marker of elevated LVFP. The aim of this study was to test the diagnostic ability of a novel echocardiographic scoring system, the visually assessed time difference between mitral valve and tricuspid valve opening (VMT) score, in patients with heart failure. METHODS: One hundred nineteen consecutive patients who underwent cardiac catheterization within 24 hours of echocardiographic examination were retrospectively analyzed as a derivation cohort. In addition, a prospective study was conducted to validate the diagnostic ability of the VMT score in 50 patients. Elevated LVFP was defined as mean pulmonary artery wedge pressure (PAWP) ≥ 15 mm Hg. The time sequence of atrioventricular valve opening was visually assessed and scored (0 = tricuspid valve first, 1 = simultaneous, 2 = mitral valve first). When the inferior vena cava was dilated, 1 point was added, and VMT score was ultimately graded as 0 to 3. Cardiac events were recorded for 1 year after echocardiography. RESULTS: In the derivation cohort, PAWP was elevated with higher VMT scores (score 0, 10 ± 5; score 1, 12 ± 4; score 2, 22 ± 8; score 3, 28 ± 4 mm Hg; P < .001, analysis of variance). VMT score ≥ 2 predicted elevated PAWP with accuracy of 86% and showed incremental predictive value over clinical variables and guideline-recommended diastolic function grading. These observations were confirmed in the prospective validation cohort. Importantly, VMT score ≥ 2 discriminated elevated PAWP with accuracy of 82% in 33 patients with monophasic left ventricular inflow in the derivation cohort. Kaplan-Meier analysis demonstrated that patients with VMT scores ≥ 2 were at higher risk for cardiac events than those with VMT scores ≤ 1 (P < .001). CONCLUSIONS: VMT scoring could be a novel additive marker of elevated LVFP and might also be associated with adverse outcomes in patients with heart failure.
  • Eiji Kitamura, Takahiro Iizuka, Noritaka Mamorita, Toshiyuki Nagai, Ryo Usui, Atsuko Yanagida, Masaaki Nakamura, Daisuke Ishima, Juntaro Kaneko, Tsugio Akutsu, Naomi Kanazawa, Kazutoshi Nishiyama
    Journal of the Neurological Sciences 426 117472 - 117472 0022-510X 2021/07
  • Hirokazu Komoriyama, Kiwamu Kamiya, Toshiyuki Nagai, Noriko Oyama-Manabe, Satonori Tsuneta, Yuta Kobayashi, Yoshiya Kato, Miwa Sarashina, Kazunori Omote, Takao Konishi, Takuma Sato, Shingo Tsujinaga, Hiroyuki Iwano, Yasushige Shingu, Satoru Wakasa, Toshihisa Anzai
    Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance 23 (1) 81 - 81 2021/06/28 
    BACKGROUND: Pre- and post-procedural hemodynamic changes which could affect adverse outcomes in aortic stenosis (AS) patients who undergo transcatheter aortic valve replacement (TAVR) have not been well investigated. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) enables accurate analysis of blood flow dynamics such as flow velocity, flow pattern, wall shear stress (WSS), and energy loss (EL). We sought to examine the changes in blood flow dynamics of patients with severe AS who underwent TAVR. METHODS: We examined 32 consecutive severe AS patients who underwent TAVR between May 2018 and June 2019 (17 men, 82 ± 5 years, median left ventricular ejection fraction 61%, 6 self-expanding valve), after excluding those without CMR because of a contraindication or inadequate imaging from the analyses. We analyzed blood flow patterns, WSS and EL in the ascending aorta (AAo), and those changes before and after TAVR using 4D flow CMR. RESULTS: After TAVR, semi-quantified helical flow in the AAo was significantly decreased (1.4 ± 0.6 vs. 1.9 ± 0.8, P = 0.002), whereas vortical flow and eccentricity showed no significant changes. WSS along the ascending aortic circumference was significantly decreased in the left (P = 0.038) and left anterior (P = 0.033) wall at the basal level, right posterior (P = 0.011) and left (P = 0.010) wall at the middle level, and right (P = 0.012), left posterior (P = 0.019) and left anterior (P = 0.028) wall at the upper level. EL in the AAo was significantly decreased (15.6 [10.8-25.1 vs. 25.8 [18.6-36.2]] mW, P = 0.012). Furthermore, a significant negative correlation was observed between EL and effective orifice area index after TAVR (r = - 0.38, P = 0.034). CONCLUSIONS: In severe AS patients undergoing TAVR, 4D flow CMR demonstrates that TAVR improves blood flow dynamics, especially when a larger effective orifice area index is obtained.
  • Takahide Kadosaka, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    Circulation journal : official journal of the Japanese Circulation Society 85 (7) 1100 - 1100 2021/06/25
  • Sakae Takenaka, Yuta Kobayashi, Toshiyuki Nagai, Yoshiya Kato, Hirokazu Komoriyama, Nobutaka Nagano, Kiwamu Kamiya, Takao Konishi, Takuma Sato, Kazunori Omote, Yoshifumi Mizuguchi, Atsushi Tada, Tomoya Sato, Hiroyuki Iwano, Kengo Kusano, Hatsue Ishibashi-Ueda, Toshihisa Anzai
    JACC. Clinical electrophysiology 7 (11) 1410 - 1418 2021/06/22 
    OBJECTIVES: This study aimed to assess, among Japanese patients with cardiac sarcoidosis (CS), the implantable cardioverter-defibrillator (ICD) recommendations from the 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death (SCD). BACKGROUND: Although ICDs are used to prevent SCD from ventricular tachycardia or ventricular fibrillation (VT/VF) in patients with CS, the generalizability of the AHA/ACC/HRS guidelines for Japanese patients with CS remains unclear. METHODS: This study examined 188 consecutive patients with CS in 2 tertiary hospitals between 1979 and 2020. Patients were followed for a primary outcome of VT/VF or SCD. RESULTS: During a median follow-up of 5.68 years, the primary outcome occurred in 44 patients (23%). Patients with a class I recommendation for ICD implantation showed the highest incidence of the primary outcome among patients in whom the guideline recommendations for ICD implantation were used (log-rank test; p = 0.03). However, compared with patients with left ventricular ejection fractions (LVEFs) ≤35%, there was no significant difference in the incidence of the primary outcome among patients with LVEFs >35% and those who required a permanent pacemaker (p = 0.31); similar results were observed in those with LVEFs >35% and late gadolinium enhancement during cardiovascular magnetic resonance imaging (p = 0.22). CONCLUSIONS: The American guideline recommendations for ICD implantation might be applicable to Japanese patients with CS. Implantation of an ICD may need to be considered in these patients if they require a permanent pacemaker or have late gadolinium enhancement, regardless of LVEF.
  • Keisuke Okuno, Yoshiro Naito, Masanori Asakura, Masataka Sugahara, Tetsuo Horimatsu, Seiki Yasumura, Saki Tahara, Toshiyuki Nagai, Yoshihiko Saito, Tsutomu Yoshikawa, Tohru Masuyama, Masaharu Ishihara, Toshihisa Anzai
    International journal of cardiology. Heart & vasculature 34 100796 - 100796 2021/06 
    Background: Anemia and chronic kidney disease (CKD) are common in patients with heart failure with preserved left ventricular fraction (HFpEF). However, it is entirely unknown about the impact of anemia on prognosis in HFpEF patients with CKD. In this study, we investigated the impact of anemia on prognosis and the optimal hemoglobin (Hb) levels to predict prognosis in HFpEF patients with CKD. Methods and Results: We prospectively examined 523 consecutive HFpEF patients enrolled in Japanese heart failure syndrome with preserved ejection fraction registry. CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 mL /min/1.73 m2. The prevalence rate of anemia was 78% in HFpEF patients with CKD by using the World Health Organization criteria. Kaplan-Meier analysis for all-cause mortality and heart failure rehospitalization demonstrated that anemic patients had poor prognosis compared with non-anemic patients in HFpEF patients with CKD, but not those without CKD. According to the degree of CKD, anemia affected prognosis in HFpEF patients with mild CKD (45 ≤ eGFR < 60), but not those with moderate to severe CKD (15 ≤ eGFR < 45). Additionally, multivariate analysis revealed that anemia and Hb levels were independent predictors of composite outcomes in HFpEF patients with mild CKD, but not those with moderate to severe CKD. Finally, survival classification and regression tree analysis showed that the optimal Hb levels to predict composite outcomes were 10.7 g/dL in those with mild CKD. Conclusions: Anemia has an impact on prognosis in HFpEF patients, especially among those with mild CKD.
  • Hirokazu Komoriyama, Kiwamu Kamiya, Yuta Kobayashi, Satonori Tsuneta, Takao Konishi, Takuma Sato, Hiroyuki Iwano, Toshiyuki Nagai, Satoru Wakasa, Kohsuke Kudo, Toshihisa Anzai
    Circulation journal : official journal of the Japanese Circulation Society 85 (6) 954 - 954 2021/05/25
  • Toshiyuki Nagai, Motoki Nakao, Toshihisa Anzai
    Circulation journal : official journal of the Japanese Circulation Society 85 (5) 576 - 583 2021/04/23 
    Clinical risk stratification is a key strategy used to identify low- and high-risk subjects to optimize the management, ranging from pharmacological treatment to palliative care, of patients with heart failure (HF). Using statistical modeling techniques, many HF risk prediction models that combine predictors to assess the risk of specific endpoints, including death or worsening HF, have been developed. However, most risk prediction models have not been well-integrated into the clinical setting because of their inadequacy and diverse predictive performance. To improve the performance of such models, several factors, including optimal sampling and biomarkers, need to be considered when deriving the models; however, given the large heterogeneity of HF, the currently advocated one-size-fits-all approach is not appropriate for every patient. Recent advances in techniques to analyze biological "omics" information could allow for the development of a personalized medicine platform, and there is growing awareness that an integrated approach based on the concept of system biology may be an excessively naïve view of the multiple contributors and complexity of an individual's HF phenotype. This review article describes the progress in risk stratification strategies and perspectives of emerging precision medicine in the field of HF management.
  • Toshihisa Anzai, Takuma Sato, Yoshihiro Fukumoto, Chisato Izumi, Yoshiyuki Kizawa, Masatoshi Koga, Katsuji Nishimura, Mitsuru Ohishi, Akihiro Sakashita, Yasushi Sakata, Tsuyoshi Shiga, Yasuchika Takeishi, Satoshi Yasuda, Kazuhiro Yamamoto, Takahiro Abe, Rie Akaho, Yasuhiro Hamatani, Hayato Hosoda, Naoki Ishimori, Mika Kato, Yoshiharu Kinugasa, Takuro Kubozono, Toshiyuki Nagai, Shogo Oishi, Katsuki Okada, Tatsuhiro Shibata, Atsushi Suzuki, Tsuyoshi Suzuki, Masahito Takagi, Yasuko Takada, Kenkichi Tsuruga, Akiomi Yoshihisa, Dai Yumino, Keiichi Fukuda, Yasuki Kihara, Yoshihiko Saito, Yoshiki Sawa, Hiroyuki Tsutsui, Takeshi Kimura
    Circulation journal : official journal of the Japanese Circulation Society 85 (5) 695 - 757 2021/04/23
  • Takahide Kadosaka, Toshiyuki Nagai, Shinya Suzuki, Ichiro Sakuma, Masaharu Akao, Takeshi Yamashita, Toshihisa Anzai, Ken Okumura
    Cardiovascular drugs and therapy 36 (4) 691 - 703 2021/04/08 
    PURPOSE: Although direct oral anticoagulants are effective and safe in preventing stroke in atrial fibrillation (AF) patients with low body weight, data remain limited in AF patients with extremely low body weight (<50 kg). We aimed to investigate the association of this body weight category with clinical outcomes in elderly AF patients receiving apixaban. METHODS: The J-ELD AF Registry is a large-scale, multicenter prospective observational study of Japanese non-valvular AF patients aged ≥ 75 years taking on-label doses of apixaban. The entire cohort (3025 patients from 110 institutions) was divided into three body weight subgroups: >60 kg (n = 1019, 33.7%), 50-60 kg (n = 1126, 37.2%), and <50 kg (n = 880, 29.1%). RESULTS: The event incidence rates (/100 person years) were 1.69, 1.82, and 1.23 for stroke or systemic embolism (P = 0.60); 1.37, 1.73, and 2.73 for bleeding requiring hospitalization (P = 0.154); 2.02, 2.67, and 4.92 for total death (P = 0.003); and 0.73, 0.95, and 1.23 for cardiovascular death (P = 0.57), respectively. After adjusting for confounders by Cox regression analysis, body weight <50 kg was not an independent risk for stroke or systemic embolism, bleeding requiring hospitalization, total death, or cardiovascular death. CONCLUSIONS: The incidence of events in each body weight group was comparable for stroke or systemic embolism and bleeding requiring hospitalization, and body weight <50 kg might not be an independent risk for death in Japanese non-valvular AF patients aged ≥ 75 years taking on-label doses of apixaban.
  • 佐藤 琢真, 永井 利幸, 安斉 俊久
    Heart View (株)メジカルビュー社 25 (4) 332 - 337 1342-6591 2021/04 
    ＜文献概要＞Point 1 身体的,社会的,精神・心理的,スピリチュアルな苦痛といった全人的苦痛に対応するには,多職種による連携を促進する必要がある。そのため,互いの役割や専門性を理解したうえで,協働することが可能な体制を整備する必要がある。2 循環器疾患における緩和ケアでは,疾患そのものに対する適切な治療が症状ならびにQOL改善のために必要であり,多職種が連携して行う循環器疾患患者の管理全体の流れのなかで提供されることが望ましい。3 治療抵抗性の症状管理や困難な意思決定支援やコミュニケーションなど,複雑な問題への対応には緩和ケア医の経験が必要となるため,専門的緩和ケアチームとの十分な連携が重要である。
  • 負荷心エコー図検査の現状と未来 負荷心エコー図検査を活かす 検査導入後5年間の取り組み
    辻永 真吾, 岩野 弘幸, 青柳 裕之, 玉置 陽生, 本居 昂, 石坂 傑, 千葉 泰之, 永井 利幸, 安斉 俊久
    超音波医学 (公社)日本超音波医学会 48 (Suppl.) S212 - S212 1346-1176 2021/04
  • 中尾 元基, 永井 利幸
    診断と治療 (株)診断と治療社 109 (13) 64 - 70 0370-999X 2021/03/24
  • 中尾 元基, 永井 利幸
    診断と治療 (株)診断と治療社 109 (Suppl.) 64 - 70 0370-999X 2021/03
  • 循環器疾患患者のこころの問題にどう向き合うか?(緩和ケアも含めて) 当院における心不全緩和ケアチームの立ち上げと現状
    阿部 隆宏, 佐藤 琢真, 加藤 美香, 笠谷 美鈴, 成田 尚, 福澤 宏之, 片山 真育, 池田 陽子, 小島 尚子, 杉本 由佳, 永井 利幸, 安斉 俊久
    日本循環器学会学術集会抄録集 (一社)日本循環器学会 85回 CS5 - 3 2021/03
  • 循環器疾患患者のこころの問題にどう向き合うか?(緩和ケアも含めて) 当院における心不全緩和ケアチームの立ち上げと現状
    阿部 隆宏, 佐藤 琢真, 加藤 美香, 笠谷 美鈴, 成田 尚, 福澤 宏之, 片山 真育, 池田 陽子, 小島 尚子, 杉本 由佳, 永井 利幸, 安斉 俊久
    日本循環器学会学術集会抄録集 (一社)日本循環器学会 85回 CS5 - 3 2021/03
  • Yoshifumi Mizuguchi, Takao Konishi, Toshiyuki Nagai, Tomoya Sato, Sakae Takenaka, Atsushi Tada, Yuta Kobayashi, Hirokazu Komoriyama, Yoshiya Kato, Kazunori Omote, Takuma Sato, Kiwamu Kamiya, Shingo Tsujinaga, Hiroyuki Iwano, Kenjiro Kikuchi, Shinya Tanaka, Toshihisa Anzai
    The American journal of emergency medicine 44 100 - 105 2021/02/05 
    OBJECTIVES: Although electrolyte abnormalities are related to worse clinical outcomes in patients with acute myocardial infarction (AMI), little is known about the association between admission serum magnesium level and adverse events in AMI patients complicated by out-of-hospital cardiac arrest presenting with malignant ventricular arrhythmias (OHCA-MVA). We investigated the prognostic value of serum magnesium level on admission in these patients. METHODS: We retrospectively analyzed the data of 165 consecutive reperfused AMI patients complicated with OHCA-MVA between April 2007 and February 2020 in our university hospital. Serum magnesium concentration was measured on admission. The primary outcome was in-hospital death. RESULTS: Fifty-four patients (33%) died during hospitalization. Higher serum magnesium level was significantly related to in-hospital death (Fine & Gray's test; p < 0.001). In multivariable logistic regression analyses, serum magnesium level on admission was independently associated with in-hospital death (hazard ratio 2.68, 95% confidence interval 1.24-5.80) even after adjustment for covariates. Furthermore, the incidences of cardiogenic shock necessitating an intra-aortic balloon pump (p = 0.005) or extracorporeal membrane oxygenation (p < 0.001), tracheal intubation (p < 0.001) and persistent vegetative state (p = 0.002) were significantly higher in patients with higher serum magnesium level than in those with lower serum magnesium level. CONCLUSIONS: In reperfused AMI patients complicated by OHCA-MVA, admission serum magnesium level might be a potential surrogate marker for predicting in-hospital death.
  • Hiroki Nakano, Yasuhiro Hamatani, Toshiyuki Nagai, Michikazu Nakai, Kunihiro Nishimura, Yoko Sumita, Hisao Ogawa, Toshihisa Anzai
    Scientific reports 11 (1) 1202 - 1202 2021/01/13 
    Although the risk of thromboembolism is increased in heart failure (HF) patients irrespective of atrial fibrillation (AF), especially during the acute decompensated phase, the effects of intravenous anticoagulants for these patients remain unclear. We sought to investigate the current practice and effects of intravenous anticoagulant therapy in acute HF (AHF) patients with sinus rhythm. We analyzed a nationwide prospective cohort from April 2012 to March 2016. We extracted 309,015 AHF adult patients. After application of the exclusion criteria, we divided the 92,573 study population into non-heparin [n = 70,621 (76.3%)] and heparin [n = 21,952 (23.7%)] groups according to the use of intravenous heparin for the first 2 consecutive days after admission. Multivariable logistic regression analyses demonstrated that heparin administration was not associated with in-hospital mortality (OR 0.97, 95% CI 0.91-1.03) and intracranial hemorrhage (OR 1.18, 95% CI 0.78-1.77), while heparin administration was significantly associated with increased incidence of ischemic stroke (OR 1.49, 95% CI 1.29-1.72) and venous thromboembolism (OR 1.62, 95% CI 1.14-2.30). In conclusion, intravenous heparin administration was not associated with favorable in-hospital outcomes in AHF patients with sinus rhythm. Routine additive use of intravenous heparin to initial treatment might not be recommended in AHF patients.
  • Kazunori Omote, Isao Yokota, Toshiyuki Nagai, Ichiro Sakuma, Yoshihisa Nakagawa, Kiwamu Kamiya, Hiroshi Iwata, Katsumi Miyauchi, Yukio Ozaki, Kiyoshi Hibi, Takafumi Hiro, Yoshihiro Fukumoto, Hiroyoshi Mori, Seiji Hokimoto, Yasuo Ohashi, Hiroshi Ohtsu, Hisao Ogawa, Hiroyuki Daida, Satoshi Iimuro, Hiroaki Shimokawa, Yasushi Saito, Takeshi Kimura, Masunori Matsuzaki, Ryozo Nagai, Toshihisa Anzai
    Journal of atherosclerosis and thrombosis 29 (1) 50 - 68 2021/01/09 
    AIM: The association between high-density lipoprotein cholesterol (HDL-C) level after statin therapy and cardiovascular events in patients with stable coronary artery disease (CAD) remains unclear. Thus, in this study, we sought to determine how HDL-C level after statin therapy is associated with cardiovascular events in stable CAD patients. METHODS: From the REAL-CAD study which had shown the favorable prognostic effect of high-dose pitavastatin in stable CAD patients with low-density lipoprotein cholesterol (LDL-C) ＜120 mg/dL, 9,221 patients with HDL-C data at baseline and 6 months, no occurrence of primary outcome at 6 months, and reported non-adherence for pitavastatin, were examined. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission after 6 months of randomization. Absolute difference and ratio of HDL-C levels were defined as (those at 6 months-at baseline) and (absolute difference/baseline)×100, respectively. RESULTS: During a median follow-up period of 4.0 (IQR 3.2-4.7) years, the primary outcome occurred in 417 (4.5%) patients. The adjusted risk of all HDL-C-related variables (baseline value, 6-month value, absolute, and relative changes) for the primary outcome was not significant (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.91-1.08, HR 1.03, 95% CI 0.94-1.12, HR 1.05, 95% CI 0.98-1.12, and HR 1.08, 95% CI 0.94-1.24, respectively). Furthermore, adjusted HRs of all HDL-C-related variables remained non-significant for the primary outcome regardless of on-treatment LDL-C level at 6 months. CONCLUSIONS: After statin therapy with modestly controlled LDL-C, HDL-C level has little prognostic value in patients with stable CAD.
  • Takao Konishi, Kohei Saiin, Youji Tamaki, Hiroyuki Natsui, Tomoya Sato, Sakae Takenaka, Atsushi Tada, Yoshifumi Mizuguchi, Yuta Kobayashi, Hirokazu Komoriyama, Yoshiya Kato, Takuma Sato, Rui Kamada, Kiwamu Kamiya, Toshiyuki Nagai, Shinya Tanaka, Toshihisa Anzai
    Cardiology journal 28 (5) 794 - 795 2021
  • Sakae Takenaka, Takao Konishi, Tomoya Sato, Atsushi Tada, Takuya Koizumi, Yoshifumi Mizuguchi, Takahide Kadosaka, Ko Motoi, Yuta Kobayashi, Hirokazu Komoriyama, Yoshiya Kato, Miwa Sarashina, Kazunori Omote, Shingo Tsujinaga, Takuma Sato, Rui Kamada, Kiwamu Kamiya, Hiroyuki Iwano, Toshiyuki Nagai, Tatsuya Orimo, Hirofumi Kamachi, Akinobu Taketomi, Toshihisa Anzai
    Case reports in cardiology 2021 5460816 - 5460816 2021 
    Acute myocardial infarction (AMI) caused by severe stenosis of left main coronary artery (LMCA) presenting with cardiogenic shock and pulmonary edema during noncardiac surgery is uncommon, but a catastrophic event. A 77-year-old male with cholangiocarcinoma underwent hepatectomy. During the surgery, he presented with cardiogenic shock, which did not respond to infusion administration or vasopressor. A transesophageal echocardiogram revealed anterior, septal, and lateral severe hypokinesia and impaired left ventricular function. Emergent coronary angiogram showed severe stenosis of LMCA. The patient underwent primary percutaneous coronary intervention (PCI) under the support of intra-aortic balloon pump, followed by extracorporeal membrane oxygenation. The chest roentgenogram showed pulmonary edema. Two days after PCI, he successfully underwent hepatectomy and bile duct resection. Early identification of the cause of hemodynamic instability during noncardiac surgery and invasive strategy are important for minimizing the myocardial injury and improving clinical outcomes in AMI of LMCA.
  • Yasuyuki Chiba, Hiroyuki Iwano, Sanae Kaga, Mio Shinkawa, Michito Murayama, Hiroshi Ohira, Suguru Ishizaka, Miwa Sarashina, Shingo Tsujinaga, Shinobu Yokoyama, Masahiro Nakabachi, Hisao Nishino, Kazunori Okada, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    Pulmonary Circulation 11 (1) 204589402098372 - 204589402098372 2045-8940 2021/01 
    Evaluation of left ventricular filling pressure plays an important role in the clinical management of pulmonary hypertension. However, the accuracy of echocardiographic parameters for the determination of left ventricular filling pressure in the presence of pulmonary vascular lesions has not been fully addressed. We retrospectively investigated 124 patients with pulmonary hypertension due to pulmonary vascular lesions (noncardiac pulmonary hypertension group) and 113 patients with ischemic heart disease (control group) who underwent right heart catheterization and echocardiography. The noncardiac pulmonary hypertension group was subdivided into less-advanced and advanced groups according to median pulmonary vascular resistance. Pulmonary artery wedge pressure was determined as left ventricular filling pressure. As echocardiographic parameters of left ventricular filling pressure, the ratio of early- (E) to late-diastolic transmitral flow velocity (E/A), ratio of E to early-diastolic mitral annular velocity (E/e′), and left atrial volume index were measured. In the less-advanced noncardiac pulmonary hypertension and control groups, positive correlations were observed between pulmonary artery wedge pressure and late-diastolic transmitral flow velocity ( R = 0.41, P = 0.002 and R = 0.71, P < 0.001, respectively) and left atrial volume index ( R = 0.53, P < 0.001 and R = 0.41, P < 0.001), whereas in the advanced noncardiac pulmonary hypertension group, pulmonary artery wedge pressure was only correlated with left atrial volume index ( R = 0.27, P = 0.032). In the controls, only pulmonary artery wedge pressure determined E (β = 0.48, P < 0.001), whereas both pulmonary artery wedge pressure and pulmonary vascular resistance were independent determinants of E (β = 0.29, P < 0.001 and β = –0.28, P = 0.001, respectively) in the noncardiac pulmonary hypertension group. In conclusion, in the presence of advanced pulmonary vascular lesions, conventional echocardiographic parameters may not accurately reflect left ventricular filling pressure. Elevated pulmonary vascular resistance would lower the E, even when pulmonary artery wedge pressure is elevated, resulting in blunting of echocardiographic parameters for the detection of elevated left ventricular filling pressure.
  • Yasuyuki Chiba, Hiroyuki Iwano, Michito Murayama, Sanae Kaga, Ko Motoi, Suguru Ishizaka, Shingo Tsujinaga, Asuka Tanemura, Shinobu Yokoyama, Masahiro Nakabachi, Hisao Nishino, Kazunori Okada, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography 34 (6) 690 - 692 2020/12/28
  • Hirokazu Komoriyama, Kazunori Omote, Toshiyuki Nagai, Yoshiya Kato, Nobutaka Nagano, Kazuhiro Koyanagawa, Kiwamu Kamiya, Takao Konishi, Takuma Sato, Yuta Kobayashi, Shingo Tsujinaga, Hiroyuki Iwano, Kengo Kusano, Satoshi Yasuda, Hisao Ogawa, Hatsue Ishibashi-Ueda, Toshihisa Anzai
    International journal of cardiology 321 113 - 117 2020/12/15 [Refereed][Not invited]
     
    BACKGROUND: The histopathological diagnosis of cardiac sarcoidosis (CS) is challenging because of sampling error in endomyocardial biopsy (EMB) and the determinants of positive EMB are unclear. Reduced left ventricular ejection fraction (LVEF) is a simple parameter of the extent of myocardial damage, and higher serum angiotensin-converting enzyme (ACE) activity would indicate the spread of disease activity in CS patients. Thus, we sought to examine whether these parameters are related to the histopathological diagnosis of CS by EMB. METHODS: A total of 94 consecutive clinically diagnosed CS patients between August 1986 and March 2019 who were admitted to two academic hospitals were examined. We determined EMB as positive if non-caseating epithelioid granulomas were confirmed in the myocardial tissue. Patients were divided into two groups according to positive (n = 37) and negative (n = 57) EMB. We assessed the relationship between LVEF, serum ACE activity and positive EMB. RESULTS: Multivariable analysis revealed that both LVEF and serum ACE were independently associated with positive EMB (OR 0.83, 95% CI 0.70-0.99; OR 1.39, 95% CI 1.02-1.90, respectively). Moreover, patients with both lower LVEF (<37%, median) and higher ACE activity (≥13.5 IU/L, median) had the highest frequency of positive EMB (p = .003). The combination of lower LVEF and higher serum ACE showed better specificity (91.2%) and positive predictive value (73.7%) than either LVEF or serum ACE alone for positive EMB. CONCLUSIONS: Lower LVEF and higher serum ACE activity were associated with positive EMB, suggesting that these parameters might be useful for predicting positive EMB in CS patients.
  • Tomoya Sato, Rui Kamada, Takuya Koizumi, Sakae Takenaka, Atsushi Tada, Shingo Tsujinaga, Takao Konishi, Takuma Sato, Masaya Watanabe, Toshiyuki Nagai, Toshihisa Anzai
    The Canadian journal of cardiology 36 (12) 1977.e1-1977.e3  2020/12 [Refereed][Not invited]
     
    Neuraxial modulation therapies, such as stellate ganglion block, thoracic epidural anaesthesia, and cardiac sympathetic denervation, are effective for ventricular arrhythmias. However, these treatments can increase the risk of bleeding and infection. In this case report, stellate ganglion phototherapy was safely and effectively performed for refractory ventricular tachycardias in a patient with a history of left ventricular assist device implantation. Stellate ganglion phototherapy may have the potential to treat refractory ventricular arrhythmias as an additive therapy or bridge therapy.
  • Toshikazu D Tanaka, Toshiyuki Nagai, Tomohisa Nagoshi, Michihiro Yoshimura
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 27 (6) 2149 - 2153 1071-3581 2020/12 [Refereed][Not invited]
     
    We present a case of a 42-year-old Japanese man with ocular and pulmonary sarcoidosis who eventually led to a diagnosis with cardiac sarcoidosis (CS) through endomyocardial biopsy (EMB), despite negative findings on both late gadolinium enhancement with cardiac magnetic resonance (LGE-CMR) imaging and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Cardiac sarcoidosis (CS) develops in only 5% of patients with systemic sarcoidosis. Previous studies have reported that CS was found in up to 50% of autopsy series with fatal sarcoidosis, implying that CS is frequently underdiagnosed with potentially life-threatening consequences. Therefore, the diagnostic accuracy and prognostic value of CS are important. Currently, LGE-CMR and FDG-PET play an important role in establishing a diagnosis of CS with high sensitivity. In the presented case, regardless of serial examinations with LGE-CMR and FDG-PET, confirmed diagnosis of CS could not be achieved; ultimately, a definitive diagnosis of CS was obtained through EMB. To the best of our knowledge, this is the first reported case showing the diagnosis of CS despite negative findings on serial LGE-CMR and FDG-PET examinations.
  • Tomonari Harada, Masaru Obokata, Kazunori Omote, Hiroyuki Iwano, Takahiro Ikoma, Kenya Okada, Kuniko Yoshida, Toshimitsu Kato, Koji Kurosawa, Toshiyuki Nagai, Kazuaki Negishi, Toshihisa Anzai, Masahiko Kurabayashi
    European heart journal cardiovascular Imaging 2020/11/07 
    AIMS: This study sought to determine the independent and incremental prognostic value of semiquantitative measures of tricuspid regurgitation (TR) severity over right heart remodelling and pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Echocardiography was performed on 311 HFpEF patients. TR severity was defined by the semiquantitative measures [i.e. vena contracta width (VCW) and jet area] and by the guideline-based integrated qualitative approach (absent, mild, moderate, or severe). All-cause mortality or heart failure hospitalization occurred in 101 patients over a 2.1-year median follow-up. There was a continuous association between TR severity and the composite outcome with a hazard ratio (HR) of 1.17 per 1 mm increase of VCW [95% confidence interval (CI) 1.08-1.26, P < 0.0001]. Compared with patients with the lowest VCW category (≤1 mm), RV-adjusted HRs for the outcome were 1.99 (95% CI 1.05-3.77), 2.63 (95% CI 1.16-5.95), and 5.00 (95% CI 1.60-15.7) for 1-3, 3-7, and ≥7 mm VCW categories, respectively. TR severity as defined by the guideline-based approach showed a similarly graded association, but it was no longer significant in models including PH. In contrast, VCW remained independently and incrementally associated with the outcome after adjusting for established prognostic factors, as well as RV diameter and PH (fully adjusted HR 1.14 per 1 mm, 95% CI 1.02-1.27, P = 0.02; χ2 58.8 vs. 51.5, P = 0.03). CONCLUSION: The current data highlight the potential value of the semiquantitative measures of TR severity for the risk stratification in patients with HFpEF.
  • 経カテーテル的大動脈弁置換術による左室機能の変化と左室外的仕事量との関連
    辻永 真吾, 岩野 弘幸, 石坂 傑, 千葉 泰之, 更科 美羽, 中鉢 雅大, 神谷 究, 永井 利幸, 安斉 俊久
    超音波医学 (公社)日本超音波医学会 47 (Suppl.) S208 - S208 1346-1176 2020/11
  • Yasuyuki Shiraishi, Shun Kohsaka, Takayuki Abe, Toshiyuki Nagai, Ayumi Goda, Yosuke Nishihata, Yuji Nagatomo, Mike Saji, Yuichi Toyosaki, Makoto Takei, Takeshi Kitai, Takashi Kohno, Keiichi Fukuda, Yuya Matsue, Toshihisa Anzai, Tsutomu Yoshikawa
    Journal of clinical medicine 9 (11) 2020/10/23 
    Early and rapid risk stratification of patients with acute heart failure (AHF) is crucial for appropriate patient triage and outcome improvements. We aimed to develop an easy-to-use, in-hospital mortality risk prediction tool based on data collected from AHF patients at their initial presentation. Consecutive patients' data pertaining to 2006-2017 were extracted from the West Tokyo Heart Failure (WET-HF) and National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure (NaDEF) registries (n = 4351). Risk model development involved stepwise logistic regression analysis and prospective validation using data pertaining to 2014-2015 in the Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure Syndrome (REALITY-AHF) (n = 1682). The final model included data describing six in-hospital mortality risk predictors, namely, age, systolic blood pressure, blood urea nitrogen, serum sodium, albumin, and natriuretic peptide (SOB-ASAP score), available at the time of initial triage. The model showed excellent discrimination (c-statistic = 0.82) and good agreement between predicted and observed mortality rates. The model enabled the stratification of the mortality rates across sixths (from 14.5% to <1%). When assigned a point for each associated factor, the integer score's discrimination was similar (c-statistic = 0.82) with good calibration across the patients with various risk profiles. The models' performance was retained in the independent validation dataset. Promptly determining in-hospital mortality risks is achievable in the first few hours of presentation; they correlate strongly with mortality among AHF patients, potentially facilitating clinical decision-making.
  • 小森山 弘和, 表 和徳, 永井 利幸, 加藤 喜哉, 永野 伸卓, 神谷 究, 小西 崇夫, 草野 研吾, 植田 初江, 安斉 俊久
    日本サルコイドーシス/肉芽腫性疾患学会雑誌 日本サルコイドーシス 40 (サプリメント号) 52 - 52 1883-1273 2020/10
  • 小林 雄太, 永井 利幸, 神谷 究, 小西 崇夫, 佐藤 琢真, 加藤 喜哉, 小森山 弘和, 草野 研吾, 植田 初江, 安斉 俊久
    日本サルコイドーシス/肉芽腫性疾患学会雑誌 日本サルコイドーシス 40 (サプリメント号) 56 - 56 1883-1273 2020/10
  • 萩原 光, 渡邉 昌也, 中尾 元基, 甲谷 太郎, 小林 雄太, 加藤 喜哉, 小森山 弘和, 鎌田 塁, 永井 利幸, 安斉 俊久
    日本サルコイドーシス/肉芽腫性疾患学会雑誌 日本サルコイドーシス 40 (サプリメント号) 56 - 56 1883-1273 2020/10
  • 【循環器疾患のPrecision Medicine】臨床 心不全個別化医療
    永井 利幸, 安斉 俊久
    Cardiac Practice (株)メディカルレビュー社 31 (1) 32 - 36 0915-874X 2020/10
  • Yasuyuki Chiba, Kiwamu Kamiya, Tadao Aikawa, Hiroyuki Iwano, Toshiyuki Nagai, Takahiro Ishigaki, Yasushige Shingu, Ai Shimizu, Yoshiro Matsui, Toshihisa Anzai
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 27 (5) 1841 - 1843 1071-3581 2020/10 [Refereed][Not invited]
  • Takahide Kadosaka, Shingo Tsujinaga, Hiroyuki Iwano, Kiwamu Kamiya, Azusa Nagai, Yoshifumi Mizuguchi, Ko Motoi, Kazunori Omote, Toshiyuki Nagai, Ichiro Yabe, Toshihisa Anzai
    ESC heart failure 2020/09/11 
    Anti-mitochondrial antibody (AMA)-positive myositis is an atypical inflammatory myopathy characterized by chronic progressive respiratory muscle weakness, muscular atrophy, and cardiac involvement. Arrhythmias, cardiomyopathy, and myocarditis have been reported as cardiac manifestations. Herein, we present the first report of a patient diagnosed with having AMA-positive myositis with cardiac involvement mimicking cardiac sarcoidosis.
  • Kazuhiro Koyanagawa, Yuta Kobayashi, Tadao Aikawa, Atsuhito Takeda, Hideaki Shiraishi, Satonori Tsuneta, Noriko Oyama-Manabe, Hiroyuki Iwano, Toshiyuki Nagai, Toshihisa Anzai
    Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine 20 (3) 320 - 324 2020/09/07 
    To assess myocardial fibrosis associated with muscular dystrophy, T1-mapping and extracellular volume fraction (ECV) quantification was prospectively performed using cardiovascular MR (CMR) imaging in 6 male patients with muscular dystrophy and 5 female putative carriers of Duchenne or Becker muscular dystrophy. Five patients and all putative carriers had an elevated ECV (>29.5% for men and >35.2% for women), suggesting that ECV has a potential to detect diffuse fibrotic changes in patients and putative carriers of muscular dystrophy.
  • Nozomi Niimi, Mitsuaki Sawano, Nobuhiro Ikemura, Toshiyuki Nagai, Shintaro Nakano, Satoshi Shoji, Yasuyuki Shiraishi, Ikuko Ueda, Yohei Numasawa, Masahiro Suzuki, Shigetaka Noma, Keiichi Fukuda, Shun Kohsaka
    Journal of clinical medicine 9 (9) 2020/09/07 
    In the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial, an early invasive strategy did not decrease mortality compared to a conservative strategy for stable ischemic heart disease (SIHD) patients with moderate-to-severe ischemia, and the role of revascularization would be revised. However, the applicability and potential influence of this trial in daily practice remains unclear. Our objective was to assess the eligibility and representativeness of the ISCHEMIA trial on the patients with percutaneous coronary intervention (PCI). From a multicenter registry, we extracted a consecutive 13,223 SIHD patients with PCI (baseline cohort). We applied ISCHEMIA eligibility criteria and compared the baseline characteristics between the eligible patients and the actual study participants (randomized controlled trial (RCT) patients). In 3463 patients with follow-up information (follow-up cohort), the 2 year composite of major adverse cardiac events was evaluated between the eligible patients and RCT patients, as well as eligible and non-eligible patients in the registry. In the baseline cohort, 77.3% of SIHD patients with moderate-to-severe ischemia were eligible for the ISCHEMIA. They were comparable with RCT patients for baseline characteristics and outcomes unlike the non-eligible patients. In conclusion, the trial results seem applicable for the majority of PCI patients with moderate-to-severe ischemia except for the non-eligible patients.
  • Yoshiya Kato, Toshiyuki Nagai, Noriko Oyama-Manabe, Satonori Tsuneta, Michikazu Nakai, Yuta Kobayashi, Hirokazu Komoriyama, Kazunori Omote, Shingo Tsujinaga, Takuma Sato, Takao Konishi, Kiwamu Kamiya, Hiroyuki Iwano, Toshihisa Anzai
    JACC. Cardiovascular imaging 13 (9) 2050 - 2052 2020/09 [Refereed][Not invited]
  • Shingo Tsujinaga, Hiroyuki Iwano, Tomohiro Oshino, Takahide Kadosaka, Yoshifumi Mizuguchi, Ko Motoi, Yasuyuki Chiba, Taro Koya, Taro Temma, Kiwamu Kamiya, Arata Fukushima, Takuya Koizumi, Tomoya Sato, Sakae Takenaka, Atsushi Tada, Suguru Ishizaka, Miwa Sarashina, Kazunori Omote, Rui Kamada, Takao Konishi, Takuma Sato, Toshiyuki Nagai, Hiroko Yamashita, Toshihisa Anzai
    Internal medicine (Tokyo, Japan) 59 (17) 2155 - 2160 2020/09/01 [Refereed][Not invited]
     
    Epirubicin-based chemotherapy carries a risk of inducing heart failure, although the frequency is rare. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, has recently been widely used in patients with recurrent breast cancer as a first-line chemotherapeutic agent. Heart failure or arterial thromboembolism has been reported as a rare cardiovascular complication of bevacizumab. We herein report a breast cancer patient with reversible cancer therapeutics-related cardiac dysfunction associated with bevacizumab and epirubicin complicating intracardiac thrombi in the left atrium and left ventricle. This case underscores the importance of tailored medical planning according to the individual status in patients receiving anti-cancer therapies.
  • 肺動静脈奇形に対し卵円孔経由で経静脈的塞栓術を施行した1例
    阿保 大介, 曽山 武士, 永井 利幸, 森田 亮, 吉野 裕紀, 木野田 直也, 工藤 與亮
    日本インターベンショナルラジオロジー学会雑誌 (一社)日本インターベンショナルラジオロジー学会 35 (Suppl.) 216 - 216 1340-4520 2020/08
  • Masayoshi Oikawa, Akiomi Yoshihisa, Yu Sato, Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Kazuhiro Yamamoto, Yasuchika Takeishi, Toshihisa Anzai
    Heart and vessels 35 (8) 1087 - 1094 2020/08 [Refereed][Not invited]
     
    A growing body of evidence suggests that mitral regurgitation (MR) is associated with higher mortality in heart failure patients with reduced ejection fraction. However, prognostic impact of MR on heart failure patients with preserved ejection fraction (HFpEF) has not been fully examined. The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese hospitalized HFpEF patients with LVEF ≥ 50%. Severe valvular heart disease was excluded from this cohort. We divided the consecutive 341 patients into two groups based on the severity of MR at discharge: no or mild MR group (n = 317) and moderate MR group (n = 24). Compared with no or mild MR group, moderate MR group showed larger left ventricular end-diastolic diameter (52 [48-59] vs. 46 [42-50] mm, P < 0.001), left ventricular systolic diameter (35 [30-37] vs. 29 [26-34] mm, P = 0.006), left atrial diameter (49 [46-56] vs. 45 [40-50] mm, P < 0.001), and higher tricuspid regurgitation peak gradient (33 [25-40] vs. 27 [21-33] mmHg, P = 0.012). In contrast, levels of plasma B-type natriuretic peptide and left ventricular ejection fraction were comparable between the two groups. In the follow-up period (median 738 days), there were 57 all-cause deaths. In the Kaplan-Meier analysis, all-cause mortality was higher in moderate MR group than in no or mild MR group (log-rank P = 0.023). In the Cox proportional hazard analysis, moderate MR at discharge was a predictor of all-cause mortality (hazard ratio 2.256, 95% confidence interval 1.035-4.917, P = 0.041). Moderate MR at discharge is associated with adverse prognosis in hospitalized patients with HFpEF.
  • Hiroyuki Iwano, Shinobu Yokoyama, Kiwamu Kamiya, Toshiyuki Nagai, Shingo Tsujinaga, Miwa Sarashina, Suguru Ishizaka, Yasuyuki Chiba, Masahiro Nakabachi, Hisao Nishino, Michito Murayama, Kazunori Okada, Sanae Kaga, Toshihisa Anzai
    Heart and vessels 35 (8) 1079 - 1086 2020/08 [Refereed][Not invited]
     
    BACKGROUND: A v wave on pulmonary artery wedge (PAW) pressure sometimes augments and appears on pulmonary artery (PA) pressure wave in patients with heart failure (HF). However, the significance of PA v wave in HF remains to be elucidated. METHODS: We retrospectively analyzed pressure waveforms in 61 HF patients (left ventricular ejection fraction 35 ± 15%). On the PAW and PA pressure waveforms, mean pressure as well as peak and amplitude of v waves (ampPAWv and ampPAv, respectively) were measured. Occurrence of worsening HF and cardiac death was recorded for 2 years after the catheterization. RESULTS: The ampPAWv did not correlate with ampPAv. When the patients were divided into 4 groups: I (high-ampPAWv/high-ampPAv), II (high-ampPAWv/low-ampPAv), III (low-ampPAWv/high-ampPAv), and IV (low-ampPAWv/low-ampPAv), the prevalence of group III was low (I: 13, II: 17, III: 4, IV: 27). Mean pressures of PAW and PA were similarly elevated in groups I and II. Cardiac index was lowest (I: 2.0 ± 0.4, II: 2.8 ± 0.6, III: 2.2 ± 0.2, IV: 2.4 ± 0.6 L/min/m2, ANOVA P < 0.01, P < 0.01 for I vs II) and tricuspid annular plane systolic excursion / systolic PA pressure was impaired (I: 0.27 ± 0.07, II: 0.48 ± 0.22, III: 0.59 ± 0.35, IV: 0.68 ± 0.35 mm/mmHg, ANOVA P < 0.01) in group I. During the follow-up, 13 events were observed. Kaplan-Meier analysis showed that patients in group I were at highest risk of cardiac events. CONCLUSIONS: PA v was observed mainly in patients with augmented PAW v wave and decreased cardiac index, suggesting an advanced stage of HF. Moreover, augmented PAv was associated with worse outcome in HF patients.
  • Hiroki Nakano, Toshiyuki Nagai, Yasuyuki Honda, Satoshi Honda, Naotsugu Iwakami, Chisa Matsumoto, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Hisao Ogawa, Satoshi Yasuda, Taishiro Chikamori, Toshihisa Anzai
    European heart journal. Acute cardiovascular care 9 (5) 399 - 405 2020/08 [Refereed][Not invited]
     
    BACKGROUND: Acid-base balance can change as a result of pulmonary oedema and low tissue perfusion in acute heart failure patients. However, its long-term prognostic significance remains to be clarified. METHODS: We prospectively examined a cohort of 472 consecutive acute heart failure patients who underwent arterial blood gas analysis on admission between January 2013 and May 2016. Acidaemia, alkalaemia and normal range of base excess were defined as pH <7.38, >7.42 and -2 to 2 mEq/L, respectively. The primary outcome was all-cause death. RESULTS: During a median follow-up period of 714 days, 101 patients died. Although there was no difference in mortality among patients with acidaemia, normal pH and alkalaemia (p = 0.92), patients with high base excess had the highest mortality compared with others. Multivariable Cox proportional hazard models revealed that high base excess was an independent determinant of mortality (hazard ratio 1.83, 95% confidence interval 1.08-3.13 (high versus normal base excess), hazard ratio 0.81, 95% confidence interval 0.47-1.41 (low versus normal base excess)), even after adjustment for significant prognostic covariates. Furthermore, regarding mortality stratified by base excess and carbon dioxide partial pressure (pCO2), patients with high base excess (>2.1 mEq/L) and high pCO2 (>40 mmHg) had the highest mortality compared with others. CONCLUSIONS: High base excess, but not low base excess, on admission was associated with long-term mortality in acute heart failure patients, indicating the importance of evaluating acid-base balance on admission by base excess for stratifying the risk of mortality in patients with acute heart failure.
  • Sayaka Funabashi, Kazunori Omote, Toshiyuki Nagai, Yasuyuki Honda, Hiroki Nakano, Satoshi Honda, Naotsugu Iwakami, Yasuhiro Hamatani, Michikazu Nakai, Kunihiro Nishimura, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
    European heart journal. Acute cardiovascular care 9 (5) 429 - 436 2020/08 [Refereed][Not invited]
     
    BACKGROUND: The prognostic significance of urinary N-acetyl-β-D-glucosamidase in acute heart failure has not been fully elucidated. Accordingly, this study investigated whether urinary N-acetyl-β-D-glucosamidase could be associated with subsequent adverse events in acute heart failure patients. METHODS: We studied 708 consecutive acute heart failure patients who had accessible N-acetyl-β-D-glucosamidase data on admission from the National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure registry. We assessed the relationship between the admission N-acetyl-β-D-glucosamidase level and the combined endpoint of all-cause death and worsening heart failure. Worsening heart failure was defined as worsening symptoms and signs of heart failure requiring intensification of intravenous therapy such as diuretics, vasodilators and inotropes or initiation of mechanical support after stabilisation with initial treatment during hospitalisation, or readmission due to heart failure after discharge. RESULTS: During a median follow-up period of 763 (interquartile range 431-1028) days, higher urinary N-acetyl-β-D-glucosamidase was significantly related to increased events of all-cause death and worsening heart failure. In addition, patients with higher urinary N-acetyl-β-D-glucosamidase and lower estimated glomerular filtration rate on admission had the worst clinical outcomes. In multivariable Cox regression, urinary N-acetyl-β-D-glucosamidase on admission was independently associated with adverse events (hazard ratio 1.19, 95% confidence interval 1.04-1.35) even after adjustment by covariates including the baseline estimated glomerular filtration rate. CONCLUSIONS: Higher urinary N-acetyl-β-D-glucosamidase level on admission was independently associated with worse clinical outcomes. Our findings indicate the potential value of assessing urinary N-acetyl-β-D-glucosamidase on admission for further risk stratification in patients with acute heart failure.
  • Atsushi Tada, Kazunori Omote, Toshiyuki Nagai, Yasuyuki Honda, Hiroki Nakano, Satoshi Honda, Naotsugu Iwakami, Yasuhiro Hamatani, Michikazu Nakai, Kunihiro Nishimura, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
    Journal of clinical medicine 9 (7) 2020/07/13 [Refereed][Not invited]
     
    The prognostic impact of hospital-acquired pneumonia (HAP) in acute heart failure (AHF) patients have not been fully elucidated. We evaluated 776 consecutive hospitalized AHF patients. The primary in-hospital outcomes were all-cause death and worsening heart failure (WHF), while the outcome following discharge was all-cause death. The clinical diagnosis of HAP was based on clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Patients with HAP had a significantly higher incidence of in-hospital death (12% vs. 1%, p < 0.001), WHF during the hospitalization (28% vs. 7%, p < 0.001), and longer length of hospital stay (p = 0.003) than those without. Among patients who survived at discharge, during a median follow-up period of 741 (interquartile range 422-1000) days, the incidence of all-cause death was significantly higher in patients with HAP than in those without (p < 0.001). In the multivariable Cox regression, HAP development was independently associated with all-cause death after discharge (HR [hazard ratio] 1.86, 95%CI [confidence interval] 1.08-3.19). Furthermore, older age (OR [odds ratio] 1.04, 95%CI 1.01-1.08), male sex (OR 2.21, 95%CI 1.14-4.28), and higher serum white blood cell count (OR 1.18, 95%CI 1.09-1.29) and serum C-reactive protein (OR 1.08, 95%CI 1.01-1.06) were independently associated with HAP development. In hospitalized patients with AHF, HAP development was associated with worse clinical outcomes, suggesting the importance of prevention and early screening for HAP.
  • 心不全と栄養 心不全患者の栄養状態評価と集学的アプローチの重要性(The Importance of Assessing Nutritional Status and Multidisciplinary Approach for Malnutrition in Patients with Heart Failure)
    永井 利幸, 安斉 俊久
    日本循環器学会学術集会抄録集 84回 シンポジウム19 - 1 2020/07
  • Taro Koya, Taro Temma, Masaya Watanabe, Rui Kamada, Toshiyuki Nagai, Toshihisa Anzai
    HeartRhythm case reports 6 (7) 411 - 414 2020/07 [Refereed][Not invited]
  • Osamu Manabe, Noriko Oyama-Manabe, Toshiyuki Nagai, Sho Furuya, Toshihisa Anzai
    European journal of nuclear medicine and molecular imaging 47 (7) 1773 - 1774 1619-7070 2020/07 [Refereed][Not invited]
  • Tetsuo Yamaguchi, Michikazu Nakai, Yoko Sumita, Kunihiro Nishimura, Toshihiro Nozato, Takashi Ashikaga, Toshiyuki Nagai, Toshihisa Anzai, Yasushi Sakata, Hitoshi Ogino
    Journal of vascular surgery 71 (6) 1907 - 1912 0741-5214 2020/06 [Refereed][Not invited]
     
    OBJECTIVE: This study aimed to assess the sex differences in clinical presentation and outcomes of Japanese patients with ruptured aortic aneurysm (rAA) using a large nationwide claims-based database in Japan. METHODS: We identified patients hospitalized in certified teaching hospitals in Japan with rAA between April 1, 2012, and March 31, 2015. Patients' characteristics and in-hospital outcomes were compared between men and women. The Barthel index was used for evaluating functional status at discharge by examining the ability to perform basic daily activities. RESULTS: Of 7086 eligible patients, 32.3% (2291/7086) were women. Women were older than men (81.9 years vs 76.1 years; P < .001), had higher prevalence of coma at admission (33.2% vs 25.2%; P < .001), and were less likely to undergo emergency operation including endovascular aneurysm repair (35.7% vs 51.1%; P < .001). The unadjusted mortality rate (62.5% vs 52.0%; P < .001) and Barthel index at discharge (78.7 vs 86.1; P < .001) were significantly worse in women than in men. However, multilevel mixed-effect logistic regression analyses showed that female sex itself was not an independent predictor for in-hospital death (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.78-1.04; P = .17). Older age, coma at admission, and vasopressor use were detected as independent predictors for in-hospital death. The same results were confirmed for each rupture site. Stratified analyses showed that older women (threshold, 80 years; OR, 0.81; 95% CI, 0.66-0.98; P = .028) and those who underwent emergency operation (OR, 0.75; 95% CI, 0.61-0.93; P = .009) showed significantly better outcomes than men. CONCLUSIONS: In a univariate analysis, female patients with rAA showed worse mortality than men because of their older age, more severe clinical presentation, and low emergency operation rate. However, after adjustment for covariates, female sex itself was not associated with increased mortality.
  • Tadao Aikawa, Kyohei Yamaji, Toshiyuki Nagai, Shun Kohsaka, Kiwamu Kamiya, Kazunori Omote, Taku Inohara, Yohei Numasawa, Kenichi Tsujita, Tetsuya Amano, Yuji Ikari, Toshihisa Anzai
    Journal of the American Heart Association 9 (9) e015404  2020/05/05 [Refereed][Not invited]
     
    Background There is a limited evidence base to support the volume-outcome relationship in patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery disease (UPLMD). This study aimed to evaluate the relationship between institutional and operator volume and in-hospital outcomes in patients undergoing PCI for unprotected left main coronary artery disease. Methods and Results We analyzed characteristics and clinical outcomes of 24 320 patients undergoing PCI for unprotected left main coronary artery disease at 1102 hospitals by 7244 operators using data from the Japanese nationwide J-PCI Registry (National PCI Data Registry) between January 2014 and December 2017. We classified institutions and operators into quartiles based on the mean annual volume of PCI. A generalized linear mixed-effects model was used to evaluate the association between institutional and operator PCI volume and in-hospital outcomes. Among the 24 320 patients, 4027 (16.6%), 6147 (25.3%), and 14 146 (58.2%) presented with ST-segment-elevation myocardial infarction, non-ST-segment-elevation acute coronary syndrome, and stable ischemic heart disease; their crude in-hospital mortality was 15%, 3.1%, and 0.3%, respectively. Compared with patients in the lowest quartile of institutional volume (1-216 PCIs/y), the adjusted odds ratio of in-hospital death in patients in the second (217-323 PCIs/y), third (324-487 PCIs/y), and fourth (488-3015 PCIs/y) quartile of institutional volume was 0.75 (95% CI, 0.51-1.10; P=0.14), 0.87 (95% CI, 0.57-1.34; P=0.54), and 0.51 (95% CI, 0.30-0.86; P=0.01), respectively. These findings were consistent in rates of in-hospital death or any complication. Conversely, operator PCI volume was not significantly associated with in-hospital outcomes. Conclusions Institutional rather than operator-based PCI volume was associated with better in-hospital outcomes in patients undergoing PCI for unprotected left main coronary artery disease.
  • Varun Sundaram, Kieran Rothnie, Chloe Bloom, Rosita Zakeri, Jayakumar Sahadevan, Ajay Singh, Toshiyuki Nagai, James Potts, Jadwiga Wedzicha, Liam Smeeth, Daniel Simon, Adam Timmis, Sanjay Rajagopalan, Jennifer Kathleen Quint
    Heart (British Cardiac Society) 106 (9) 677 - 685 2020/05 
    OBJECTIVES: To characterise peak cardiac troponin levels, in patients presenting with acute myocardial infarction (AMI), according to their comorbid condition and determine the influence of peak cardiac troponin (cTn) levels on mortality. METHODS: We included patients with the first admission for AMI in the UK. We used linear regression to estimate the association between eight common comorbidities (diabetes mellitus, previous angina, peripheral arterial disease, previous myocardial infarction (MI), chronic kidney disease (CKD), cerebrovascular disease, chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD)) and peak cTn. Peak cTn levels were adjusted for age, sex, smoking status and comorbidities. Logistic regression and restricted cubic spline models were employed to investigate the association between peak cTn and 180-day mortality for each comorbidity. RESULTS: 330 367 patients with ST elevation myocardial infarction and non-ST elevation myocardial infarction were identified. Adjusted peak cTn levels were significantly higher in patients with CKD (adjusted % difference in peak cTnT for CKD=42%, 95% CI 13.1 to 78.4) and significantly lower for patients with COPD, previous angina, previous MI and CHF when compared with patients without the respective comorbidities (reference group) (cTnI; COPD=-21.7%, 95% CI -29.1 to -13.4; previous angina=-24.2%, 95% CI -29.6 to -8.3; previous MI=-13.5%, 95% CI -20.6 to -5.9; CHF=-28%, 95% CI -37.2 to -17.6). Risk of 180-day mortality in most of the comorbidities did not change substantially after adjusting for peak cTn. In general, cTnI had a stronger association with mortality than cTnT. CONCLUSIONS: In this nationwide analysis of patients presenting with AMI, comorbidities substantially influenced systemic concentrations of peak cTn. Comorbid illness is a significant predictor of mortality regardless of peak cTn levels and should be taken into consideration while interpreting cTn both as a diagnostic and prognostic biomarker.
  • Naotsugu Iwakami, Toshiyuki Nagai, Toshiaki A Furukawa, Aran Tajika, Akira Onishi, Kunihiro Nishimura, Soshiro Ogata, Michikazu Nakai, Misa Takegami, Hiroki Nakano, Yohei Kawasaki, Ana Carolina Alba, Gordon Henry Guyatt, Yasuyuki Shiraishi, Shun Kohsaka, Takashi Kohno, Ayumi Goda, Atsushi Mizuno, Tsutomu Yoshikawa, Toshihisa Anzai
    Journal of clinical epidemiology 121 71 - 80 2020/05 [Refereed][Not invited]
     
    OBJECTIVES: The objective of the study was to identify determinants of external validity of prognostic models. STUDY DESIGN AND SETTING: We systematically searched for studies reporting prognostic models of heart failure (HF) and examined their performance for predicting 30-day death in a cohort of consecutive 3,452 acute HF patients. We applied published critical appraisal tools and examined whether bias or other characteristics of original derivation studies determined model performance. RESULTS: We identified 224 models from 6,354 eligible studies. The mean c-statistic in the cohort was 0.64 (standard deviation, 0.07). In univariable analyses, only optimal sampling assessed by an adequate and valid description of the sampling frame and recruitment details to collect the population of interest (total score range: 0-2, higher scores indicating lower risk of bias) was associated with high performance (standardized β = 0.25, 95% CI: 0.12 to 0.38, P < 0.001). It was still significant after adjustment for relevant study characteristics, such as data source, scale of study, stage of illness, and study year (standardized β = 0.24, 95% CI: 0.07 to 0.40, P = 0.01). CONCLUSION: Optimal sampling representing the gap between the population of interest and the studied population in derivation studies was a key determinant of external validity of HF prognostic models.
  • Hayato Hosoda, Yasuhide Asaumi, Teruo Noguchi, Yoshiaki Morita, Yu Kataoka, Fumiyuki Otsuka, Kazuhiro Nakao, Masashi Fujino, Toshiyuki Nagai, Michikazu Nakai, Kunihiro Nishimura, Atsushi Kono, Yoshiaki Komori, Tomoya Hoshi, Akira Sato, Tomohiro Kawasaki, Chisato Izumi, Kengo Kusano, Tetsuya Fukuda, Satoshi Yasuda
    Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance 22 (1) 27 - 27 2020/04/27 [Refereed][Not invited]
     
    In the original publication of this article [1] the wording of '3Di-PMR' was different between the text and figures.
  • Yuta Kobayashi, Kazunori Omote, Toshiyuki Nagai, Kiwamu Kamiya, Takao Konishi, Takuma Sato, Yoshiya Kato, Hirokazu Komoriyama, Shingo Tsujinaga, Hiroyuki Iwano, Kazuhiro Yamamoto, Tsutomu Yoshikawa, Yoshihiko Saito, Toshihisa Anzai
    The American journal of cardiology 125 (5) 772 - 776 2020/03/01 [Refereed][Not invited]
     
    Elevated serum uric acid (UA) is associated with an increased risk of cardiovascular disease and worse clinical outcome in patients with cardiovascular disease. Nevertheless, the prognostic value of serum UA level in hospitalized heart failure patients with preserved ejection fraction (HFpEF) has not been fully elucidated. The aim of this study was to investigate whether serum UA level on admission could be associated with subsequent mortality in hospitalized patients with HFpEF. We examined 516 consecutive hospitalized HFpEF (left ventricular ejection fraction ≥50%) patients with decompensated heart failure from our HFpEF-specific multicenter registry who had serum UA data on admission. The primary outcome of interest was all-cause death. During a median follow-up period of 749 (interquartile range 540 to 831) days, 90 (17%) patients died. Higher serum UA level was significantly related to increased incidence of all-cause death (p = 0.016). In addition, patients with higher serum UA (≥6.6 mg/dl, median) and plasma B-type natriuretic peptide (≥401.2 pg/ml, median) levels had the highest incidence of all-cause death in the groups (p = 0.002). In multivariable Cox regression analysis, serum UA was an independent determinant of mortality (hazards ratio 1.23, 95% confidence interval 1.10 to 1.39) even after adjustment for prespecified confounders, renal function and the use of diuretics before admission. In conclusions, higher admission serum UA was an independent determinant of mortality in hospitalized HFpEF patients. Our findings indicate the importance of assessing admission serum UA level for further risk stratification in hospitalized patients with HFpEF.
  • Kazunori Omote, Takuma Sato, Toshiyuki Nagai, Toshihisa Anzai
    Heart and vessels 35 (3) 442 - 442 0910-8327 2020/03 [Refereed][Not invited]
  • Taro Temma, Toshiyuki Nagai, Masaya Watanabe, Rui Kamada, Yumi Takahashi, Hikaru Hagiwara, Taro Koya, Motoki Nakao, Kazunori Omote, Kiwamu Kamiya, Hiroyuki Iwano, Kazuhiro Yamamoto, Tsutomu Yoshikawa, Yoshihiko Saito, Toshihisa Anzai
    Circulation journal : official journal of the Japanese Circulation Society 84 (3) 397 - 403 2020/02/25 [Refereed][Not invited]
     
    BACKGROUND: Atrial fibrillation (AF) is an important prognostic determinant in heart failure (HF) with preserved ejection fraction (HFpEF). However, it is unclear which HFpEF phenotypes are affected by AF in terms of long-term clinical outcomes because HFpEF is a heterogeneous syndrome with comorbidities such as coronary artery disease (CAD). In this study we determined the differential prognostic significance of AF in HFpEF patients according to CAD status.Methods and Results:Data for 408 hospitalized HFpEF patients enrolled in the Japanese Heart Failure Syndrome with Preserved Ejection Fraction Nationwide Multicenter Registry were analyzed. Patients were divided into 4 groups according to the presence of AF and CAD. The primary outcome was the composite of all-cause death and HF rehospitalization. The incidence of adverse events was higher in the AF-non-CAD than non-AF-non-CAD group (P=0.004). On multivariable Cox regression analysis with prespecified confounders, AF-non-CAD was significantly associated with an increased risk of adverse events than non-AF-non-CAD (adjusted HR, 1.91; 95% CI: 1.02-3.92) regardless of the type of AF. In contrast, risk was comparable between the AF-CAD and non-AF-CAD groups (adjusted HR, 1.24; 95% CI: 0.64-2.47). CONCLUSIONS: In HFpEF patients without CAD, AF was independently related to adverse events, indicating that intensive management of AF would have more beneficial effects particularly in HFpEF patients without CAD.
  • Tetsuo Yamaguchi, Michikazu Nakai, Yoko Sumita, Kunihiro Nishimura, Toshiyuki Nagai, Toshihisa Anzai, Yasushi Sakata, Hitoshi Ogino
    European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery 59 (2) 219 - 225 1078-5884 2020/02 [Refereed][Not invited]
     
    OBJECTIVE: This study aimed to clarify the impact of endovascular aneurysm repair (EVAR) on clinical outcomes in Japanese patients of advanced age with ruptured abdominal aortic aneurysm (rAAA). METHODS: This was a national registry based retrospective comparative study, using data from the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC), a nationwide claim based database from more than 600 hospitals. Patients admitted with rAAA between April 1, 2012, and March 31, 2015 were included in the study. Patient characteristics, management, and outcomes were compared between the elderly (aged ≥ 80 y) and the less old. The primary endpoint was in hospital mortality; the secondary endpoint was the functional status at discharge. RESULTS: Of 3 969 eligible patients, 49.9% were categorised as elderly. Elderly patients had a higher prevalence of female gender (41.8% vs. 17.0%, p < .001) and disturbance of consciousness on admission (28.6% vs. 20.7%, p < .001). They were less likely to undergo open surgical repair (31.6% vs. 56.7%, p < .001), although EVAR was performed similarly in both groups (13.7% vs. 14.8%, p = .33). The unadjusted mortality rate (61.8% vs. 37.6%, p < .001) and mean Barthel index at discharge (73.0 vs. 91.8, p < .001) were statistically significantly worse in the elderly. Multilevel mixed effect logistic regression analyses showed that old age was detected as an independent predictor of in hospital death (odds ratio 2.75; 95% confidence interval, 2.39-3.17; p < .001). However, for patients who received EVAR, old age was not statistically significant (odds ratio 1.13; 95% confidence interval, 0.77-1.66; p = .53). CONCLUSION: Elderly patients with rAAA were less likely to be offered open surgical repair, and the mortality among those who received surgery was high. However, for the small subgroup of elderly patients currently selected for EVAR there was a favourable outcome. The further implementation of EVAR for rAAA in Japan, especially for elderly patients with suitable anatomy, may be justified.
  • Kazunori Omote, Toshiyuki Nagai, Hiroyuki Iwano, Shingo Tsujinaga, Kiwamu Kamiya, Tadao Aikawa, Takao Konishi, Takuma Sato, Yoshiya Kato, Hirokazu Komoriyama, Yuta Kobayashi, Kazuhiro Yamamoto, Tsutomu Yoshikawa, Yoshihiko Saito, Toshihisa Anzai
    ESC heart failure 7 (1) 167 - 175 2020/02 [Refereed][Not invited]
     
    AIMS: The prognostic implication of left ventricular outflow tract velocity time integral (LVOT-VTI) on admission in hospitalized heart failure with preserved ejection fraction (HFpEF) patients has not been determined. We sought to investigate whether LVOT-VTI on admission is associated with worse clinical outcomes in hospitalized patients with HFpEF. METHODS AND RESULTS: We studied consecutive 214 hospitalized HFpEF patients who had accessible LVOT-VTI data on admission, from a prospective HFpEF-specific multicentre registry. The primary outcome of interest was the composite of all-cause death and readmission due to heart failure. During a median follow-up period of 688 (interquartile range 162-810) days, the primary outcome occurred in 83 patients (39%). The optimal cut-off value of LVOT-VTI for the primary outcome estimated by receiver operating characteristic analysis was 15.8 cm. Lower LVOT-VTI was significantly associated with the primary outcome compared with higher LVOT-VTI (P = 0.005). Multivariable Cox regression analyses revealed that lower LVOT-VTI was an independent determinant of the primary outcome (hazard ratio 0.94, 95% confidence interval 0.91-0.98). In multivariable linear regression, haemoglobin level was the strongest independent determinant of LVOT-VTI among clinical parameters (β coefficient = -0.61, P = 0.007). Furthermore, patients with lower LVOT-VTI and anaemia had the worst clinical outcomes among the groups (P < 0.001). CONCLUSIONS: Lower admission LVOT-VTI was an independent determinant of worse clinical outcomes in hospitalized HFpEF patients, indicating that LVOT-VTI on admission might be useful for categorizing a low-flow HFpEF phenotype and risk stratification in hospitalized HFpEF patients.
  • Hayato Hosoda, Yasuhide Asaumi, Teruo Noguchi, Yoshiaki Morita, Yu Kataoka, Fumiyuki Otsuka, Kazuhiro Nakao, Masashi Fujino, Toshiyuki Nagai, Michikazu Nakai, Kunihiro Nishimura, Atsushi Kono, Yoshiaki Komori, Tomoya Hoshi, Akira Sato, Tomohiro Kawasaki, Chisato Izumi, Kengo Kusano, Tetsuya Fukuda, Satoshi Yasuda
    Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance 22 (1) 5 - 5 2020/01/16 [Refereed][Not invited]
     
    BACKGROUND: Periprocedural myocardial injury (pMI) is a common complication of elective percutaneous coronary intervention (PCI) that reduces some of the beneficial effects of coronary revascularization and impacts the risk of cardiovascular events. We developed a 3-dimensional volumetric cardiovascular magnetic resonance (CMR) method to evaluate coronary high intensity plaques and investigated their association with pMI after elective PCI. METHODS: Between October 2012 and October 2016, 141 patients with stable coronary artery disease underwent T1-weighted CMR imaging before PCI. A conventional 2-dimensional CMR plaque-to-myocardial signal intensity ratio (2D-PMR) and the newly developed 3-dimensional integral of PMR (3Di-PMR) were measured. 3Di-PMR was determined as the sum of PMRs above a threshold of > 1.0 for voxels in a target plaque. pMI was defined as high-sensitivity cardiac troponin T > 0.07 ng/mL. RESULTS: pMI following PCI was observed in 46 patients (33%). 3Di-PMR was significantly higher in patients with pMI than those without pMI. The optimal 3Di-PMR cutoff value for predicting pMI was 51 PMR*mm3 and the area under the receiver operating characteristic curve (0.753) was significantly greater than that for 2D-PMR (0.683, P = 0.015). 3Di-PMR was positively correlated with lipid volume (r = 0.449, P < 0.001) based on intravascular ultrasound. Stepwise multivariable analysis showed that 3Di-PMR ≥ 51 PMR*mm3 and the presence of a side branch at the PCI target lesion site were significant predictors of pMI (odds ratio [OR], 11.9; 95% confidence interval [CI], 4.6-30.4, P < 0.001; and OR, 4.14; 95% CI, 1.6-11.1, P = 0.005, respectively). CONCLUSIONS: 3Di-PMR coronary assessment facilitates risk stratification for pMI after elective PCI. TRIAL REGISTRATION: retrospectively registered.
  • Atsushi Tada, Takao Konishi, Takuma Sato, Tomoya Sato, Takuya Koizumi, Sakae Takenaka, Yoshifumi Mizuguchi, Takahide Kadosaka, Ko Motoi, Yuta Kobayashi, Hirokazu Komoriyama, Yoshiya Kato, Kazunori Omote, Shingo Tsujinaga, Rui Kamada, Kiwamu Kamiya, Hiroyuki Iwano, Toshiyuki Nagai, Nanase Okazaki, Yoshihiro Matsuno, Toshihisa Anzai
    Cardiology journal 27 (4) 443 - 444 2020
  • Takao Konishi, Naohiro Funayama, Tadashi Yamamoto, Daisuke Hotta, Yuta Kobayashi, Hirokazu Komoriyama, Yoshiya Kato, Kazunori Omote, Takuma Sato, Kiwamu Kamiya, Toshiyuki Nagai, Shinya Tanaka, Toshihisa Anzai
    Cardiology journal 27 (2) 204 - 205 2020 [Refereed][Not invited]
  • Hirokazu Komoriyama, Satonori Tsuneta, Noriko Oyama-Manabe, Kiwamu Kamiya, Toshiyuki Nagai
    European heart journal cardiovascular Imaging 21 (1) 21 - 21 2047-2404 2020/01/01 [Refereed][Not invited]
  • Naotsugu Iwakami, Toshiyuki Nagai, Toshiaki A Furukawa, Kunihiro Nishimura, Toshihisa Anzai
    Circulation reports 2 (1) 10 - 16 2019/12/05 
    Prediction models are combinations of predictors to assess the risks of specific endpoints such as the presence or prognosis of a disease. Many novel predictors have been developed, modelling techniques have been evolving, and prediction models are currently abundant in the medical literature, especially in cardiovascular medicine, but evidence is still lacking regarding how to use them. Recent methodological advances in systematic reviews and meta-analysis have enabled systematic evaluation of prediction model studies and quantitative analysis to identify determinants of model performance. Knowing what is critical to model performance, under what circumstances model performance remains adequate, and when a model might require further adjustment and improvement will facilitate effective utilization of prediction models and will enhance diagnostic and prognostic accuracy in clinical practice. In this review article, we provide a current methodological overview of the attempts to implement evidence-based utilization of prognostic prediction models for all potential model users, including patients and their families, health-care providers, administrators, researchers, guideline developers and policy makers.
  • Omote Kazunori, Nagai Toshiyuki, Kamiya Kiwamu, Aikawa Tadao, Tsujinaga Shingo, Kato Yoshiya, Komoriyama Hirokazu, Iwano Hiroyuki, Yamamoto Kazuhiro, Yoshikawa Tsutomu, Saito Yoshihiko, Anzai Toshihisa
    福田記念医療技術振興財団情報 (32) 41 - 54 2019/12 
    収縮機能維持心不全(HFpEF)多施設レジストリーにて、入院時に三尖弁逆流圧較差(TRPG)を測定した非代償性HFpEF患者(左室駆出分画≧50%)469名(女232名、平均78.3歳)を対象として、入院TRPGの予後的意義を検討した。主要評価項目は総死亡率とした。その結果、入院時TRPGは推定肺毛細血管楔入圧(PCWP)および左房径(LAD)と有意に相関した。追跡期間中央値の748日までに患者83名が死亡した。TRPG高値患者はTRPG低値患者に比べて有意に死亡率が高かった。多変量解析では、TRPG上昇が事前指定の交絡因子と腎機能による調整後の死亡率の独立決定因子であった。以上より、入院TRPG上昇はHFpEF入院患者の死亡率の独立決定因子であり、入院時のTRPGは有用なリスク分類の指標になると考えられた。
  • Kazunori Omote, Toshiyuki Nagai, Kiwamu Kamiya, Tadao Aikawa, Shingo Tsujinaga, Yoshiya Kato, Hirokazu Komoriyama, Hiroyuki Iwano, Kazuhiro Yamamoto, Tsutomu Yoshikawa, Yoshihiko Saito, Toshihisa Anzai
    Journal of cardiac failure 25 (12) 978 - 985 1071-9164 2019/12 [Refereed][Not invited]
     
    BACKGROUND: Doppler-estimated peak systolic tricuspid regurgitation pressure gradient (TRPG) is a representative noninvasive parameter for evaluating pulmonary artery systolic pressure, which can be a determinant of adverse outcomes in chronic heart failure with preserved ejection fraction (HFpEF). However, the prognostic implications of TRPG at admission for hospitalized patients with HFpEF are undetermined. METHODS AND RESULTS: We examined 469 consecutive hospitalized patients with decompensated HFpEF (left ventricular ejection fraction ≥ 50%) who underwent TRPG measurement at admission in our HFpEF multicenter registry. The primary outcome of interest was all-cause death. Admission TRPG was significantly correlated with estimated pulmonary capillary wedge pressure and left atrial dimension (r = 0.24, P < 0.001 and r = 0.21, P < 0.001, respectively). During a median follow-up period of 748 (IQR 540-820) days, 83 patients died. Higher TRPG was significantly associated with higher mortality compared to lower TRPG (log-rank; P = 0.007). Multivariable analysis revealed that elevated TRPG was an independent determinant of mortality (HR 1.02, 95% CI 1.01-1.04, P = 0.008) after adjustment for prespecified confounders and renal function. CONCLUSIONS: Elevated TRPG at admission was an independent determinant of mortality in hospitalized patients with HFpEF, indicating that TRPG at admission could be a useful marker for risk stratification in these patients.
  • Fumio Terasaki, Arata Azuma, Toshihisa Anzai, Nobukazu Ishizaka, Yoshio Ishida, Mitsuaki Isobe, Takayuki Inomata, Hatsue Ishibashi-Ueda, Yoshinobu Eishi, Masafumi Kitakaze, Kengo Kusano, Yasushi Sakata, Noriharu Shijubo, Akihito Tsuchida, Hiroyuki Tsutsui, Takatomo Nakajima, Satoshi Nakatani, Taiko Horii, Yoshikazu Yazaki, Etsuro Yamaguchi, Tetsuo Yamaguchi, Tomomi Ide, Hideo Okamura, Yasuchika Kato, Masahiko Goya, Mamoru Sakakibara, Kyoko Soejima, Toshiyuki Nagai, Hiroshi Nakamura, Takashi Noda, Takuya Hasegawa, Hideaki Morita, Tohru Ohe, Yasuki Kihara, Yoshihiko Saito, Yukihiko Sugiyama, Shin-Ichiro Morimoto, Akira Yamashina
    Circulation journal : official journal of the Japanese Circulation Society 83 (11) 2329 - 2388 1346-9843 2019/10/25 [Refereed][Not invited]
  • 永井 利幸, 相川 忠夫, 安斉 俊久
    日本サルコイドーシス/肉芽腫性疾患学会雑誌 日本サルコイドーシス 39 (1-2) 73 - 76 1883-1273 2019/10 [Refereed][Not invited]
     
    18F-fluorodeoxyglucose-positron emission tomography(FDG-PET)は,心臓サルコイドーシス(心サ症)の診断および病態評価に有用と考えられるが,FDG-PETにより評価された活動性炎症所見と臨床経過の乖離がしばしば経験される.今回我々はFDG-PET所見に増悪所見を認めた一方で臨床経過は改善を認めた症例,およびFDG-PET所見に改善所見を認めた一方で臨床経過は増悪を認めた症例を経験した.また,心サ症確診症例111例のうち,長期経過観察中にFDG-PET所見の増悪を認めた13例を検討した結果,同時に有害事象を伴う症例は6例であり,そのうち増悪時免疫抑制療法が中止されていた症例は3例であった.全例免疫抑制療法を強化したものの,その後2例に再度有害事象が発生した.一方,FDG-PET所見の増悪に有害事象を伴わない症例は7例であり,そのうち5例で免疫抑制療法を強化したものの,2例に再度有害事象が発生した.免疫抑制療法中のFDG-PET所見の変化が持つ臨床的意義には未だ不明な点が多く,今後の症例蓄積と前向き多施設研究が必要である.(著者抄録)
  • Yu Sato, Akiomi Yoshihisa, Masayoshi Oikawa, Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Kazuhiro Yamamoto, Yasuchika Takeishi, Toshihisa Anzai
    European heart journal. Acute cardiovascular care 8 (7) 623 - 633 2048-8726 2019/10 [Refereed][Not invited]
     
    INTRODUCTION: Hyponatremia predicts adverse prognosis in patients with heart failure in particular with reduced ejection fraction. In contrast, it has recently been reported that hyponatremia on admission is not a predictor of post-discharge mortality in patients with heart failure with preserved ejection fraction. We investigated the prognostic impact of hyponatremia at discharge in patients with heart failure with preserved ejection fraction and its clinical characteristics. METHODS AND RESULTS: The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese patients hospitalised with heart failure with preserved ejection fraction and left ventricular ejection fraction of 50% or greater. Five hundred consecutive patients were enrolled in this analysis. We divided the patients into two groups based on their sodium serum levels at discharge: hyponatremia group (sodium <135 mEq/L, n=50, 10.0%) and control group (sodium ⩾135 mEq/L, n=450, 90.0%). This present analysis had two primary endpoints: all-cause death and all-cause death or rehospitalisation for heart failure. At discharge, the hyponatremia group had lower systolic blood pressure (110.0 mmHg vs. 114.5 mmHg, P=0.014) and higher levels of urea nitrogen (31.9 mg/dL vs. 24.2 mg/dL, P=0.032). In the Kaplan-Meier analysis, more patients in the hyponatremia group reached the primary endpoints than those in the control group (log rank <0.01, respectively). In the Cox proportional hazard analysis, hyponatremia at discharge was a predictor of the two endpoints (all-cause death, hazard ratio 2.708, 95% confidence interval 1.557-4.708, P<0.001; all-cause death or rehospitalisation for heart failure, hazard ratio 1.829, 95% confidence interval 1.203-2.780, P=0.005). CONCLUSIONS: Hyponatremia at discharge is associated with adverse prognosis in hospitalised patients with heart failure with preserved ejection fraction.
  • Yu Sato, Akiomi Yoshihisa, Masayoshi Oikawa, Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Kazuhiro Yamamoto, Yasuchika Takeishi, Toshihisa Anzai
    International heart journal 60 (4) 876 - 885 1349-2365 2019/07/27 [Refereed][Not invited]
     
    The clinical scenario, which is based on systolic blood pressure (SBP) upon admission, is useful for classifying and determining initial treatment for acute heart failure (HF). However, the prognostic significance of SBP following the initial treatment is unclear.The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, and prospective registration of consecutive Japanese patients hospitalized with HF with preserved ejection fraction (HFpEF) and left ventricular ejection fraction ≥ 50%. We divided 525 patients into three groups based on their SBP on the day following hospitalization: high (SBP > 140 mmHg, n = 72, 13.7%); normal (100 ≤ SBP ≤ 140 mmHg, n = 379, 72.2%); and low (SBP < 100 mmHg, n = 74, 14.1%) groups. This analysis had two primary endpoints: (1) all-cause death and (2) all-cause death or rehospitalization for HF. In the Kaplan-Meier analysis, both of the endpoints were the highest in the low group (Log-Rank < 0.05, respectively). Compared to the normal and high groups, the low group demonstrated a higher prevalence of atrial fibrillation (67.1%, 63.9%, and 47.8%, P = 0.026) and the lowest left ventricular outflow tract velocity time integral determined by echocardiography (16.4 cm, 19.4 cm, and 23.3 cm, P = 0.001). In the multivariable Cox proportional hazard analysis, low SBP on the day following hospitalization was an independent predictor of all-cause death (hazard ratio 1.868, 95% confidence interval 1.024-3.407, P = 0.042) and the composite endpoint (hazard ratio 1.660, 95% confidence interval 1.103-2.500, P = 0.015).Classification based on SBP on the day following initial treatment predicts post-discharge prognosis in hospitalized patients with HFpEF.
  • Tadao Aikawa, Toshiyuki Nagai, Toshihisa Anzai
    International journal of cardiology 287 50 - 52 0167-5273 2019/07/15 [Refereed][Not invited]
  • Yasuyuki Shiraishi, Shun Kohsaka, Toshiyuki Nagai, Ayumi Goda, Atsushi Mizuno, Yuji Nagatomo, Yasumori Sujino, Ryoma Fukuoka, Mitsuaki Sawano, Takashi Kohno, Keiichi Fukuda, Toshihisa Anzai, Ramin Shadman, Todd Dardas, Wayne C Levy, Tsutomu Yoshikawa
    Journal of cardiac failure 25 (7) 561 - 567 1071-9164 2019/07 [Refereed][Not invited]
     
    BACKGROUND: Precise risk stratification in heart failure (HF) patients enables clinicians to tailor the intensity of their management. The Seattle Heart Failure Model (SHFM), which uses conventional clinical variables for its prediction, is widely used. We aimed to externally validate SHFM in Japanese HF patients with a recent episode of acute decompensation requiring hospital admission. METHODS AND RESULTS: SHFM was applied to 2470 HF patients registered in the West Tokyo Heart Failure and National Cerebral And Cardiovascular Center Acute Decompensated Heart Failure databases from 2006 to 2016. Discrimination and calibration were assessed with the use of the c-statistic and calibration plots, respectively, in HF patients with reduced ejection fraction (HFrEF; <40%) and preserved ejection fraction (HFpEF; ≥40%). In a perfectly calibrated model, the slope and intercept would be 1.0 and 0.0, respectively. The method of intercept recalibration was used to update the model. The registered patients (mean age 74 ± 13 y) were predominantly men (62%). Overall, 572 patients (23.2%) died during a mean follow-up of 2.1 years. Among HFrEF patients, SHFM showed good discrimination (c-statistic = 0.75) but miscalibration, tending to overestimate 1-year survival (slope = 0.78; intercept = -0.22). Among HFpEF patients, SHFM showed modest discrimination (c-statistic = 0.69) and calibration, tending to underestimate 1-year survival (slope = 1.18; intercept = 0.16). Intercept recalibration (replacing the baseline survival function) successfully updated the model for HFrEF (slope = 1.03; intercept = -0.04) but not for HFpEF patients. CONCLUSIONS: In Japanese acute HF patients, SHFM showed adequate performance after recalibration among HFrEF patients. Using prediction models to tailor the care for HF patients may improve the allocation of medical resources.
  • Keisuke Okuno, Yoshiro Naito, Masanori Asakura, Masataka Sugahara, Tomotaka Ando, Seiki Yasumura, Toshiyuki Nagai, Yoshihiko Saito, Tsutomu Yoshikawa, Tohru Masuyama, Toshihisa Anzai
    Heart and vessels 34 (7) 1168 - 1177 0910-8327 2019/07 [Refereed][Not invited]
     
    High prevalence of anemia in heart failure with preserved left ventricular ejection fraction (HFpEF) has been reported. However, little is known about the association of anemia and gender with prognosis in HFpEF patients. In addition, effective blood hemoglobin (Hb) level for prognosis in HFpEF patients remains largely unknown. In this study, we investigated the association between anemia, gender, and prognosis in 535 HFpEF patients enrolled in Japanese heart failure syndrome with preserved ejection fraction registry. Furthermore, we assessed effective blood Hb level to predict prognosis in HFpEF patients. According to the World Health Organization criteria, the prevalence rate of anemia on admission was about 70% in both male and female HFpEF patients. Kaplan-Meier analysis for all-cause mortality demonstrated that anemic patients had poor prognosis compared with non-anemic patients in both male and female HFpEF patients. Interestingly, multivariate analysis revealed that blood Hb level at discharge was an independent predictor of all-cause mortality in both male and female HFpEF patients. According to survival classification and regression tree analysis, blood Hb level at discharge of 9.4 g/dL for male and 12.3 g/dL for female was more accurate cutoff value to predict all-cause mortality in HFpEF patients. Anemia was implicated in poor prognosis in both male and female HFpEF patients. In particular, blood Hb level at discharge was an independent predictor of all-cause mortality in both male and female HFpEF patients. Effective cutoff value of blood Hb level at discharge to predict all-cause mortality was lower in male than in female HFpEF patients.
  • Kazunori Omote, Toshiyuki Nagai, Naoya Asakawa, Kiwamu Kamiya, Yusuke Tokuda, Tadao Aikawa, Arata Fukushima, Keiji Noguchi, Yoshiya Kato, Hirokazu Komoriyama, Mutsumi Nishida, Yusuke Kudo, Hiroyuki Iwano, Takashi Yokota, Toshihisa Anzai
    Heart and vessels 34 (6) 984 - 991 0910-8327 2019/06 [Refereed][Not invited]
     
    Liver stiffness (LS) has been reported to be a marker of liver congestion caused by elevated central venous pressure in heart failure (HF) patients. Recent studies demonstrated that LS could be non-invasively measured by virtual touch quantification (VTQ). However, its prognostic implication in patients with acute decompensated heart failure (ADHF) is unclear. This study sought to determine whether LS measured by VTQ could be a determinant of subsequent adverse events in ADHF patients. We prospectively recruited 70 ADHF patients who underwent LS measurement by VTQ on admission in our university hospital between June 2016 and April 2018. The primary outcome of interest was the composite of all-cause mortality and worsening HF. During a median follow-up period of 272 (interquartile range 122-578) days, there were 26 (37%) events, including 5 (7%) deaths and 21 (30%) cases of worsening HF. The c-index of LS for predicting the composite of adverse events was 0.77 (95% CI 0.66-0.88), and the optimal cut-off value of LS was 1.50 m/s. Adverse events were more frequently observed in patients with high LS (≥ 1.50 m/s) compared to those with low LS (< 1.50 m/s). Multivariable Cox regression analyzes revealed that higher LS was independently associated with increased subsequent risk of adverse events after adjustment for confounders. In conclusion, high admission LS was an independent determinant of worse clinical outcomes in patients with ADHF. This finding suggests that LS on admission is useful for risk stratification of patients with ADHF.
  • Yu Sato, Akiomi Yoshihisa, Masayoshi Oikawa, Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Kazuhiro Yamamoto, Yasuchika Takeishi, Toshihisa Anzai
    Journal of cardiology 73 (6) 459 - 465 0914-5087 2019/06 [Refereed][Not invited]
     
    BACKGROUND: The prognostic impact of chronic obstructive pulmonary disease (COPD) on heart failure (HF) with preserved ejection fraction (HFpEF) patients and its clinical characteristics have not yet been fully examined. METHODS: The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese hospitalized HFpEF patients with left ventricular ejection fraction (LVEF) of ≥50%. Among 535 patients enrolled in the registry, 10 lacking COPD data, and seven who died during the first hospitalization, were excluded. Finally, 518 patients were enrolled in this analysis. We divided these patients into two groups: the COPD group (n=40, 7.7%) and the non-COPD group (n=478, 92.3%). This analysis had two primary endpoints: (1) all-cause death and (2) all-cause death or rehospitalization for HF. RESULTS: The COPD group showed a higher prevalence of male sex (70.0% vs. 48.1%, p=0.008), history of prior hospitalization for HF (63.2% vs. 35.1%, p=0.001), smoking history (71.8% vs. 43.3%, p=0.001), and a higher usage of loop diuretics (70.0% vs. 50.0%, p=0.015). In the follow-up period after discharge (median 733 days), there were 82 all-cause deaths and 127 rehospitalizations for HF. In the Kaplan-Meier analysis, the COPD group showed higher all-cause death and reached the composite endpoint more often than in the non-COPD group (all-cause death, log-rank 0.035; all-cause death or rehospitalization for HF, log-rank 0.025). In the Cox proportional hazard analysis, COPD was a predictor of all-cause death (hazard ratio 1.957, 95% confidence interval 1.037-3.694, p=0.038) and the composite endpoint (hazard ratio 1.694, 95% confidence interval 1.064-2.697, p=0.026). CONCLUSIONS: COPD is associated with adverse prognosis in hospitalized patients with HFpEF.
  • Toshiyuki Nagai, Toshihisa Anzai
    Circulation journal : official journal of the Japanese Circulation Society 83 (6) 1202 - 1203 1346-9843 2019/05/24 [Refereed][Not invited]
  • Daigo Chinen, Toshiyuki Nagai, Kazunori Uemura, Yukio Aikawa, Tetsufumi Motokawa, Yasuhide Asaumi, Takeshi Ogo, Hideaki Kanzaki, Teruo Noguchi, Toshihisa Anzai, Wataru Shimizu, Hisao Ogawa, Masaru Sugimachi, Satoshi Yasuda
    The American journal of cardiology 123 (9) 1464 - 1469 0002-9149 2019/05/01 [Refereed][Not invited]
     
    Although several tissue-Doppler imaging (TDI) models for pulmonary capillary wedge pressure (PCWP) estimation have been reported, their reliability remains uncertain. Our previous theoretical and experimental analyses suggest that right atrial pressure (RAP) corrected by tissue-Doppler imaging tricuspid/mitral annular peak systolic velocities (ST/SM) (RAP × ST/SM) reliably predicts elevated PCWP. We sought to investigate its clinical usefulness for predicting elevated PCWP in heart failure (HF) patients. Ninety-eight patients admitted with HF who underwent right heart catheterization were prospectively studied. RAP and PCWP were measured by right heart catheterization. Simultaneously, ST/SM, early diastolic transmitral flow velocity to mitral annular velocity ratio (E/Ea), and diameter of inferior vena cava at inspiration (IVCDi), a noninvasive surrogate for RAP, were measured by echocardiography. RAP correlated with IVCDi (R2 = 0.57). A significantly stronger correlation was observed between IVCDi corrected by ST/SM (IVCDi × ST/SM) and PCWP than between E/Ea and PCWP (R2 = 0.47 vs 0.18). Receiver-operating characteristic analyses indicated that IVCDi × ST/SM >16 mm predicted PCWP >18 mm Hg with 90% sensitivity and 77% specificity, and the area under the curve was 0.86, which was significantly larger than that of E/Ea (area under the curve=0.72). In conclusions, IVCDi × ST/SM is a new useful noninvasive model to predict elevated PCWP in HF patients.
  • Toshiyuki Nagai, Naotsugu Iwakami, Michikazu Nakai, Kunihiro Nishimura, Yoko Sumita, Atsushi Mizuno, Hiroyuki Tsutsui, Hisao Ogawa, Toshihisa Anzai
    International journal of cardiology 280 104 - 109 0167-5273 2019/04/01 [Refereed][Not invited]
     
    BACKGROUNDS: Carperitide is a recombinantly produced intravenous formulation of human atrial natriuretic peptide. Despite of negative impacts of nesiritide on clinical outcomes for acute heart failure (AHF), carperitide has been used for around a half of Japanese AHF patients as a vasodilator based on limited evidences. We sought to determine the effect of carperitide compared to nitrates in the early care for AHF patients treated with vasodilators. METHODS AND RESULTS: We conducted a cohort study of patients admitted with AHF to 808 hospitals from April 2012 to March 2014. Patients were extracted from 1,422,703 hospitalizations according to ICD-10 heart failure codes. Patients who had sepsis or mechanical supports during hospitalization were excluded. Outcomes were in-hospital death, length of hospitalization and cost of hospitalization. Among 76,924 patients, 45,595 were in patients treated with either carperitide or nitrates during the first 2 days (carperitide; 33,386, nitrates; 12,209). After application of inverse probability of treatment weighting with variables including demographics, comorbidities and treatments, there was perfect balance in both groups. Patients who were treated with carperitide had substantially higher covariate adjusted in-hospital mortality (HR 1.49 95%CI 1.35-1.64), longer length of hospitalization (Coefficients 0.062 95%CI 0.048 to 0.076) and greater cost of hospitalization (Coefficients 0.024 95%CI 0.010 to 0.037) compared to those treated with nitrates. CONCLUSIONS: In Japanese AHF patients during their early inpatient care, carperitide use was significantly associated with worse outcomes when compared to nitrates use, suggesting the routine use of carperitide might not be recommended as a first-line vasodilator for AHF.
  • 心不全患者におけるMRエラストグラフィで評価した肝硬度の増加は右心房圧の上昇を予測する(Increased Liver Stiffness Assessed by Magnetic Resonance Elastography Predicts Elevated Right Atrial Pressure in Patients with Heart Failure)
    加藤 喜哉, 永井 利幸, 小森山 弘和, 表 和徳, 相川 忠夫, 神谷 究, 常田 慧徳, 真鍋 徳子[大山], 安斉 俊久
    日本循環器学会学術集会抄録集 83回 PJ096 - 6 2019/03 [Refereed][Not invited]
  • 佐藤 悠, 義久 精臣, 及川 雅啓, 永井 利幸, 吉川 勉, 斎藤 能彦, 山本 一博, 竹石 恭知, 安斉 俊久
    日本循環器学会学術集会抄録集 83回 (8) PJ073 - 3 1071-9164 2019/03 [Refereed][Not invited]
     
    BACKGROUND: The characteristics and prognostic impact of persistent worsening renal function (WRF; defined as an increase in serum creatinine of >0.3 mg/dL during hospitalization) on heart failure with preserved ejection fraction have not yet been fully examined. METHODS AND RESULTS: This was a post hoc analysis of the Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry. We divided 523 patients with heart failure with preserved ejection fraction: the WRF group (n = 92 [17.6%]) and the non-WRF group (n = 431 [82.4%]). The WRF group showed a higher systolic blood pressure on admission and a higher prevalence of atherosclerotic diseases, respectively. Logistic regression analysis revealed that systolic blood pressure and loop diuretics were associated with WRF development (P < .05). The Kaplan-Meier analysis (median, 732 days) showed a higher all-cause death in the WRF group, as well as a higher composite end point of all-cause death or rehospitalization for HF (log-rank P < .001). The Cox proportional hazard analysis revealed WRF to be a predictor of both all-cause death (hazard ratio, 2.725; 95% confidence interval, 1.709-4.344; P < .001) and the composite end point (hazard ratio, 2.083; 95% confidence interval, 1.488-2.914; P < .001). CONCLUSIONS: Persistent WRF was associated with systolic blood pressure, atherosclerotic diseases, diuretics, and poor postdischarge prognosis in patients with heart failure with preserved ejection fraction.
  • 大江 由紀子, 植田 初江, 松山 高明, 永井 利幸, 池田 善彦, 大郷 恵子, 野口 暉夫, 安斉 俊久
    日本循環器学会学術集会抄録集 83回 (2) PJ073 - 6 2019/03 [Refereed][Not invited]
     
    Background The diagnosis of cardiac sarcoidosis ( CS ) is challenging because endomyocardial biopsy has only a 20% to 30% sensitivity rate for diagnosis and it presents with similar clinical features of idiopathic dilated cardiomyopathy ( DCM ). Lymphatic vessel proliferation in pulmonary sarcoidosis has been previously demonstrated. In this study, we compared endomyocardial biopsy samples obtained from patients with CS and DCM to determine whether lymph vessel counts using D2-40 immunostaining can be utilized as a complementary tool to distinguish CS from DCM . Methods and Results Endomyocardial biopsy tissues were obtained from 62 patients with CS (30 patients with a diagnosis made histologically, 32 patients with a diagnosis made clinically), and hematoxylin/eosin, Masson trichrome, and D2-40 immunostaining were performed. Their results were compared with those from 53 patients with DCM. The histological CS group showed significantly increased lymphatic vessels (12.0 [4.0-40.0] versus 2.6 [1.9-3.4], P<0.0001) and more severe mosaic fibrosis ( P<0.0001) compared with the DCM group. The optimal threshold was 7.5 lymphatic vessels, and this resulted in a sensitivity of 0.67 and specificity of 0.96. The clinical CS group diagnosed according to Japanese Circulation Society 2016 criteria showed increased lymphatic vessels (4.0 [3.3-9.0] versus 2.6 [1.9-3.4], P<0.0001), more severe mosaic fibrosis ( P<0.0001), more inflammatory cell infiltration (53% versus 0%, P<0.0001), and fatty infiltration within fibroblasts (50% versus 17%, P=0.0012) compared with the DCM group. The optimal threshold of lymphatic vessels was 3.5, which resulted in a sensitivity of 0.75 and specificity of 0.68. Conclusions Lymphatic vessel counts using D2-40 immunostaining may help to distinguish clinical CS without granuloma from DCM .
  • Hiroki Nakano, Kazunori Omote, Toshiyuki Nagai, Michikazu Nakai, Kunihiro Nishimura, Yasuyuki Honda, Satoshi Honda, Naotsugu Iwakami, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Satoshi Yasuda, Hisao Ogawa, Taishiro Chikamori, Toshihisa Anzai
    Circulation journal : official journal of the Japanese Circulation Society 83 (3) 614 - 621 1346-9843 2019/02/25 [Refereed][Not invited]
     
    BACKGROUND: The ideal mortality prediction model (MPM) for acute heart failure (AHF) patients would have sufficient and stable predictive ability for long-term as well as short-term mortality. However, published MPMs for AHF predominantly predict short-term mortality up to 90 days, and their prognostic performance for long-term mortality remains unclear. Methods and Results: We analyzed 609 AHF patients in a prospective registry from January 2013 to May 2016. We compared the prognostic performance for long-term mortality among 8 systematically identified MPMs for AHF that predict short-term mortality up to 90 days from admission. The PROTECT 7-day model showed the highest c-index for long-term as well as short-term mortality among the studied MPMs. Sensitivity analyses revealed serum albumin and total cholesterol to be the most important variables, as dropping these variables resulted in a significant decline in c-index, when compared with other variables specific to the PROTECT 7-day model. Furthermore, significant improvements in c-index and net reclassification were observed when serum albumin or serum albumin plus total cholesterol was added to the studied MPMs, other than the PROTECT 7-day model. CONCLUSIONS: The PROTECT 7-day model demonstrated the highest predictive performance for long-term as well as short-term mortality in AHF patients among the published MPMs. Our findings indicate the importance of accounting for nutritional status such as serum albumin and total cholesterol in AHF patients when developing a MPM.
  • Kyohei Marume, Seiji Takashio, Toshiyuki Nagai, Kenichi Tsujita, Yoshihiko Saito, Tsutomu Yoshikawa, Toshihisa Anzai
    Circulation journal : official journal of the Japanese Circulation Society 83 (2) 357 - 367 1346-9843 2019/01/25 [Refereed][Not invited]
     
    BACKGROUND: Statins might be associated with improved survival in patients with heart failure with preserved ejection fraction (HFpEF). The effect of statins in HFpEF without coronary artery disease (CAD), however, remains unclear. Methods and Results: From the JASPER registry, a multicenter, observational, prospective cohort with Japanese patients aged ≥20 years requiring hospitalization with acute HF and LVEF ≥50%, 414 patients without CAD were selected for outcome analysis. Based on prescription of statins at admission, we divided patients into the statin group (n=81) or no statin group (n=333). We followed them for 25 months. The association between statin use and primary (all-cause mortality) and secondary (non-cardiac death, cardiac death, or rehospitalization for HF) endpoints was assessed in the entire cohort and in a propensity score-matched cohort. In the propensity score-matched cohort, 3-year mortality was lower in the statin group (HR, 0.21; 95% CI: 0.06-0.72; P=0.014). The statin group had a significantly lower incidence of non-cardiac death (P=0.028) and rehospitalization for HF (P<0.001), but not cardiac death (P=0.593). The beneficial effect of statins on mortality did not have any significant interaction with cholesterol level or HF severity. CONCLUSIONS: Statin use has a beneficial effect on mortality in HFpEF without CAD. The present findings should be tested in an adequately powered randomized clinical trial.
  • Kazunori Omote, Masanao Naya, Kazuhiro Koyanagawa, Tadao Aikawa, Osamu Manabe, Toshiyuki Nagai, Kiwamu Kamiya, Yoshiya Kato, Hirokazu Komoriyama, Masato Kuzume, Nagara Tamaki, Toshihisa Anzai
    Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology 27 (6) 2135 - 2143 1071-3581 2019/01/04 [Refereed][Not invited]
     
    BACKGROUND: The aim of this study was to determine whether right ventricle (RV) 18F-fluorodeoxyglucose (FDG) uptake can predict positive findings of endomyocardial biopsy (EMB) in patients with cardiac sarcoidosis (CS). METHODS: 70 consecutive patients with clinically diagnosed CS who had undergone FDG PET were registered in the present study. Patients without EMB (n = 42) were excluded. Ultimately, 28 patients were studied. EMB samples were obtained from the RV septum. We evaluated the FDG uptake on six segments (RV, left ventricle anterior, septal, lateral, inferior, and apex). RESULTS: Positive EMB was found in six patients (21%). Patients were divided into two groups according to positive (n = 12 [43%]) or negative (n = 16 [57%]) RV FDG uptake. Patients with positive RV FDG uptake had a significantly higher frequency of positive EMB than those without (42% vs. 6%, P = 0.024). On the other hand, there was no EMB-predictive value for the FDG uptakes in the other five segments, the cardiac metabolic volume, total lesion glycolysis, left ventricular ejection fraction, or any electrocardiogram findings. CONCLUSIONS: FDG uptake of the RV but no other heart segment was associated with positive EMB in CS patients. The presence of RV FDG uptake could improve the rate of positive EMB up to 42% in patients with CS.
  • Yoshiya Kato, Arata Fukushima, Hiroyuki Iwano, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
    Journal of cardiology cases 18 (5) 175 - 179 2018/11 [Refereed][Not invited]
     
    Severe tricuspid regurgitation (TR) is reported to represent a hemodynamic pattern similar to that of constrictive pericarditis (CP), which should be clearly differentiated for appropriate management. We report the case of a patient with severe TR due to atrial fibrillation (AF) in whom hemodynamic monitoring played a role in the selection of the management strategy. An 81-year-old Japanese man with chronic AF was admitted due to worsening heart failure. Echocardiography showed the dilation of bilateral atria and a right ventricle with severe TR. The right heart catheterization demonstrated the elevation and equalization of diastolic pressures of four cardiac chambers with impaired diastolic filling pattern, which are hallmarks of pericardial constriction due to CP. Of note, the CP-like hemodynamics were completely normalized by 10 days of medical therapies including diuretics and carperitide. After his discharge and over a 1-year follow-up, he has never experienced worsening heart failure and remained NYHA class II with moderate TR. Medical management targeted at volume reduction and vasodilation can be a therapeutic option for CP-like hemodynamics in isolated severe TR related to AF. Repeated hemodynamic assessment is an appropriate tool to help our understanding of the CP-like physiology caused by severe TR based on chronic AF. .
  • Ozawa T, Kawakami S, Matsumoto M, Ishibashi-Ueda H, Nagai T, Noguchi T, Yasuda S
    Circulation journal : official journal of the Japanese Circulation Society 83 (6) 1415 - 1415 1346-9843 2018/10 [Refereed][Not invited]
  • Mitsuaki Sawano, Yasuyuki Shiraishi, Shun Kohsaka, Toshiyuki Nagai, Ayumi Goda, Atsushi Mizuno, Yasumori Sujino, Yuji Nagatomo, Takashi Kohno, Toshihisa Anzai, Keiichi Fukuda, Tsutomu Yoshikawa
    ESC heart failure 5 (4) 610 - 619 2018/08 [Refereed][Not invited]
     
    AIMS: Predictive models for heart failure patients are widely used in the clinical practice to stratify patients' mortality and enable clinicians to tailor and intensify their approach. However, such models have not been validated internationally. In addition, biomarkers are now frequently measured to obtain prognostic information, and the implications of this practice are not known. In this study, we aimed to validate the model performance of the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) score in a Japanese acute heart failure registry and further explore the incremental prognostic value of discharge B-type natriuretic peptide (BNP) level. METHODS AND RESULTS: In this study, we evaluated the registered data of 2215 consecutive acute HF patients (with 694 119 person-years follow-up) from a prospective multicentre registry (the West Tokyo Heart Failure) conducted in Japan from April 2006 to August 2016. The mean age was 73.0 ± 13.0, and 61.2% were male. The MAGGIC score demonstrated modest discrimination (c-index = 0.71, 95% confidence interval 0.67-0.74) and good calibration (R2 value = 0.97); there was constant overestimation for 1 year mortality. However, when the BNP level was added to the original MAGGIC variables, the model demonstrated good discrimination (c-index = 0.74, 95% confidence interval 0.70-0.78) with adequate calibration (R2 value = 0.91). The modified MAGGIC BNP score was externally validated in a separate Japanese registry (NaDEF) and demonstrated moderate discrimination (c-index = 0.69, 95% confidence interval 0.65-0.73) and calibration (R2 value = 0.85). CONCLUSION: The original MAGGIC score performed modestly in Japanese patients, but the addition of discharge BNP level enhanced model performance. The addition of objective biomarkers may result in effective modification of preexisting internationally recognized risk models and aid in multinational comparisons of heart failure patients' outcomes.
  • Manabu Matsumoto, Yasuhide Asaumi, Yuichi Nakamura, Takeshi Nakatani, Toshiyuki Nagai, Tomoaki Kanaya, Shoji Kawakami, Satoshi Honda, Yu Kataoka, Seiko Nakajima, Osamu Seguchi, Masanobu Yanase, Kunihiro Nishimura, Yoshihiro Miyamoto, Kengo Kusano, Toshihisa Anzai, Teruo Noguchi, Tomoyuki Fujita, Junjiro Kobayashi, Hatsue Ishibashi-Ueda, Hiroaki Shimokawa, Satoshi Yasuda
    ESC heart failure 5 (4) 675 - 684 2018/08 [Refereed][Not invited]
     
    AIMS: Patients with fulminant myocarditis (FM) often present with cardiogenic shock and require mechanical circulatory support, including extracorporeal membrane oxygenation (ECMO) and ventricular assist device (VAD) implantation. This study sought to clarify the determinants of successful weaning from ECMO in FM patients. METHODS AND RESULTS: We studied 37 consecutive FM patients supported by ECMO as the initial form of mechanical circulatory support between January 1995 and December 2014 in our hospital. Twenty-two (59%) patients were successfully weaned from ECMO, while 15 (41%) were not. There were significant differences in levels of peak creatine kinase and those of its MB isoform (CK-MB), left ventricular posterior wall thickness (LVPWT), and prevalence of cardiac rhythm disturbances. Receiver operating characteristic curve analysis revealed that a peak CK-MB level of 185 IU/L and LVPWT of 11 mm were the optimal cut-off values for predicting successful weaning from ECMO (areas under the curve, 0.89 and 0.85, respectively). During the follow-up [median 48 (interquartile range 8-147) months], 83% of FM patients who were weaned from ECMO survived, with preserved fractional shortening based on echocardiography. Of the 15 FM patients who were not weaned from ECMO, nine bridged to VAD, and only two were successfully weaned from VAD and survived. CONCLUSIONS: These results indicate that myocardial injury, as evidenced by CK-MB and LVPWT, and prolonged presence of cardiac rhythm disturbances are important clinical determinants of successful weaning from ECMO.
  • Toshiyuki Nagai, Varun Sundaram, Ahmad Shoaib, Yasuyuki Shiraishi, Shun Kohsaka, Kieran J Rothnie, Susan Piper, Theresa A McDonagh, Suzanna M C Hardman, Ayumi Goda, Atsushi Mizuno, Mitsuaki Sawano, Alan S Rigby, Jennifer K Quint, Tsutomu Yoshikawa, Andrew L Clark, Toshihisa Anzai, John G F Cleland
    European journal of heart failure 20 (8) 1179 - 1190 1388-9842 2018/08 [Refereed][Not invited]
     
    AIMS: Prognostic models for hospitalized heart failure (HHF) were developed predominantly for patients of European origin in the United States of America; it is unclear whether they perform similarly in other health care systems or for different ethnicities. We sought to validate published prediction models for HHF in the United Kingdom (UK) and Japan. METHODS AND RESULTS: Patients in the UK (n =894) and Japan (n =3158) were prospectively enrolled and were similar in terms of sex (∼60% men) and median age (∼77 years). Models predicted that British patients would have a higher mortality than Japanese, which was indeed true both for in-hospital (4.8% vs. 2.5%) and 180-day (20.7% vs. 9.5%) mortality. The model c-statistics for the published/derivation (range 0.70-0.76) and Japanese (range 0.75-0.77) cohorts were similar and higher than for the UK (0.62-0.75) but models consistently overestimated mortality in Japan. For in-hospital mortality, the OPTIMIZE-HF model performed best, providing similar discrimination in published/derivation, UK and Japanese cohorts [c-indices: 0.75 (0.74-0.77); 0.75 (0.68-0.81); and 0.77 (0.70-0.83), respectively], and least overestimated mortality in Japan. For 180-day mortality, the c-statistics for the ASCEND-HF model were similar in published/derivation (0.70) and UK [0.69 (0.64-0.74)] cohorts but higher in Japan [0.75 (0.71-0.79)]; calibration was good in the UK but again overestimated mortality in Japan. CONCLUSION: Calibration of published prediction models appears moderately accurate and unbiased when applied to British patients but consistently overestimates mortality in Japan. Identifying the reason why patients in Japan have a better than predicted prognosis is of great interest.
  • Yasuhiro Hamatani, Toshiyuki Nagai, Michikazu Nakai, Kunihiro Nishimura, Yasuyuki Honda, Hiroki Nakano, Satoshi Honda, Naotsugu Iwakami, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Kazunori Toyoda, Satoshi Yasuda, Hiroyuki Yokoyama, Hisao Ogawa, Toshihisa Anzai
    Stroke 49 (7) 1737 - 1740 0039-2499 2018/07 [Refereed][Not invited]
     
    BACKGROUND AND PURPOSE: The incidence of heart failure increases the subsequent risk of ischemic stroke, and its risk could be higher in the short-term period after an acute heart failure (AHF) event. However, its determinants remain to be clarified. Plasma D-dimer level reflects fibrin turnover and exhibits unique properties as a biomarker of thrombosis. The aim of this study is to investigate whether D-dimer level is a determinant of short-term incidence of ischemic stroke in patients with AHF. METHODS: We examined 721 consecutive hospitalized AHF patients with plasma D-dimer level on admission from our prospective registry between January 2013 and May 2016. The study end points were incidence of ischemic stroke during hospitalization and at 30 days after admission. RESULTS: Of the total participants (mean age, 76 years; male, 60%; atrial fibrillation, 54%; mean left ventricular ejection fraction, 38%), in-hospital ischemic stroke occurred in 18 patients (2.5%) during a median hospitalization period of 21 days, and 30-day ischemic stroke occurred in 16 patients (2.2%). Higher D-dimer level on admission was an independent determinant of subsequent risk of in-hospital ischemic stroke even after adjustment by CHA2DS2-VASc score (odds ratio, 2.29; 95% confidence interval, 1.46-3.60; P<0.001) or major confounders, including age, atrial fibrillation, and antithrombotic therapy (odds ratio, 2.31; 95% confidence interval, 1.43-3.74; P<0.001). Subgroup analyses showed consistent findings in patients without atrial fibrillation (odds ratio, 2.46; 95% confidence interval, 1.39-4.54; P=0.002) and those without antithrombotic therapy (odds ratio, 2.79; 95% confidence interval, 1.53-5.57; P<0.001). Similar results were obtained for 30-day ischemic stroke as an alternative outcome. CONCLUSIONS: Elevated plasma D-dimer level on admission was significantly associated with increased incidence of ischemic stroke shortly after admission for AHF, suggesting a predictive role of D-dimer for short-term ischemic stroke events in patients with AHF. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000017024.
  • Hiroki Nakano, Toshiyuki Nagai, Varun Sundaram, Michikazu Nakai, Kunihiro Nishimura, Yasuyuki Honda, Satoshi Honda, Naotsugu Iwakami, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Hisao Ogawa, Satoshi Yasuda, Taishiro Chikamori, Toshihisa Anzai, NaDEF investigators
    International Journal of Cardiology 261 114 - 118 1874-1754 2018/06/15 [Refereed][Not invited]
     
    Background: Iron deficiency (ID) is commonly observed in chronic heart failure (HF) patients and is associated with worse clinical outcomes. While ID is frequent finding in hospitalized heart failure (HHF), its impact on long-term outcome in HHF patients remains unclear. Methods: We evaluated iron status at discharge in 578 HHF patients. Absolute ID was defined as serum ferritin < 100 μg/L, and functional ID (FID) was defined as serum ferritin of 100–299 μg/L with transferrin saturation < 20%. The primary outcome of interest was the composite of all-cause mortality and HF admission at one year. Results: Among the study population, 185 had absolute ID, 88 had FID and 305 had no evidence of ID. At one-year post-discharge, 64 patients had died and 112 had been readmitted with HF. Patients with absolute ID had more adverse events than those with FID or no ID (p = 0.021). In multivariate Cox regression analyses, absolute ID was significantly associated with increased risk of adverse events at one year (HR 1.50, 95% CI 1.02–2.21, p = 0.040) compared with the remaining patients. Sensitivity analysis revealed that its prognostic effect did not differ across anemic status, or between HF with reduced and preserved ejection fraction (p for interaction = 0.17, 0.68, respectively). Conclusion: Absolute ID, but not FID, at discharge was associated with increased risk of one-year mortality or HF admission in patients with HHF. Further studies are required to evaluate the role of repleting iron stores and its impact on clinical outcomes in patients with HHF.
  • Yasuyuki Shiraishi, Toshiyuki Nagai, Shun Kohsaka, Ayumi Goda, Yuji Nagatomo, Atsushi Mizuno, Takashi Kohno, Alan Rigby, Keiichi Fukuda, Tsutomu Yoshikawa, Andrew L. Clark, John G. F. Cleland
    Clinical Research in Cardiology 107 (12) 1 - 8 1861-0692 2018/05/21 [Refereed][Not invited]
     
    Background: Mortality subsequent to a hospitalisation for heart failure is reported to be much lower in Japan than in the United Kingdom (UK). This could reflect differences in disease severity or in management. Accordingly, we directly compared patient backgrounds and outcomes between Japan and UK. Methods: Consecutive patients admitted to academic hospitals in the UK and Japan with heart failure had a common set of variables, including plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), collected during admission. Mortality during hospitalisations, at 90 and 180 days was recorded and stratified by quintile of NT-proBNP. Results: Overall, 935 patients were enrolled 197 from UK and 738 from Japan. Median (interquartile range) age [UK: 78 (71–88) vs. Japan: 78 (70–84) years p = 0.947], glomerular filtration rate [UK: 49 (34–68) vs. Japan: 49 (33–65) ml/min/1.73 m2 p = 0.209] and plasma NT-proBNP [UK: 4957 (2278–10,977) vs. Japan: 4155 (1972–9623) ng/l p = 0.186] were similar, but systolic blood pressure was lower in the UK [118 (105–131) vs. 137 (118–159) mmHg p < 0.001]. Patients with a higher plasma NT-proBNP had a worse prognosis in both countries in-hospital and post-discharge mortality rates were higher in the UK even after adjusting for prognostic variables including NT-proBNP. Conclusions: This analysis suggests that either unobserved differences in patient characteristics or differences in care (formal or informal) rather than greater heart failure severity may account for the worse outcome of heart failure in the UK compared to Japan.
  • Naotsugu Iwakami, Toshiyuki Nagai, Toshiaki A. Furukawa, Toshihisa Anzai
    International Journal of Cardiology 256 25 - 25 1874-1754 2018/04/01 [Refereed][Not invited]
  • Yasuhiro Hamatani, on behalf of the, Toshiyuki Nagai, Yasuyuki Shiraishi, Shun Kohsaka, Michikazu Nakai, Kunihiro Nishimura, Takashi Kohno, Yuji Nagatomo, Yasuhide Asaumi, Ayumi Goda, Atsushi Mizuno, Satoshi Yasuda, Hisao Ogawa, Tsutomu Yoshikawa, Toshihisa Anzai
    American Journal of Cardiology 121 (6) 731 - 738 1879-1913 2018/03/15 [Refereed][Not invited]
     
    Plasma B-type natriuretic peptide (BNP) is an important prognostic marker in patients with acute heart failure (AHF). However, it is unclear which BNP parameter, on admission, at discharge, or change during hospitalization, has the highest predictive performance for long-term adverse outcomes, and whether its prognostic impact differs according to the new European heart failure (HF) phenotype classification by left ventricular ejection fraction: heart failure with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). We examined 1,792 patients with AHF consisting of 860 (48%) HFrEFs, 318 (18%) HFmrEFs, and 614 (34%) HFpEFs. Prognostic performance of each BNP parameter was assessed by the Harrell c-index. During a median follow-up of 664 days, 344 (19%) patients died. Discharge BNP had the highest c-index (0.69) for mortality among all BNP parameters (p < 0.001). In multivariate Cox proportional hazard modeling, discharge BNP was associated with mortality in HFrEF, HFmrEF, and HFpEF patients with significant interaction (hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.57 to 2.41 HR 1.76, 95% CI 1.10 to 2.82 HR 1.46, 95% CI 1.12 to 1.91, respectively p = 0.011 for interaction). Moreover, the c-index of discharge BNP for mortality in HFrEF patients (0.72) was higher than that in HFmrEF patients (0.68) and HFpEF patients (0.65). Similar results were obtained for mortality or HF rehospitalization as alternative outcomes, except there was no statistically significant interaction among HF phenotypes. In conclusion, discharge BNP is a more reliable marker than other BNP parameters on long-term outcome prediction in patients with AHF, but its prognostic impact may be weakened in HFmrEF and HFpEF compared with HFrEF.
  • Satoshi Honda, on behalf of the, Toshiyuki Nagai, Kunihiro Nishimura, Michikazu Nakai, Yasuyuki Honda, Hiroki Nakano, Naotsugu Iwakami, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
    International Journal of Cardiology 254 189 - 194 1874-1754 2018/03/01 [Refereed][Not invited]
     
    Background Lower urinary sodium concentration (UNa) may reflect impaired renal perfusion, higher neurohormonal activity and diuretic resistance. However, the prognostic impact of UNa in patients with acute heart failure (AHF) has not been fully elucidated. Methods We investigate the association between UNa and clinical outcomes in 669 patients admitted with AHF in our prospective registry. Patients were stratified into tertiles based on UNa in a spot urine sample on admission. Results Patients with lower UNa were more likely to have a history of prior heart failure admission, β-blockers and diuretics use, and had lower blood pressure and serum sodium level, and higher blood urea nitrogen, estimated glomerular filtration rate, blood glucose and troponin T levels on admission than those with higher UNa. Plasma renin activity, aldosterone, cortisol and dopamine levels were also significantly higher in patients with lower UNa (all p < 0.001). Furthermore, patients with lower UNa had significantly less weight loss, lower net fluid loss/furosemide equivalent dose and higher incidence of worsening renal function during hospitalization than those with higher UNa (all p < 0.01). During a median follow-up period of 560 days, lower UNa was significantly associated with the composite of all-cause death and worsening heart failure (p < 0.001). In multivariable Cox-proportional hazards model, UNa remained an independent determinant of long-term adverse events (HR, 1.24, 95% CI, 1.06–1.45, p = 0.006). Conclusions Lower UNa was associated with worse long-term clinical outcomes along with increased neurohormonal activities, impaired response to diuretics and higher incidence of worsening renal function in patients with AHF.
  • Kazuhiro Nakao, Teruo Noguchi, Yasuhide Asaumi, Yoshiaki Morita, Tomoaki Kanaya, Masashi Fujino, Hayato Hosoda, Shuichi Yoneda, Shoji Kawakami, Toshiyuki Nagai, Kensaku Nishihira, Takahiro Nakashima, Reon Kumasaka, Tetsuo Arakawa, Fumiyuki Otsuka, Michio Nakanishi, Yu Kataoka, Yoshio Tahara, Yoichi Goto, Haruko Yamamoto, Toshimitsu Hamasaki, Satoshi Yasuda
    Trials 19 (1) 12 - 12 2018/01/08 [Refereed][Not invited]
     
    BACKGROUND: Despite the success of HMG-CoA reductase inhibitor (statin) therapy in reducing atherosclerotic cardiovascular events, a residual risk for cardiovascular events in patients with coronary artery disease (CAD) remains. Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are promising anti-atherosclerosis agents that might reduce the residual CAD risk. Non-contrast T1-weighted imaging (T1WI) with cardiac magnetic resonance (CMR) less invasively identifies high-risk coronary plaques as high-intensity signals. These high-intensity plaques (HIPs) are quantitatively assessed using the plaque-to-myocardium signal intensity ratio (PMR). Our goal is to assess the effect of EPA/DHA on coronary HIPs detected with T1WI in patients with CAD on statin treatment. METHODS/DESIGN: This prospective, controlled, randomized, open-label study examines the effect of 12 months of EPA/DHA therapy and statin treatment on PMR of HIPs detected with CMR and computed tomography angiography (CTA) in patients with CAD. The primary endpoint is the change in PMR after EPA/DHA treatment. Secondary endpoints include changes in Hounsfield units, plaque volume, vessel area, and plaque area measured using CTA. Subjects are randomly assigned to either of three groups: the 2 g/day EPA/DHA group, the 4 g/day EPA/DHA group, or the no-treatment group. DISCUSSION: This trial will help assess whether EPA/DHA has an anti-atherosclerotic effect using PMR of HIPs detected by CMR. The trial outcomes will provide novel insights into the effect of EPA/DHA on high-risk coronary plaques and may provide new strategies for lowering the residual risk in patients with CAD on statin therapy. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000015316 . Registered on 2 October 2014.
  • Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Yasuchika Takeishi, Kazuhiro Yamamoto, Hisao Ogawa, Toshihisa Anzai, JASPER Investigators
    Circulation Journal 82 (6) 1534 - 1545 1347-4820 2018 [Refereed][Not invited]
     
    Background: Despite the specific characteristics of heart failure with preserved ejection fraction (HFpEF) having been demonstrated predominantly from registries in Western countries, important international differences exist in terms of patient characteristics, management and medical infrastructure between Western and Asian countries. Methods and Results: We performed nationwide registration of consecutive Japanese hospitalized HFpEF patients with left ventricular EF ≥50% from 15 sites between November 2012 and March 2015. Follow-up data were obtained up to 2 years post-discharge. A total of 535 patients were registered. The median age was 80 years and 50% were female. The most common comorbid conditions were hypertension (77%) and atrial fibrillation (AF: 62%), but body mass index was relatively low. In-hospital mortality rate was 1.3% and the median length of hospitalization was 16 days. By 2 years post-discharge, 40.8% of patients had all-cause death or HF hospitalization. Approximately one-half of deaths had a cardiac cause. Lower serum albumin on admission was one of the strongest independent determinants of worse clinical outcome. Conclusions: Japanese HFpEF patients were less obese, but had a substantially higher prevalence of AF and lower incidence of subsequent events compared with previous reports. Our findings indicated that specific preventative and therapeutic strategies focusing on AF and nutritional status might need to be considered for Japanese hospitalized patients with HFpEF.
  • Toshiyuki Nagai, Varun Sundaram, Kieran Rothnie, Jennifer Kathleen Quint, Ahmad Shoaib, Yasuyuki Shiraishi, Shun Kohsaka, Susan Piper, Theresa A McDonagh, Suzanna Marie C Hardman, Ayumi Goda, Atsushi Mizuno, Takashi Kohno, Alan S Rigby, Tsutomu Yoshikawa, Andrew L Clark, Toshihisa Anzai, John G F Cleland
    Open heart 5 (2) e000811  2018 [Refereed][Not invited]
     
    Objective: Mortality amongst patients hospitalised for heart failure (HHF) in Western and Asian countries may differ, but this has not been investigated using individual patient-level data (IPLD). We sought to remedy this through rigorous statistical analysis of HHF registries and variable selection from a systematic literature review. Methods and results: IPLD from registries of HHF in Japan (n=3781) and the UK (n=894) were obtained. A systematic literature review identified 23 models for predicting outcome of HHF. Five variables appearing in 10 or more reports were strongly related to prognosis (systolic blood pressure, serum sodium concentration, age, blood urea nitrogen and creatinine). To compare mortality in the UK and Japan, variables were imputed in a propensity model using inverse probability of treatment weighting (IPTW) and IPTW with logistic regression (doubly robust IPTW). Overall, patients in the UK were sicker and in-patient and post-discharge mortalities were greater, suggesting that the threshold for hospital admission was higher. Covariate-adjusted in-hospital mortality was similar in the UK and Japan (IPTW OR: 1.14, 95% CI 0.70 to 1.86), but 180-day postdischarge mortality was substantially higher in the UK (doubly robust IPTW OR: 2.33, 95% CI 1.58 to 3.43). Conclusions: Despite robust methods to adjust for differences in patient characteristics and disease severity, HHF patients in the UK have roughly twice the mortality at 180 days compared with those in Japan. Similar analyses should be done using other data sets and in other countries to determine the consistency of these findings and identify factors that might inform healthcare policy and improve outcomes.
  • Mikio Shiba, Yasuo Sugano, Yoshihiko Ikeda, Hideshi Okada, Toshiyuki Nagai, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
    PloS one 13 (9) e0203756  2018 [Refereed][Not invited]
     
    AIMS: Left atrial (LA) structural remodelling develops in rheumatic heart disease (RHD) according to the disease severity of the mitral valve and the presence of atrial fibrillation. Sustained active inflammation has been previously reported in the LA of patients with RHD, suggesting a direct role of cell-mediated immunity in the pathogenesis of LA remodelling. Dendritic cells (DCs) have a major antigen-presenting role, and are known as crucial modulators of innate and adaptive immunity. We investigated whether DCs are involved in the pathogenesis of LA remodelling in RHD. METHODS AND RESULTS: Immunohistochemical analyses were performed using antibodies to CD11c, CD209 and CD80 as markers of myeloid DCs, migratory-active DCs, mature DCs and infiltrated inflammatory cells including T lymphocytes (CD3) and M1 (CD68; pro-inflammatory profile) and M2 (CD163; pro-resolution profile) macrophages. Furthermore, tenascin-C, an extracellular matrix (ECM) protein that appears during ECM remodelling and inflammatory response, was examined. Infiltrated myeloid DCs, migratory-active DCs, mature DCs and other inflammatory infiltrates including T lymphocytes and M1 and M2 macrophages, were significantly higher in the RHD group than the non-RHD group. The positive area fraction for tenascin-C was significantly higher in the RHD group than in the non-RHD group. CONCLUSION: Our histological findings suggest that inflammation may persist long after a bout of rheumatic fever, ultimately leading to ECM remodelling. We identified and quantitatively assessed several subsets of DCs and other immunocompetent cells, and our results indicated that activation of DCs has some role in persistence of LA inflammation in patients with chronic RHD.
  • Toshiyuki Nagai, Yasuyuki Honda, Hiroki Nakano, Satoshi Honda, Naotsugu Iwakami, Atsushi Mizuno, Nobuyuki Komiyama, Takafumi Yamane, Yutaka Furukawa, Tadayoshi Miyagi, Syuzo Nishihara, Nobuhiro Tanaka, Taichi Adachi, Toshimitsu Hamasaki, Yasuhide Asaumi, Yoshio Tahara, Takeshi Aiba, Yasuo Sugano, Hideaki Kanzaki, Teruo Noguchi, Kengo Kusano, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
    CARDIOVASCULAR DRUGS AND THERAPY 31 (5-6) 551 - 557 0920-3206 2017/12 [Refereed][Not invited]
     
    Despite current therapies, acute heart failure (AHF) remains a major public health burden with high rates of in-hospital and post-discharge morbidity and mortality. Carperitide is a recombinantly produced intravenous formulation of human atrial natriuretic peptide that promotes vasodilation with increased salt and water excretion, which leads to reduction of cardiac filling pressures. A previous open-label randomized controlled study showed that carperitide improved long-term cardiovascular mortality and heart failure (HF) hospitalization for patients with AHF, when adding to standard therapy. However, the study was underpowered to detect a difference in mortality because of the small sample size. Low-dose Administration of Carperitide for Acute Heart Failure (LASCAR-AHF) is a multicenter, randomized, open-label, controlled study designed to evaluate the efficacy of intravenous carperitide in hospitalized patients with AHF. Patients hospitalized for AHF will be randomly assigned to receive either intravenous carperitide (0.02 mu g/kg/min) in addition to standard treatment or matching standard treatment for 72 h. The primary end point is death or rehospitalization for HF within 2 years. A total of 260 patients will be enrolled between 2013 and 2018. The design of LASCAR-AHF will provide data of whether carperitide reduces the risk of mortality and rehospitalization for HF in selected patients with AHF.
  • Atsuko Yanagida, Takahiro Iizuka, Toshiyuki Nagai, Ryo Usui, Juntaro Kaneko, Tsugio Akutsu, Ritsuko Hanajima, Naomi Kanazawa, Kazutoshi Nishiyama
    JOURNAL OF THE NEUROLOGICAL SCIENCES 382 40 - 43 0022-510X 2017/11 [Refereed][Not invited]
  • Naoya Asakawa, Keisuke Uchida, Mamoru Sakakibara, Kazunori Omote, Keiji Noguchi, Yusuke Tokuda, Kiwamu Kamiya, Kanako C. Hatanaka, Yoshihiro Matsuno, Shiro Yamada, Kyoko Asakawa, Yuichiro Fukasawa, Toshiyuki Nagai, Toshihisa Anzai, Yoshihiko Ikeda, Hatsue Ishibashi-Ueda, Masanori Hirota, Makoto Orii, Takashi Akasaka, Kenta Uto, Yasushige Shingu, Yoshiro Matsui, Shin-Ichiro Morimoto, Hiroyuki Tsutsui, Yoshinobu Eishi
    PLOS ONE 12 (7) e0179980  1932-6203 2017/07 [Refereed][Not invited]
     
    Background Although rare, cardiac sarcoidosis (CS) is potentially fatal. Early diagnosis and intervention are essential, but histopathologic diagnosis is limited. We aimed to detect Propionibacterium acnes, a commonly implicated etiologic agent of sarcoidosis, in myocardial tissues obtained from CS patients. Methods and results We examined formalin-fixed paraffin-embedded myocardial tissues obtained by surgery or autopsy and endomyocardial biopsy from patients with CS (n = 26; CS-group), myocarditis (n = 15; M-group), or other cardiomyopathies (n = 39; CM-group) using immunohistochemistry (IHC) with a P. acnes-specific monoclonal antibody. We found granulomas in 16 (62%) CS-group samples. Massive (>= 14 inflammatory cells) and minimal (< 14 inflammatory cells) inflammatory foci, respectively, were detected in 16 (62%) and 11 (42%) of the CS-group samples, 10 (67%) and 10 (67%) of the M-group samples, and 1 (3%) and 18 (46%) of the CM-group samples. P. acnes-positive reactivity in granulomas, massive inflammatory foci, and minimal inflammatory foci were detected in 10 (63%), 10 (63%), and 8 (73%) of the CS-group samples, respectively, and in none of the M-group and CMgroup samples. Conclusions Frequent identification of P. acnes in sarcoid granulomas of originally aseptic myocardial tissues suggests that this indigenous bacterium causes granuloma in many CS patients. IHC detection of P. acnes in massive or minimal inflammatory foci of myocardial biopsy samples without granulomas may be useful for differentiating sarcoidosis from myocarditis or other cardiomyopathies.
  • Atsushi Okada, Yasuo Sugano, Toshiyuki Nagai, Yasuyuki Honda, Naotsugu Iwakami, Hiroki Nakano, Seiji Takashio, Satoshi Honda, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Satoshi Yasuda, Toshihisa Anzai
    AMERICAN JOURNAL OF CARDIOLOGY 119 (12) 2035 - 2041 0002-9149 2017/06 [Refereed][Not invited]
     
    Abnormal liver function test results are often observed in acute decompensated heart failure (ADHF). However, the prognostic value of bilirubin fractionation has not been elucidated. The prognostic value of direct bilirubin (DB), in comparison with total bilirubin (TB), was examined in 556 consecutive patients with ADHF. Patients with elevated DB showed mostly similar patient characteristics including signs of elevated right-sided pressure (frequent hepatomegaly, jugular venous distention, dilated inferior vena cava, and elevated gammaglutamyltransferase) and decreased cardiac output (cold extremities, decreased pulse pressure, and lower blood pressure) and other parameters of heart failure (HF) severity (increased plasma renin activity, decreased sodium, total cholesterol, and ejection fraction) to elevated TB; however, only patients with elevated DB showed a significant difference in the frequency of HF history and alkaline phosphatase value. Kaplan-Meier analysis showed that patients with elevated DB had a significantly higher rate of the composite end point of all-cause mortality or HF readmission (p = 0.021) compared with those with normal DB, whereas patients with elevated TB did not show a statistically significant difference compared with those with normal TB (INS). A multivariate Cox hazards model showed that DB was an independent predictor of adverse events (adjusted hazard ratio 1.052, 95% confidence interval 1.001 to 1.099, p = 0.034), whereas TB was not (adjusted hazard ratio 1.017, 95% confidence interval 0.985 to 1.046, p = 0.27). Adding DB to existing prognostic variables resulted in higher C-statistics than adding TB (C-statistics: 0.670 to 0.675, 0.670 to 0.674, respectively). In conclusion, elevated DB in ADHF was an independent prognostic predictor that was superior to TB. DB may be useful for further risk stratification in ADHF. (C) 2017 Elsevier Inc. All rights reserved.
  • Takafumi Nakayama, Yasuo Sugano, Tetsuro Yokokawa, Toshiyuki Nagai, Taka-aki Matsuyama, Keiko Ohta-Ogo, Yoshihiko Ikeda, Hatsue Ishibashi-Ueda, Takeshi Nakatani, Nobuyuki Ohte, Satoshi Yasuda, Toshihisa Anzai
    EUROPEAN JOURNAL OF HEART FAILURE 19 (4) 490 - 498 1388-9842 2017/04 [Refereed][Not invited]
     
    Background Dilated cardiomyopathy (DCM) is the most common cardiomyopathy and causes left ventricular enlargement and contractile dysfunction, with a poor prognosis. The mechanisms underlying the disease process have not been precisely identified, but recent evidence has suggested that the activation of myocardial inflammation is involved in the deterioration associated with the condition. Methods and results Biopsy samples from 182 consecutive DCM patients were immunohistochemically stained with antibodies specific to CD3 (T lymphocytes), CD68 (whole macrophages), and CD163 (M2 macrophages), and each type of infiltrating cell was counted. Masson's trichrome staining was used to determine the collagen area fraction (CAF) in each sample. Patients were followed up for 6.9 +/- 2.4 years, and their clinical data were obtained for analysis. Median (interquartile range) numbers of myocardial CD3, CD68, and CD163-cell infiltrates were 8.1 (4.0-14.2)/mm(2), 22.3 (12.1-36.0)/mm(2), and 6.5 (2.0-14.0)/mm(2), respectively. Patients with higher counts of infiltrating CD3-, CD68-, and CD163-positive cells had significantly poorer outcomes (P = 0.007, P = 0.011, and P = 0.022, respectively). A high CD163-positive infiltrate count was independently associated with worse outcome in multivariate Cox regression analysis (hazard ratio 1.77, P = 0.004), and multivariate linear regression analysis revealed that the CD163 cell count was an independent determinant of CAF (P < 0.001). Conclusions It was found that DCM with increased myocardial immune activation was associated with poor long-term outcome. The association between M2 macrophages and collagen formation suggests the phenotypic polarization of macrophages toward M2 may be associated with ventricular remodelling in DCM.
  • Seiji Takashio, Toshiyuki Nagai, Yasuo Sugano, Satoshi Honda, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo F. Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
    PLOS ONE 12 (4) e0173336  1932-6203 2017/04 [Refereed][Not invited]
     
    Background High-sensitive cardiac troponin T (hsTnT) is a sensitive biomarker of myocardial damage and predictor of acute decompensated heart failure (ADHF). However, there is little information on changes over time in hsTnT level during ADHF management. The aim of this prospective study was to evaluate changes in hsTnT levels between admission and at discharge in patients with ADHF, and identify factors that determine such levels and their prognostic significance. Methods and results We evaluated 404 ADHF patients with abnormal hsTnT levels (>0.0135 ng/ml) on admission. The median (interquartile ranges) hsTnT levels on admission, at discharge, and percent changes in hsTnT levels were 0.038 (0.026 to 0.065), 0.032 (0.021 to 0.049) ng/ml, and -12.0 (-39.8 to 7.4) % respectively. The numbers of patients with falling (hsTnT decrease > -15%), stable (hsTnT change between-15 and +15%) and rising (hsTnT increase > +15%) hsTnT level at discharge were 190, 146, and 68, respectively. The percent change in B-type natriuretic peptide (BNP) levels was greater in the falling group, compared to the stable (p<0.001) and rising groups (p<0.001). Changes in hsTnT levels correlated significantly with changes in BNP levels (p = 0.22, p<0.001). Multivariate Cox regression analysis identified rising or stable hsTnT at discharge as a significant predictor of heart failure-related rehospitalization (hazard ratio: 1.69; 95% confidence interval: 1.06 to 2.70; p = 0.03). Conclusions Persistent increase in hsTnT levels at discharge correlated with inadequate decrease of BNP levels, and was a predictor of poor clinical outcome, with repeat heart failure hospitalizations.
  • Yu Kataoka, Mariko Harada-Shiba, Kazuhiro Nakao, Takahiro Nakashima, Shoji Kawakami, Masashi Fujino, Tomoaki Kanaya, Toshiyuki Nagai, Yoshio Tahara, Yasuhide Asaumi, Mika Hori, Masatsune Ogura, Yoichi Goto, Teruo Noguchi, Satoshi Yasuda
    JOURNAL OF CLINICAL LIPIDOLOGY 11 (2) 413 - 421 1933-2874 2017/04 [Refereed][Not invited]
     
    BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9), an important contributor to low-density lipoprotein metabolism in heterozygous familial hypercholesterolemia (HeFH), exhibits direct proatherogenic effects. PCSK9 circulates as mature and furin-cleaved forms, which differ in its biological activity. However, it remains to be elucidated whether each PCSK9 subtype has different atherogenic properties. OBJECTIVE: To investigate the association of each PCSK9 subtype with coronary atherosclerosis in HeFH. METHODS: About 204 nonculprit segments in 138 HeFH subjects with coronary artery disease were evaluated by using intravascular ultrasound. Mature, furin-cleaved PCSK9 and total concentration of PCSK9 subtypes were measured by using enzyme-linked immunosorbent assay (BML Inc., Tokyo, Japan). The relationship of these PCSK9 values with intravascular ultrasound measures was investigated. RESULTS: Mature PCSK9 level was positively associated with percent atheroma volume (PANT: r = 0.78, P =.003). Despite extensive atheroma under a higher mature PCSK9 level, vessel volume did not change across any mature PCSK9 levels (r = 0.05, P = .78). These responses resulted in smaller lumen volume, which was negatively correlated to mature PCSK9 level (r = 0.65, P = .009). By contrast, there were no significant relationships of PAV with furin-cleaved (r = 0.12, P = .45) and total PCSK9 (r = 0.37, P = .25) levels. On multivariate analysis, mature PCSK9 level independently contributed to PAV (odds ratio: 1.45, 95% confidence interval: 1.11-1.67, P = .01). Even in subjects with low-density lipoprotein cholesterol level <2.6 mmol/L, greater PAV was still observed in association with an elevated mature PCSK9 level (P = .003). CONCLUSIONS: Mature PCSK9 associated with atheroma volume and impaired vessel remodeling in HeFH patients with coronary artery disease. These findings suggest the potential role of mature PCSK9 in propagation of coronary atherosclerosis in HeFH. (C) 2017 National Lipid Association. All rights reserved.
  • 低体重は駆出率が保持された心不全における転帰の独立予測因子である JASPER試験からの報告(Underweight is an Independent Predictor of Outcomes in Heart Failure with Preserved Ejection Fraction: A Report from JASPER Study)
    Matsumoto Junichi, Kinugawa Shintaro, Fukushima Arata, Yokota Takashi, Yoshikawa Tsutomu, Saito Yoshihiko, Nagai Toshiyuki, Anzai Toshihisa
    日本循環器学会学術集会抄録集 81回 LBCS3 - 6 2017/03
  • Naotsugu Iwakami, Toshiyuki Nagai, Toshiaki A. Furukawa, Yasuo Sugano, Satoshi Honda, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
    INTERNATIONAL JOURNAL OF CARDIOLOGY 230 529 - 536 0167-5273 2017/03 [Refereed][Not invited]
     
    Background: The prognostic value of nutritional status is poorly understood and evidence-based nutritional assessment indices are required in acute heart failure (AHF). We investigated the prognostic value of malnutrition assessed by the Controlling Nutritional Status (CONUT) score (range 0-12, higher = worse, consisting of serum albumin, cholesterol and lymphocytes) in AHF patients. Methods: The CONUT score was measured on admission in 635 consecutive AHF patients. The primary outcome was all-cause death. Results: Median CONUT score was 3 (interquartile range 2 to 5). During the median follow-up of 324 days, CONUT score was independently associated with death (HR 1.26, 95% CI 1.11-1.42, P < 0.001) after adjustment for confounders in a multivariate Cox model. The CONUT score demonstrated the best C-statistic for predicting death (0.71) among other common nutritional markers in HF. Furthermore, addition of the CONUT score to an established risk prediction model from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure study significantly increased the C-statistic from 0.75 to 0.77 (P = 0.02). The net reclassification improvement afforded by CONUT score was 21% for all-cause death, 27% for survival and 49% overall (P < 0.001). Conclusion: Malnutrition assessed by the CONUT score on admission was an independent determinant of long-term death in AHF, and its prognostic value outweighed that of other nutritional indices. Moreover, addition of the score to the existing risk prediction model significantly increased the predictive ability for death, indicating beneficial clinical application of the CONUT score in AHF patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Yasuyuki Honda, Toshiyuki Nagai, Yasuo Sugano, Satoshi Honda, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
    AMERICAN JOURNAL OF CARDIOLOGY 119 (4) 604 - 610 0002-9149 2017/02 [Refereed][Not invited]
     
    The echo Doppler end-diastolic pulmonary regurgitation (EDPR) gradient correlates well with catheter-derived pulmonary artery diastolic pressure. An elevated EDPR gradient is associated with worse clinical outcomes in patients with stable coronary artery disease. However, the prognostic significance of EDPR gradient in patients with heart failure (HF) is unclear. The aim of the present study was to investigate the prognostic impact of EDPR gradient in HF. We retrospectively examined 751 consecutive hospitalized patients with acute HF. Those with acute coronary syndrome or in-hospital death and those without accessible EDPR gradient data at discharge were excluded. Finally, 265 patients were examined and divided into 2 groups according to EDPR gradient (cutoff 9 mm Hg). Adverse events were defined as worsening HF and death. Patients with elevated EDPR gradient had higher B-type natriuretic peptide, lower age, and lower left ventricular ejection fraction at discharge than those with nonelevated EDPR gradient. During a median followup Of 429 days, elevated EDPR gradient was independently associated with adverse events (hazard ratio 2.34, 95% CI 1.44 to 3.78, p <0.001) after adjustment for confounders. In conclusion, echo Doppler EDPR gradient might be a noninvasive predictor of clinical outcomes in hospitalized patients with HF. (C) 2016 Elsevier Inc. All rights reserved.
  • Satoshi Honda, Toshiyuki Nagai, Toshihisa Anzai
    INTERNATIONAL JOURNAL OF CARDIOLOGY 229 133 - 133 0167-5273 2017/02 [Refereed][Not invited]
  • Noriaki Moriyama, Masaharu Ishihara, Teruo Noguchi, Michio Nakanishi, Tetsuo Arakawa, Yasuhide Asaumi, Leon Kumasaka, Tomoaki Kanaya, Toshiyuki Nagai, Masashi Fujino, Satoshi Honda, Reiko Fujiwara, Toshihisa Anzai, Kengo Kusano, Yoichi Goto, Satoshi Yasuda, Shigeru Saito, Hisao Ogawa
    JOURNAL OF CARDIOLOGY 69 (1-2) 79 - 83 0914-5087 2017/01 [Refereed][Not invited]
     
    Background: Acute kidney injury (AKI) often occurs in patients with acute myocardial infarction (AMI), and is associated with adverse outcomes. However, it remains unclear how timing of AKI affects it. This study assessed impact of timing of AKI on prognosis after AMI. Methods: This study consisted of 760 patients with AMI who were admitted within 48 h after symptom onset. AKI was diagnosed as increase in creatinine >= 0.3 mg/dl or >= 50% within any 48 h after admission. Patients were classified into 3 groups according to the occurrence and timing of AKI: no-AKI, early-AKI (within 48 h after admission) and late-AKI (>48 h). Early-AKI was classified into transient early-AKI, defined as creatinine returning to the level below the criteria of AKI, and persistent early-AKI. Results: Early-AKI occurred in 64 patients (9%) and late-AKI in 32 patients (4%). Patients with early-AKI had significantly higher mortality (35%) than those with late-AKI (7%, p < 0.001) and no-AKI (3%, p < 0.001). Multivariate analysis showed early-AKI was an independent predictor of in-hospital mortality (OR: 3.38, 95% CI: 1.30-8.76, p = 0.013), but late-AKI was not. Among patients with early-AKI, mortality was significantly higher even if AKI was transient (23%, p < 0.001). Patients with persistent early-AKI had the highest mortality (66%, p < 0.001). Conclusions: Early-AKI was associated with worse outcome. Even if renal function once returned to baseline level, patients with early-AKI tended to be at high risk of mortality. (C) 2016 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.
  • Takahito Doi, Yu Kataoka, Teruo Noguchi, Tatsuhiro Shibata, Takahiro Nakashima, Shoji Kawakami, Kazuhiro Nakao, Masashi Fujino, Toshiyuki Nagai, Tomoaki Kanaya, Yoshio Tahara, Yasuhide Asaumi, Etsuko Tsuda, Michikazu Nakai, Kunihiro Nishimura, Toshihisa Anzai, Kengo Kusano, Hiroaki Shimokawa, Yoichi Goto, Satoshi Yasuda
    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 37 (12) 2350 - + 1079-5642 2017 [Refereed][Not invited]
     
    Objective-Coronary artery ectasia (CAE) is an infrequently observed vascular phenotype characterized by abnormal vessel dilatation and disturbed coronary flow, which potentially promote thrombogenicity and inflammatory reactions. However, whether or not CAE influences cardiovascular outcomes remains unknown. Approach and Results-We investigated major adverse cardiac events (MACE; defined as cardiac death and nonfatal myocardial infarction [MI]) in 1698 patients with acute MI. The occurrence of MACE was compared in patients with and without CAE. CAE was identified in 3.0% of study subjects. During the 49-month observation period, CAE was associated with 3.25-, 2.71-, and 4.92-fold greater likelihoods of experiencing MACE (95% confidence interval [CI], 1.88-5.66; P<0.001), cardiac death (95% CI, 1.37-5.37; P=0.004), and nonfatal MI (95% CI, 2.20-11.0; P<0.001), respectively. These cardiac risks of CAE were consistently observed in a multivariate Cox proportional hazards model (MACE: hazard ratio, 4.94; 95% CI, 2.36-10.4; P<0.001) and in a propensity score-matched cohort (MACE: hazard ratio, 8.98; 95% CI, 1.14-71.0; P=0.03). Despite having a higher risk of CAE-related cardiac events, patients with CAE receiving anticoagulation therapy who achieved an optimal percent time in target therapeutic range, defined as >= 60%, did not experience the occurrence of MACE (P=0.03 versus patients with percent time in target therapeutic range <60% or without anticoagulation therapy). Conclusions-The presence of CAE predicted future cardiac events in patients with acute MI. Our findings suggest that acute MI patients with CAE are a high-risk subset who might benefit from a pharmacological approach to controlling the coagulation cascade. Visual Overview-An online visual overview is available for this article.
  • Satoshi Honda, Toshiyuki Nagai, Yasuo Sugano, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
    INTERNATIONAL JOURNAL OF CARDIOLOGY 222 521 - 527 0167-5273 2016/11 [Refereed][Not invited]
     
    Background: Delirium is a serious syndrome in critically ill patients. However, the prognostic impact of delirium and its determinants in acute heart failure (AHF) patients have not been fully elucidated. Methods: We examined 611 AHF patients who were admitted to our institution. Delirium was diagnosed based on the Intensive Care Delirium Screening Checklist (ICDSC). Results: Delirium developed in 139 patients (23%) during hospitalization. Patients with delirium had higher incidence of non-cardiovascular death (p = 0.046) and worsening heart failure (p < 0.001) during hospitalization. Among patients who survived at discharge, the incidence of all-cause death, cardiovascular death and non-cardiovascular death after discharge were significantly higher in patients with delirium than those without (log-rank; p < 0.001, p = 0.001, p < 0.001, respectively) during a median follow-up period of 335 days. In multivariable model, the development of delirium was an independent determinant of worsening heart failure during hospitalization (OR: 2.44, 95% CI: 1.27-4.63) and all-cause death after discharge (HR: 2.38, 95% CI: 1.30-4.35). Furthermore, multivariate analysis indicated that history of cerebrovascular disease (OR: 2.13, 95% CI: 1.36-3.35), age (OR: 1.43, 95% CI: 1.15-1.80), log BNP (OR: 1.39, 95% CI: 1.09-1.79), serum albumin (OR: 0.84, 95% CI: 0.76-0.93) and blood glucose levels (OR: 1.03, 95% CI: 1.00-1.06) were independent determinants of delirium. Conclusion: In patients with AHF, the development of delirium was associated with poor clinical outcomes, suggesting the importance of early screening and careful monitoring of delirium in such patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Toshiyuki Nagai, Yasuyuki Honda, Yasuo Sugano, Kunihiro Nishimura, Michikazu Nakai, Satoshi Honda, Naotsugu Iwakami, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
    PLOS ONE 11 (11) e0165841  1932-6203 2016/11 [Refereed][Not invited]
     
    Background irculating polyunsaturated fatty acid (PUFA) levels are associated with clinical outcomes in cardiovascular diseases including coronary artery disease and chronic heart failure (HF). However, their clinical implications in acute decompensated HF (ADHF) remain unclear. The aim of this study was to investigate the clinical roles of circulating PUFAs in patients with ADHF. Methods Circulating levels of PUFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA) and dihomo-gamma linoleic acid (DGLA), were measured on admission in 685 consecutive ADHF patients. Adverse events were defined as all-cause death and worsening HF. Results During a median follow-up period of 560 days, 262 (38.2%) patients had adverse events. Although patients with adverse events had lower n-6 PUFA (AA + DGLA) level than those without, n-3 PUFA (EPA + DHA) level was comparable between the groups. Kaplan-Meier analyses showed that lower n-6 PUFA level on admission was significantly associated with the composite of all-cause death and worsening HF, all-cause death, cardiovascular death and worsening HF (p < 0.001, p = 0.005, p = 0.021, p = 0.019, respectively). In a multivariate Cox model, lower n-6 PUFA level was independently associated with increased risk of adverse events (HR 0.996, 95% CI: 0.993 - 0.999, p = 0.027). Conclusions Lower n-6 but not n-3 PUFA level on admission was significantly related to worse clinical outcomes in ADHF patients. Measurement of circulating n-6 PUFA levels on admission might provide information for identifying high risk ADHF patients.
  • Yasuyuki Honda, Toshiyuki Nagai, Yoshihiko Ikeda, Mamoru Sakakibara, Naoya Asakawa, Nobutaka Nagano, Michikazu Nakai, Kunihiro Nishimura, Yasuo Sugano, Keiko Ohta-Ogo, Yasuhide Asaumi, Takeshi Aiba, Hideaki Kanzaki, Kengo Kusano, Teruo Noguchi, Satoshi Yasuda, Hiroyuki Tsutsui, Hatsue Ishibashi-Ueda, Toshihisa Anzai
    JOURNAL OF THE AMERICAN HEART ASSOCIATION 5 (11) 2047-9980 2016/11 [Refereed][Not invited]
     
    Background-The histological diagnosis of cardiac sarcoidosis (CS) is based on the presence of myocardial granulomas; however, the sensitivity of endomyocardial biopsy is relatively low. We investigated whether immunocompetent cells including dendritic cells (DC) and macrophages in nongranuloma sections of endomyocardial biopsy samples could be histopathological surrogates for CS diagnosis. Methods and Results-The numbers of DC and macrophages were investigated in 95 consecutive CS patients and 50 patients with nonischemic cardiomyopathy as controls. All patients underwent endomyocardial biopsy, and immunohistochemical staining was performed on all samples. We examined these immunocompetent cells in nongranuloma sections in CS patients diagnosed by the presence of myocardial granulomas (n=26) and in CS patients without myocardial granulomas diagnosed by the Japanese Ministry of Health Welfare 2007 criteria (n=65) or the Heart Rhythm Society 2014 criteria (n=26). In CS patients with and without myocardial granulomas, CD209(+) DC and CD68(+) macrophages were more frequently observed (P< 0.01) and CD163(+) M2 macrophages were less frequently observed (P< 0.01) in nongranuloma sections compared to controls. Furthermore, the combination of decreased CD163+ M2/CD68(+) macrophage ratio and increased number of CD209+ DC in nongranuloma sections of CS patients demonstrated high specificity (100%, 95% CI 92.7-100) for CS diagnosis with each diagnostic criteria and the presence of myocardial granulomas. Conclusions-Increased number of DC and decreased M2 among all macrophages in nongranuloma sections of myocardium showed high specificity for CS diagnosis, suggesting DC and macrophage phenotypes as histopathological surrogates for the diagnosis of CS.
  • Tadayoshi Miyagi, Yasuhide Asaumi, Kunihiro Nishimura, Takahiro Nakashima, Hiroki Sakamoto, Kazuhiro Nakao, Tomoaki Kanaya, Toshiyuki Nagai, Yuji Shimabukuro, Yoshihiro Miyamoto, Tomoyuki Fujita, Kengo Kusano, Toshihisa Anzai, Junjirou Kobayashi, Teruo Noguchi, Hisao Ogawa, Satoshi Yasuda
    CIRCULATION-CARDIOVASCULAR INTERVENTIONS 9 (9) 1941-7640 2016/09 [Refereed][Not invited]
     
    Background The efficacy and prognosis of percutaneous coronary intervention (PCI) as secondary revascularization in patients with previous coronary artery bypass graft surgery remain uncertain. Methods and Results We retrospectively evaluated 434 consecutive patients with previous coronary artery bypass graft surgery hospitalized for PCI between 2004 and 2011 (men 84%, age 71 (interquartile range, 66-76) years) and calculated the coronary artery bypass graft Synergy Between Percutaneous Coronary Intervention With Taxus score (CSS) before (baseline CSS) and after PCI (post-PCI CSS). Patients were divided into 2 groups based on median post-PCI CSS: low-score (23; n=217) and high-score groups (>23; n=217). Major adverse cardiovascular events (MACE) were defined as the composite of cardiovascular death, myocardial infarction, and unplanned repeat revascularization for myocardial ischemia. The median baseline and post-PCI CSS were 30 (interquartile range, 21-40) and 23 (interquartile range, 14.5-33.5), respectively. During a median follow-up of 69 months, the prevalence of MACE and cardiac death differed significantly between the 2 post-PCI CSS groups (MACE: low, 13.8%; high, 28.6%; P<0.001; cardiac death: low, 6.2%; high, 16.7%; P=0.002). In multivariable analysis, the high post-PCI CSS divided by the median was associated with substantially greater cumulative MACE (hazard ratio, 2.09; 95% confidence interval, 1.31-3.34; P=0.002) and cardiac death (hazard ratio, 2.02; 95% confidence interval, 1.03-3.98; P=0.042) compared with the low post-PCI CSS. Net reclassification improvement analysis revealed that post-PCI CSS resulted in significantly improved prediction of MACE and cardiac death compared with baseline CSS. Conclusions In this external validation study, the CSS was a potential prognostic factor after subsequent PCI, even for previous coronary artery bypass graft surgery patients.
  • Toshiyuki Nagai, Toshihisa Anzai
    Nihon rinsho. Japanese journal of clinical medicine 74 Suppl 6 340 - 4 0047-1852 2016/08 [Refereed][Not invited]
  • Yasuyuki Honda, Toshiyuki Nagai, Naotsugu Iwakami, Yasuo Sugano, Satoshi Honda, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
    AMERICAN JOURNAL OF CARDIOLOGY 118 (4) 550 - 555 0002-9149 2016/08 [Refereed][Not invited]
     
    Malnutrition is becoming one of the most important determinants of worse clinical outcomes in patients with acute heart failure (AHF). However, appropriate tools for evaluating the nutritional status in patients aged >= 65 years with AHF remain unclear. We examined 490 consecutive patients aged >= 65 years with AHF. They were divided into 2 groups according to Geriatric Nutritional Risk Index (GNRI; cut-off value = 92). During a median period of 189 days, the mortality rate was significantly higher in the lower GNRI group than the higher GNRI group (p <0.001). In multivariate analyses, lower GNRI was an independent determinant of adverse events (FIR 0.92, 95% CI 0.88 to 0.95, p <0.001). The GNRI showed the best prognostic value (C-statistic: 0.70) among other nutritional indexes. Adding GNRI to an existing outcome prediction model for mortality in AHF significantly increased the C-statistic from 0.68 to 0.74 (p = 0.017). The net reclassification improvement afforded by GNRI was 60% overall, 27% for events, and 33% for nonevents (p <0.001). In conclusion, lower GNRI on admission was independently associated with worse clinical outcomes in patients aged >= 65 years with AHF, and it was superior to other nutritional parameters. Furthermore, the assessment of nutritional status using GNRI is very helpful for risk stratification. (C) 2016 Elsevier Inc. All rights reserved.
  • Yasuhiro Hamatani, Hatsue Ishibashi-Ueda, Toshiyuki Nagai, Yasuo Sugano, Hideaki Kanzaki, Satoshi Yasuda, Tomoyuki Fujita, Junjiro Kobayashi, Toshihisa Anzai
    PLOS ONE 11 (8) e0160208  1932-6203 2016/08 [Refereed][Not invited]
     
    Background Congenital bicuspid aortic valve (CBAV) is the main cause of aortic stenosis (AS) in young adults. However, the histopathological features of AS in patients with CBAV have not been fully investigated. Methods and Results We examined specimens of aortic valve leaflets obtained from patients who had undergone aortic valve re/placement at our institution for severe AS with CBAV (n = 24, CBAV-AS group), severe AS with tricuspid aortic valve (n = 24, TAV-AS group), and severe aortic regurgitation (AR) with CBAV (n = 24, CBAV-AR group). We compared the histopathological features among the three groups. Pathological features were classified using semiquantitative methods (graded on a scale 0 to 3) by experienced pathologists without knowledge of the patients' backgrounds. The severity of inflammation, neovascularization, and calcium and cholesterol deposition did not differ between the CBAV-AS and TAV-AS groups, and these four parameters were less marked in the CBAV-AR group than in the CBAV-AS (all p< 0.01). Meanwhile, the grade of valvular fibrosis was greater in the CBAVAS group, compared with the TAV-AS and CBAV-AR groups (both p< 0.01). In AS patients, thickness of fibrotic lesions was greater on the aortic side than on the ventricular side (both p< 0.01). Meanwhile, thickness of fibrotic lesions was comparable between the aortic and ventricular sides in CBAV-AR patients (p = 0.35). Conclusions Valvular fibrosis, especially on the aortic side, was greater in patients with CBAV-AS than in those without, suggesting a difference in the pathogenesis of AS between CBAV and TAV.
  • Nagai T, Anzai T
    Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology 74 Suppl 6 340 - 344 0911-4300 2016/08 [Refereed][Not invited]
  • Toshiyuki Nagai, Kunihiro Nishimura, Takehiro Honma, Aya Higashiyama, Yasuo Sugano, Michikazu Nakai, Satoshi Honda, Naotsugu Iwakami, Atsushi Okada, Shoji Kawakami, Tomoaki Kanaya, Yasuhide Asaumi, Takeshi Aiba, Yoko Nishida, Yoshimi Kubota, Daisuke Sugiyama, Tomonori Okamura, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
    EUROPEAN JOURNAL OF HEART FAILURE 18 (7) 803 - 813 1388-9842 2016/07 [Refereed][Not invited]
     
    Aims Although previous reports suggest that an elevated endogenous erythropoietin (EPO) level is associated with worse clinical outcomes in chronic heart failure (HF) patients, the prognostic implication of EPO in patients with acute decompensated HF (ADHF) and underlying mechanisms of the high EPO level in severe HF patients who have a poor prognosis remain unclear. Methods and results We examined 539 consecutive ADHF patients with EPO measurement on admission from our registry. During a median follow-up period of 329 days, a higher EPO level on admission was independently associated with worse clinical outcomes [hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.06-1.48, P = 0.008], and haemoglobin level was the strongest determinant of EPO level (P < 0.001), whereas estimated glomerular filtration rate (eGFR) was not significant in multivariate regression analysis. In the anaemic subgroup of 318 patients, a higher EPO level than expected on the basis of their haemoglobin level was related to increased adverse events (HR 1.63, 95% CI 1.05-2.49, P = 0.028). Moreover, estimated plasma volume excess rate was positively associated with EPO level (P = 0.003), and anaemic patients with a higher than expected EPO level tended to have a higher estimated plasma volume excess rate and plasma lactate level, and lower systemic oxygen saturation level with the preservation of the reticulocyte production index than those with a lower than expected EPO level. Conclusion A high EPO level predicts long-term worse clinical outcomes in ADHF patients, independent of anaemia and impaired renal function. Anaemia and hypoxia due to severe congestion may synergistically contribute to a high EPO level in high-risk HF patients.
  • Tetsuro Yokokawa, Yasuo Sugano, Akito Shimouchi, Atsushi Shibata, Naoya Jinno, Toshiyuki Nagai, Hideaki Kanzaki, Takeshi Aiba, Kengo Kusano, Mikiyasu Shirai, Yasuchika Takeishi, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
    CIRCULATION JOURNAL 80 (5) 1178 - 1186 1346-9843 2016/05 [Refereed][Not invited]
     
    Background: We hypothesized that exhaled acetone concentration (EAC), reflecting altered blood ketone body metabolism and increased acetone exhaust because of pulmonary congestion in heart failure (HF), would correlate with hemodynamic parameters in patients with non-ischemic chronic HF. Methods and Results: We prospectively enrolled 102 non-ischemic HF patients with New York Heart Association (NYHA) class I-III. Exhaled breath was collected after an overnight fast. Echocardiography and cardiac catheterization were performed in all patients. We also enrolled 17 control patients without HF. EAC in the HF patients was significantly higher than that in the control patients (median EAC; 0.53 vs. 0.38 ppm, P=0.012). EAC positively correlated with blood total ketone bodies (r=0.454, P<0.001), NYHA class (r=0.489, P<0.001), and plasma B-type natriuretic peptide (r=0.316, P=0.001). Right heart catheterization revealed that EAC significantly correlated with pulmonary capillary wedge pressure (PCWP, r=0.377, P<0.001). Receiver-operating characteristic analysis revealed that EAC >1.05 ppm was associated with PCWP >= 18 mmHg (area under the curve [AUC] 0.726, sensitivity 50%, specificity 89%). EAC was shown to be a comparable diagnostic biomarker for HF to BNP (AUC 0.760, sensitivity 80%, specificity 70%). Conclusions: EAC may be a novel noninvasive biomarker that correlates hemodynamic severity in non-ischemic chronic HF.
  • Tetsuro Yokokawa, Yasuo Sugano, Takafumi Nakayama, Toshiyuki Nagai, Taka-aki Matsuyama, Keiko Ohta-Ogo, Yoshihiko Ikeda, Hatsue Ishibashi-Ueda, Takeshi Nakatani, Satoshi Yasuda, Yasuchika Takeishi, Hisao Ogawa, Toshihisa Anzai
    EUROPEAN JOURNAL OF HEART FAILURE 18 (4) 375 - 385 1388-9842 2016/04 [Refereed][Not invited]
     
    AimDilated cardiomyopathy (DCM) has a variety of causes, and no useful approach to predict left ventricular (LV) remodelling and long-term outcome has yet been established. Myocardial tenascin-C (TNC) is known to appear under pathological conditions, possibly to regulate cardiac remodelling. The aim of this study was to clarify the significance of myocardial TNC expression in LV remodelling and the long-term outcome in DCM. Methods and resultsOne hundred and twenty-three consecutive DCM patients who underwent endomyocardial biopsy for initial diagnosis were studied. Expression of TNC in biopsy sections was analysed immunohistochemically to quantify the ratio of the TNC-positive area to the whole myocardial tissue area (TNC area). Clinical parameters associated with TNC area were investigated. The patients were divided into two groups based on receiver operating characteristic analysis of TNC area to predict death: high TNC group with TNC area 2.3% (22 patients) and low TNC group with TNC area <2.3% (101 patients). High TNC was associated with diabetes mellitus. Comparing echocardiographic findings between before and 9months after endomyocardial biopsy, the low TNC group was associated with decreased LV end-diastolic diameter and increased LV ejection fraction, whereas the high TNC group was not. Survival analysis revealed a worse outcome in the high TNC group than in the low TNC group (P<0.001). Multivariable Cox regression analysis revealed that TNC area was independently associated with poor outcome (HR=1.347, P=0.032). ConclusionsIncreased myocardial TNC expression was associated with worse LV remodeling and long-term outcome in DCM.
  • Atsushi Okada, Yasuo Sugano, Toshiyuki Nagai, Seiji Takashio, Satoshi Honda, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo F. Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
    CIRCULATION JOURNAL 80 (4) 913 - 923 1346-9843 2016/04 [Refereed][Not invited]
     
    Background: There are limited studies regarding the prognostic value of coagulation abnormalities in heart failure patients. The clinical significance of prothrombin time international normalized ratio (INR), a widely accepted marker assessing coagulation abnormalities, in acute decompensated heart failure (ADHF) remains unclear. Methods and Results: Among 561 consecutive patients admitted for ADHF, INR was assessed in 294 patients without prior anticoagulation therapy, acute coronary syndrome, liver disease, or overt disseminated intravascular coagulation. Increased INR on admission was positively associated with increased levels of thrombin-antithrombin complex, C-reactive protein, total bilirubin, gamma-glutamyl transpeptidase, inferior vena cava diameter, tricuspid regurgitation severity, markers of neurohormonal activation, and also negatively associated with decreased albumin, cholinesterase, and total cholesterol. In contrast, there was no significant association with left ventricular ejection fraction, serum sodium or blood urea nitrogen. Multivariate analysis showed that increased INR was independently associated with increased all-cause mortality (hazard ratio 1.89 per 0.1 increase, 95% confidence interval 1.14-3.13, P=0.013) during the median follow up of 284 days. Increased INR also had a higher prognostic value compared to risk score models including the Model for End-Stage Liver Disease (MELD) score or the MELD excluding INR (MELD-XI) score. Conclusions: Increased INR is an independent predictor of all-cause mortality in ADHF patients without anticoagulation, reflecting coagulation abnormalities and hepatic insufficiency, possibly through systemic inflammation, neurohormonal activation and venous congestion.
  • Toshiyuki Nagai, Nobutaka Nagano, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Hideaki Kanzaki, Kengo Kusano, Teruo Noguchi, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
    AMERICAN JOURNAL OF CARDIOLOGY 117 (6) 966 - 971 0002-9149 2016/03 [Refereed][Not invited]
     
    Prednisolone (PSL) therapy is the gold standard treatment in patients with cardiac sarcoidosis (CS). However, clinicians often have difficulty in deciding whether to discontinue PSL therapy in long-term management. Sixty-one consecutive patients with CS were divided into 2 groups based on the discontinuation of PSL during the median follow-up period of 9.9 years. PSL was discontinued in 12 patients because of improvement of clinical findings. There were no significant differences between the 2 groups in age, gender, left ventricular ejection fraction (LVEF), findings of imaging techniques, incidence of fatal arrhythmias and heart failure, and dose of PSL. After discontinuation of PSL, 5 patients had cardiac death, and discontinuation of PSL was significantly associated with higher cardiac mortality compared with continuation (p = 0.035). Although patients with discontinuation had improvement of LVEF after PSL treatment, LVEF decreased after discontinuation of PSL. Furthermore, discontinuation of PSL was associated with greater percent decrease in LVEF compared with continuation (p = 0.037) during the follow-up period. In conclusion, in the long-term management of patients with CS, discontinuation of PSL was associated with poor clinical outcomes and decreased LVEF, suggesting the importance of PSL maintenance therapy. (c) 2016 Elsevier Inc. All rights reserved.
  • Teruo Noguchi, Satoshi Yasuda, Tatsuhiro Shibata, Shoji Kawakami, Tomotaka Tanaka, Yasuhide Asaumi, Tomoaki Kanaya, Toshiyuki Nagai, Kazuhiro Nakao, Masashi Fujino, Kazuyuki Nagatsuka, Hatsue Ishibashi-Ueda, Kunihiro Nishimura, Yoshihiro Miyamoto, Kengo Kusano, Toshihisa Anzai, Yoichi Goto, Hisao Ogawa
    CIRCULATION 133 (5) E379 - E379 0009-7322 2016/02 [Refereed][Not invited]
  • Toshiyuki Nagai, Nobutaka Nagano, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Hideaki Kanzaki, Kengo Kusano, Teruo Noguchi, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
    CIRCULATION JOURNAL 79 (7) 1593 - 1600 1346-9843 2015/07 [Refereed][Not invited]
     
    Background: Cardiac involvement is the worst prognostic determinant in patients with sarcoidosis, but the long-term prognostic significance of corticosteroid therapy for cardiac sarcoidosis (CS) remains unclear. Methods and Results: We examined 83 consecutive patients diagnosed with CS. Patients were divided into 2 groups based on the presence or absence of corticosteroid therapy at diagnosis. Patients with corticosteroid therapy had lower age and higher rate of positive findings in the myocardium on gallium scintigraphy (Ga) at diagnosis than those without. LVEF, biomarkers, and use of cardiovascular medication were similar between the 2 groups. During the follow-up (7.6 +/- 4.4 years), corticosteroid therapy was associated with fewer long-term adverse events (overall, P=0.005; cardiac death, P=0.92; symptomatic arrhythmias, P=0.89; heart failure admission, P<0.0001) and a greater % increase in LVEF than those without (7.9 +/- 36.3% vs. -16.7 +/- 34.8%, P=0.03). On Cox proportional hazards modeling, corticosteroid therapy (HR, 0.41; 95% CI: 0.20-0.89) was an independent determinant of long-term adverse event-free survival, but age, sex, LVEF, and Ga findings were not. Conclusions: Corticosteroid therapy might have a beneficial effect on long-term clinical outcome in CS patients, particularly by reduction of heart failure admission and retarding the progression of LV systolic dysfunction.
  • Nobutaka Nagano, Toshiyuki Nagai, Yasuo Sugano, Yoshiaki Morita, Yasuhide Asaumi, Takeshi Aiba, Hideaki Kanzaki, Kengo Kusano, Teruo Noguchi, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
    CIRCULATION JOURNAL 79 (7) 1601 - 1608 1346-9843 2015/07 [Refereed][Not invited]
     
    Background: Basal thinning of the interventricular septum (IVS) is an important diagnostic feature of cardiac sarcoidosis (CS), but its long-term prognostic significance remains unclear. Methods and Results: We examined 74 consecutive patients who were diagnosed with CS. Basal IVS thickness at a point located 10 mm from the aortic annulus was measured. IVS thickness at the left ventricular minor axis level (IVS) was also measured according to the recommended procedure of the American Society of Echocardiography. Patients were divided into 2 groups based on the presence or absence of basal IVS thinning, which was defined as basal IVS <= 4 mm and/or basal IVS/IVS ratio <= 0.6. Basal IVS thinning was observed in 21 patients and was associated with greater long-term adverse events during follow-up (5.1 +/- 2.5 years), although the baseline characteristics were comparable between groups (overall, P<0.01; all-cause death, P=0.53; symptomatic arrhythmias, P<0.01; heart failure admission, P=0.027). Multivariate analysis showed basal IVS thinning was an independent determinant of long-term adverse events (hazard ratio 2.86, 95% confidence interval 1.31-6.14) even after adjustment for existing prognostic variables. Conclusions: The presence of basal IVS thinning at the time of CS diagnosis was associated with poor long-term clinical outcomes, suggesting its prognostic significance in patients with CS.
  • Tatsuhiro Shibata, Shoji Kawakami, Teruo Noguchi, Tomotaka Tanaka, Yasuhide Asaumi, Tomoaki Kanaya, Toshiyuki Nagai, Kazuhiro Nakao, Masashi Fujino, Kazuyuki Nagatsuka, Hatsue Ishibashi-Ueda, Kunihiro Nishimura, Yoshihiro Miyamoto, Kengo Kusano, Toshihisa Anzai, Yoichi Goto, Hisao Ogawa, Satoshi Yasuda
    CIRCULATION 132 (4) 241 - 250 0009-7322 2015/07 [Refereed][Not invited]
     
    Background-Coronary artery embolism (CE) is recognized as an important nonatherosclerotic cause of acute myocardial infarction. Its prevalence, clinical features, and prognosis remain insufficiently characterized. Methods and Results-We screened 1776 consecutive patients who presented with de novo acute myocardial infarction between 2001 and 2013. CE was diagnosed based on criteria encompassing histological, angiographic, and other diagnostic imaging findings. The prevalence, clinical characteristics, treatment strategies, in-hospital outcomes, and long-term risk of CE recurrence or major adverse cardiac and cerebrovascular events (cardiac death, fatal arrhythmia, or recurrent thromboembolism) were evaluated. The prevalence of CE was 2.9% (n=52), including 8 (15%) patients with multivessel CE. Atrial fibrillation was the most common cause (n=38, 73%). Only 39% of patients with CE were treated with vitamin K antagonists, and the median international normalized ratio was 1.42 (range, 0.95-1.80). Eighteen of the 30 CE patients with nonvalvular atrial fibrillation had a CHADS(2) score of 0 or 1. When those patients were reevaluated using CHA(2)DS(2)-VASc, 61% were reassigned to a higher risk category. During a median follow-up of 49 months, CE and thromboembolism recurred in 5 atrial fibrillation patients. The 5-year rate of major adverse cardiac and cerebrovascular events was 27.1%. In the propensity score-matched cohorts (n=45 each), Kaplan-Meier analysis showed a significantly higher incidence of cardiac death in the CE group than in the non-CE group (hazard ratio, 9.29; 95% confidence interval, 1.13-76.5; P<0.001). Conclusions-Atrial fibrillation is the most frequent cause of CE. Patients with CE represent a high-risk subgroup of patients with acute myocardial infarction and require close follow-up.
  • Yasuhide Asaumi, Teruo Noguchi, Yoshiaki Morita, Reiko Fujiwara, Tomoaki Kanaya, Taka-aki Matsuyama, Tomohiro Kawasaki, Masashi Fujino, Takafumi Yamane, Toshiyuki Nagai, Tadayoshi Miyagi, Hatsue Ishibashi-Ueda, Masahiro Higashi, Yoshiaki Komori, Masaharu Ishihara, Hisao Ogawa, Satoshi Yasuda
    JACC-CARDIOVASCULAR IMAGING 8 (6) 741 - 743 1936-878X 2015/06 [Refereed][Not invited]
  • Toshiyuki Nagai, Shun Kohsaka, Keiichi Fukuda
    CHEST 147 (3) E119 - E119 0012-3692 2015/03 [Refereed][Not invited]
  • UEMURA KAZUNORI, Chinen Daigo, Nagai Toshiyuki, Kawada Toru, Yasuda Satoshi, Sugimachi Masaru
    Transactions of Japanese Society for Medical and Biological Engineering 一般社団法人 日本生体医工学会 53 S156_03 - S156_03 2015 
    Assessing left ventricular (LV) filling pressure (pulmonary capillary wedge pressure, PCWP) is essential in the care of patients with heart failure (HF). Physicians use right ventricular (RV) filling pressure such as central venous pressure (CVP) to predict PCWP. However, the use of this method is limited because discordance between CVP and PCWP is sometimes observed. Our theoretical analysis indicated that PCWP can be predicted by CVP corrected by the relation between RV and LV function, provided by the ratio of tissue-Doppler systolic velocity of tricuspid annulus (ST) to that of mitral annulus (SM) (CVP·ST/SM). In 16 HF dogs, a stronger correlation was observed between CVP·ST/SM and PCWP than between CVP and PCWP. This was also confirmed in 98 HF patients. Furthermore, when ultrasonic dimension of inferior vena cava (IVCD) was used as a noninvasive alternative to CVP in the HF patients, a stronger correlation was observed between IVCD·ST/SM and PCWP than between the early diastolic transmitral inflow to mitral annular velocity ratio (E/e') and PCWP. RV filling pressure or its noninvasive surrogate such as IVCD corrected by ST/SM may be useful to predict PCWP in HF patients.
  • Yasuhide Asaumi, Teruo Noguchi, Yoshiaki Morita, Taka-Aki Matsuyama, Fumiyuki Otsuka, Reiko Fujiwara, Tomoaki Kanaya, Toshiyuki Nagai, Masahiro Higashi, Kengo Kusano, Toshihisa Anzai, Hatsue Ishibashi-Ueda, Hisao Ogawa, Satoshi Yasuda
    CIRCULATION JOURNAL 79 (1) 218 - 220 1346-9843 2015/01 [Refereed][Not invited]
  • Masashi Fujino, Masaharu Ishihara, Satoshi Honda, Shoji Kawakami, Takafumi Yamane, Toshiyuki Nagai, Kazuhiro Nakao, Tomoaki Kanaya, Leon Kumasaka, Yasuhide Asaumi, Tetsuo Arakawa, Yoshio Tahara, Michio Nakanishi, Teruo Noguchi, Kengo Kusano, Toshihisa Anzai, Yoichi Goto, Satoshi Yasuda, Hisao Ogawa
    AMERICAN JOURNAL OF CARDIOLOGY 114 (12) 1789 - 1793 0002-9149 2014/12 [Refereed][Not invited]
     
    This study was undertaken to assess the impact of acute hyperglycemia (acute-HG) and chronic hyperglycemia (chronic-HG) on short-term outcomes, in patients with acute myocardial infarction (AMI). This study consisted of 696 patients with AMI. Acute-HG was defined as admission plasma glucose >= 200 mg/dl and chronic-HG as hemoglobin A1c >= 6.5%. Acute-HG was associated with higher peak serum creatine kinase (4,094 +/- 4,594 vs 2,526 +/- 2,227 IU/L, p <0.001) and in-hospital mortality (9.8% vs 1.6%, p <0.001). On the contrary, there was no significant difference in peak creatine kinase (2,803 +/- 2,661 vs 2,940 +/- 3,181 IU/L, p = 0.59) and mortality (3.3 vs 3.7%, p = 0.79) between patients with chronic-HG and those without. Multivariate analysis showed that admission plasma glucose was an independent predictor of in-hospital mortality (odds ratio 1.15, 95% confidence interval 1.05 to 1.27, p <0.001), but hemoglobin A1c was not. When only patients with acute-HG were analyzed, chronic-HG was associated with a significantly smaller infarct size (3,221 +/- 3,001 vs 5,904 +/- 6,473 IU/L, p <0.001) and lower in-hospital mortality (5.5 vs 18.9%, p = 0.01). In conclusion, these results suggested that acute-HG, but not chronic-HG, was associated with adverse short-term outcomes after AMI. Paradoxically, in patients with acute-HG, chronic-HG might abate the adverse effects of acute-HG. (C) 2014 Elsevier Inc. All rights reserved.
  • Toshiyuki Nagai, Shun Kohsaka, Shigeo Okuda, Toshihisa Anzai, Koichiro Asano, Keiichi Fukuda
    CHEST 146 (4) 1064 - 1072 0012-3692 2014/10 [Refereed][Not invited]
     
    BACKGROUND: Cardiac death is the leading cause of mortality associated with sarcoidosis in Japan. However, the involvement of sarcoidosis infiltration oft en remains undetected. Recently, late gadolinium enhancement with cardiovascular MRI (LGE-CMR) imaging has been introduced for the detection of myocardial infiltrative disease, as it enables the detection of even minor myocardial damage. We investigated the incidence and prognostic value of LGE-CMR in patients with extracardiac sarcoidosis without cardiac manifestations. METHODS: Sixty-one consecutive patients who met the histologic and clinical criteria for sarcoidosis, and who did not have signs or symptoms of cardiovascular involvement, were prospectively recruited. LGE-CMR was performed at the time of enrollment, and patients were classified into positive or negative late gadolinium enhancement groups based on the findings. The study end point was a composite of all-cause death, symptomatic arrhythmia, and heart failure necessitating admission. RESULTS: Patients were predominantly middle aged (57 +/- 15 years) and female (66%), and most had stable disease activity that did not require treatment with immunosuppressants. LGE-CMR detected cardiac involvement in eight patients (13%). Interventricular septal thinning detected by echocardiography was an independent predictor of LGE-CMR-detected cardiac involvement. During the follow-up period of 50 + 12 months, no significant difference in adverse events was noted between patients in the LGE-CMR-positive and LGE-CMR-negative groups. CONCLUSIONS: LGE-CMR detected cardiac involvement in 13% of patients with sarcoidosis without cardiac manifestation, but both patients with and without LGE had relatively low event rates.
  • Satoshi Honda, Yasuhide Asaumi, Takafumi Yamane, Toshiyuki Nagai, Tadayoshi Miyagi, Teruo Noguchi, Toshihisa Anzai, Yoichi Goto, Masaharu Ishihara, Kunihiro Nishimura, Hisao Ogawa, Hatsue Ishibashi-Ueda, Satoshi Yasuda
    JOURNAL OF THE AMERICAN HEART ASSOCIATION 3 (5) e000984  2047-9980 2014/10 [Refereed][Not invited]
     
    Background-There is little known about whether the clinical and pathological characteristics and incidence of cardiac rupture (CR) in patients with acute myocardial infarction (AMI) have changed over the years. Methods and Results-The incidence and clinical characteristics of CR were investigated in patients with AMI, who were divided into 3 cohorts: 1977-1989, 1990-2000, and 2001-2011. Of a total of 5699 patients, 144 were diagnosed with CR and 45 survived. Over the years, the incidence of CR decreased (1977-1989, 3.3%; 1990-2000, 2.8%; 2001-2011, 1.7%; P=0.002) in association with the widespread adoption of reperfusion therapy. The mortality rate of CR decreased (1977-1989, 90%; 1990-2000, 56%; 2001-2011, 50%; P=0.002) in association with an increase in the rate of emergent surgery. In multivariable analysis, first myocardial infarction, anterior infarct, female sex, hypertension, and age >70 years were significant risk factors for CR, whereas impact of hypertension on CR was weaker from 2001 to 2011. Primary percutaneous coronary intervention (PPCI) was a significant protective factor against CR. In 64 autopsy cases with CR, myocardial hemorrhage occurred more frequently in those who underwent PPCI or fibrinolysis than those who did not receive reperfusion therapy (no reperfusion therapy, 18.0%; fibrinolysis, 71.4%; PPCI, 83.3%; P=0.001). Conclusions-With the development of medical treatment, the incidence and mortality rate of CR have decreased. However, first myocardial infarction, anterior infarct, female sex, and old age remain important risk factors for CR. Adjunctive cardioprotection against reperfusion-induced myocardial hemorrhage is emerging in the current PPCI era.
  • Noriaki Moriyama, Masaharu Ishihara, Teruo Noguchi, Michio Nakanishi, Tetsuo Arakawa, Yasuhide Asaumi, Leon Kumasaka, Tomoaki Kanaya, Tadayoshi Miyagi, Toshiyuki Nagai, Takafumi Yamane, Masashi Fujino, Satoshi Honda, Reiko Fujiwara, Toshihisa Anzai, Kengo Kusano, Yoichi Goto, Satoshi Yasuda, Hisao Ogawa
    CIRCULATION JOURNAL 78 (6) 1475 - 1480 1346-9843 2014/06 [Refereed][Not invited]
     
    Background: Acute kidney injury (AKI) and acute hyperglycemia are associated with unfavorable outcomes. The impact of acute hyperglycemia on the development of AKI after acute myocardial infarction (AMI), however, remains unclear. This study was undertaken to assess the relationship between admission glucose and incidence of AKI after AMI. Methods and Results: This study consisted of 760 patients with AMI admitted to the National Cerebral and Cardiovascular Center within 48 h after symptom onset. Blood sample was obtained on admission and repeated sampling was done at least every 1 or 2 days during the first week. AKI was diagnosed as increase in serum creatinine >= 0.3 mg/dl or >= 50% within any 48 h. Ninety-six patients (13%) had AKI during hospitalization for AMI, and these patients had higher in-hospital mortality than those without AKI (25% vs. 3%, P < 0.001). Patients with AKI had higher plasma glucose (PG) on admission than those without (222 +/- 105 mg/dl vs. 166 +/- 69 mg/dl, P < 0.001). The incidence of AKI increased as admission PG rose: 7% with PG < 120 mg/dl; 9% with PG 120-160 mg/dl; 11% with PG 160-200 mg/dl; and 28% with PG >200 mg/dl (P < 0.01). On multivariate analysis admission PG was an independent predictor of AKI (odds ratio, 1.10; 95% confidence interval: 1.03-1.18, P = 0.02). Conclusions: Admission hyperglycemia might have contributed to the development of AKI in patients with AMI.
  • Toshiyuki Nagai, Satoshi Honda, Yasuo Sugano, Taka-aki Matsuyama, Keiko Ohta-Ogo, Yasuhide Asaumi, Yoshihiko Ikeda, Kengo Kusano, Masaharu Ishihara, Satoshi Yasuda, Hisao Ogawa, Hatsue Ishibashi-Ueda, Toshihisa Anzai
    JOURNAL OF THE AMERICAN HEART ASSOCIATION 3 (3) e000839  2047-9980 2014/06 [Refereed][Not invited]
     
    Background-Dendritic cells (DC) play pivotal roles in regulating the immune system and inflammatory response. We previously reported DC infiltration in the infarcted heart and its immunoprotective roles in the post-infarction healing process after experimental myocardial infarction (MI). However, its clinical significance has not been determined. Methods and Results-The degree of DC infiltration and its correlation with the post-infarction healing process in the human infarcted heart were investigated in 24 autopsy subjects after ST-elevation MI. Patients were divided into two groups according to the presence (n=13) or absence (n=11) of cardiac rupture. The numbers of infiltrated DC and macrophages and the extent of fibrosis in the infarcted area were examined. In the rupture group, CD68(+) macrophage infiltration was increased and CD209(+) DC, and CD11c(+) DC infiltration and the extent of reparative fibrosis were decreased compared with the non-rupture group, under matched baseline characteristics including the time from onset to death and use of revascularization. Furthermore, there was a significant positive correlation between the number of infiltrating CD209(+) DC, and CD11c(+) DC and the extent of reparative fibrosis. Conclusions-Decreased number of DC in human-infarcted myocardial tissue was associated with increased macrophage infiltration, impaired reparative fibrosis, and the development of cardiac rupture after MI. These findings suggest a protective role of DC in post-MI inflammation and the subsequent healing process.
  • Noriaki Moriyama, Masaharu Ishihara, Teruo Noguchi, Michio Nakanishi, Tetsuo Arakawa, Yasuhide Asaumi, Leon Kumasaka, Tomoaki Kanaya, Tadayoshi Miyagi, Toshiyuki Nagai, Takafumi Yamane, Masashi Fujino, Satoshi Honda, Reiko Fujiwara, Toshihisa Anzai, Kengo Kusano, Yoichi Goto, Satoshi Yasuda, Hisao Ogawa
    CIRCULATION JOURNAL 78 (6) 1475 - 1480 1346-9843 2014/06 [Refereed][Not invited]
     
    Background: Acute kidney injury (AKI) and acute hyperglycemia are associated with unfavorable outcomes. The impact of acute hyperglycemia on the development of AKI after acute myocardial infarction (AMI), however, remains unclear. This study was undertaken to assess the relationship between admission glucose and incidence of AKI after AMI. Methods and Results: This study consisted of 760 patients with AMI admitted to the National Cerebral and Cardiovascular Center within 48 h after symptom onset. Blood sample was obtained on admission and repeated sampling was done at least every 1 or 2 days during the first week. AKI was diagnosed as increase in serum creatinine >= 0.3 mg/dl or >= 50% within any 48 h. Ninety-six patients (13%) had AKI during hospitalization for AMI, and these patients had higher in-hospital mortality than those without AKI (25% vs. 3%, P < 0.001). Patients with AKI had higher plasma glucose (PG) on admission than those without (222 +/- 105 mg/dl vs. 166 +/- 69 mg/dl, P < 0.001). The incidence of AKI increased as admission PG rose: 7% with PG < 120 mg/dl; 9% with PG 120-160 mg/dl; 11% with PG 160-200 mg/dl; and 28% with PG >200 mg/dl (P < 0.01). On multivariate analysis admission PG was an independent predictor of AKI (odds ratio, 1.10; 95% confidence interval: 1.03-1.18, P = 0.02). Conclusions: Admission hyperglycemia might have contributed to the development of AKI in patients with AMI.
  • Toshiyuki Nagai, Takuro Hirano, Mayumi Tsunoda, Haruhiko Hosaka, Yoshikazu Kishino, Takaharu Katayama, Keisuke Matsumura, Takashi Miyagawa, Shun Kohsaka, Toshihisa Anzai, Keiichi Fukuda, Masahiro Suzuki
    HEART AND VESSELS 28 (5) 559 - 565 0910-8327 2013/09 [Refereed][Not invited]
     
    Despite the positive impact of percutaneous coronary intervention (PCI) on reducing mortality, a small percentage of patients experience poor myocardial reperfusion following PCI. However, factors associated with no-reflow remain unclear. We investigated clinical factors associated with no-reflow following PCI for coronary artery disease (CAD). We retrospectively analyzed 1622 consecutive CAD patients who underwent PCI over a 5-year period at our institution. Patients were divided into two groups according to the presence (n = 31) or absence (n = 1591) of no-reflow, defined as Thrombolysis in Myocardial Infarction flow grade < 3 after PCI. No significant differences in patient characteristics or PCI strategy were seen between the no-reflow and normal flow groups. The incidence of no-reflow was significantly lower in the left circumflex artery (LCx) than in the left anterior descending artery (LAD) (P = 0.0015), with no differences in characteristics or PCI strategy between these two target vessels. Multivariate analysis revealed that involvement of the LCx was an independent protective factor against no-reflow (odds ratio 0.14, 95 % confidence interval 0.02-0.98, P = 0.044). In conclusion, LCx as the target vessel was protective against no-reflow compared with LAD following PCI for CAD. Our results suggest that embolic protection devices may be unnecessary in CAD patients with involvement of LCx.
  • Toshiyuki Nagai, Toshihisa Anzai, Yoshinori Mano, Hidehiro Kaneko, Atsushi Anzai, Yasuo Sugano, Yuichiro Maekawa, Toshiyuki Takahashi, Tsutomu Yoshikawa, Keiichi Fukuda
    HEART AND VESSELS 28 (3) 404 - 411 0910-8327 2013/05 [Refereed][Not invited]
     
    Serum C-reactive protein (CRP) elevation is associated with poor clinical outcome in patients with heart failure (HF). We previously reported that CRP exacerbates the development of pressure overload-induced cardiac remodeling through an enhanced inflammatory response and oxidative stress. In the present study, we examined the effect of eicosapentaenoic acid (EPA), a suppressor of inflammatory response and oxidative stress, on pressure overload-induced cardiac remodeling. Transverse aortic constriction (TAC) was performed on transgenic mice overexpressing CRP (CRPtg) and nontransgenic littermates (TAC/CON). CRPtg with TAC operation were randomly assigned to be fed a standard diet (TAC/CRPtg) or an EPA-enriched diet (7 % of total energy) (TAC/CRPtg/EPA). Myocardial mRNA level of transforming growth factor-beta 1, proinflammatory cytokines, and oxidative stress markers were increased in TAC/CRPtg in comparison with TAC/CON 1 and 4 weeks after the operation. These parameters were significantly suppressed in TAC/CRPtg/EPA compared with TAC/CRPtg. In addition, after 4 weeks of EPA treatment, as compared with TAC/CRPtg, TAC/CRPtg/EPA mice demonstrated reduced heart and lung weights, increased left ventricular fractional shortening, and decreased left ventricular end-diastolic pressure, together with decreased cardiac hypertrophy, fibrosis, and improved cardiac function. In conclusion, the anti-inflammatory and antioxidative properties of EPA may make it an effective therapeutic strategy for adverse cardiac remodeling associated with CRP overexpression.
  • Shun Kohsaka, Toshiyuki Nagai, Makito Yaegashi, Keiichi Fukuda
    HEPATOLOGY RESEARCH 42 (4) 433 - 434 1386-6346 2012/04 [Refereed][Not invited]
  • Shun Kohsaka, Masashi Goto, Toshiyuki Nagai, Vei-Vei Lee, MacArthur Elayda, Yutaka Furukawa, Masanori Fukushima, Masashi Komeda, Ryuzo Sakata, Mitsuru Ohsugi, Keiichi Fukuda, James M. Wilson, Toru Kita, Takeshi Kimura
    DIABETES CARE 35 (3) 654 - 659 0149-5992 2012/03 [Refereed][Not invited]
     
    OBJECTIVE-Approximately 25% of patients who undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) have diabetes, and the diagnosis of diabetes roughly doubles the mortality risk associated with coronary artery disease. However, the impact of diabetes may differ according to ethnicity. Our objective was to examine the impact of diabetes on long-term survival among U.S. and Japanese patients who underwent PCI or CABG. RESEARCH DESIGN AND METHODS-For the current analysis, we included 8,871 patients from a Japanese multicenter registry (Coronary Revascularization Demonstrating Outcome database in Kyoto; median follow-up 3.5 years; interquartile range [IQR] 2.6-4.3) and 7,229 patients from a U.S. multipractice registry (Texas Heart Institute Research Database; median follow-up 5.2 years; IQR 3.8-6.5). RESULTS-Diabetes was more prevalent among Japanese than U.S. patients (39.2 vs. 31.0%; P < 0.001). However, after revascularization, long-term all-cause mortality was lower in diabetic Japanese patients than in diabetic U.S. patients (85.4 vs. 82.2%; log-rank test P = 0.009), whereas it was similar in nondiabetic Japanese and U.S. patients (89.1 vs. 89.5%; P = 0.50). The national difference in crude mortality was also significant among insulin-using patients with diabetes (80.8 vs. 74.9%; P = 0.023). When long-term mortality was adjusted for known predictors, U.S. location was associated with greater long-term mortality risk than Japanese location among nondiabetic patients (hazard ratio 1.58 [95% CI 1.32-1.88]; P <0.001) and, especially, diabetic patients (1.88 [1.54-2.30]; P < 0.001). CONCLUSIONS-Although diabetes was less prevalent in U.S. patients than in Japanese patients, U.S. patients had higher overall long-term mortality risk. This difference was more pronounced in diabetic patients. Diabetes Care 35:654-659, 2012
  • Toshiyuki Nagai, Shun Kohsaka, Toshihisa Anzai, Tsutomu Yoshikawa, Keiichi Fukuda, Toru Sato
    CHEST 141 (1) 272 - 273 0012-3692 2012/01 [Refereed][Not invited]
  • Toshiyuki Nagai, Shun Kohsaka, Mitsushige Murata, Shigeo Okuda, Toshihisa Anzai, Keiichi Fukuda, Toru Satoh
    INTERNAL MEDICINE 51 (17) 2277 - 2283 0918-2918 2012 [Refereed][Not invited]
     
    Objective We sought to determine the value of electrocardiographic right ventricular hypertrophy (ECG-RVH) in pulmonary hypertension (PH) patients with right ventricular systolic dysfunction defined by cardiac magnetic resonance (CMR-RVSD). Patients A total of 31 consecutive patients with PH with a mean pulmonary arterial pressure of >25 mmHg underwent both ECG and CMR studies. Patients were divided into 2 groups according to the presence of RVSD, defined as a RV ejection fraction <35%. Logistic regression modeling was performed to define the association between ECG-RVH and CMR-RVSD. Results About half of the patients had RVSD (n=15; 48%). The R to S wave ratio (p=0.01) or incidence of qR pattern (p=0.002) in lead V1 was significantly greater in patients with PH complicated by RVSD than in those without RVSD. These 2 patterns were significant predictors of RVSD [ odds ratio (OR), 19.3 for qR; OR, 14.0 for R/S>1] and when each of these ECG findings was assigned with a point proportional to OR (score of 2 for qR in lead V1 and score of 1 for R/S>1 in lead V1), the incidence of RVSD increased by the total ECG score. Conclusion The combination of ECG-RVH findings, especially in lead V1, predicts the presence of RVSD defined by CMR. ECG might be a useful tool for estimating the presence of RVSD in patients with PH.
  • Yutaka Hitomi, Toshiyuki Nagai, Masahito Kodera
    CHEMICAL COMMUNICATIONS 48 (84) 10392 - 10394 1359-7345 2012 [Refereed][Not invited]
     
    We have synthesised a silver(I) complex with a metal-arene interaction, where the anthracene ring of the ligand sidearm is positioned above the silver(I) ion. The interaction is disrupted by ethylene coordination to the silver(I). The reversible interconversion between the metal-arene and metal-ethylene interactions allowed us to monitor the presence of ethylene.
  • Nagai T, Yoshikawa T
    Nihon rinsho. Japanese journal of clinical medicine 69 Suppl 9 126 - 132 0047-1852 2011/11 [Refereed][Not invited]
  • Hidehiro Kaneko, Toshihisa Anzai, Keisuke Horiuchi, Takashi Kohno, Toshiyuki Nagai, Atsushi Anzai, Toshiyuki Takahashi, Aya Sasaki, Masayuki Shimoda, Yuichiro Maekawa, Hideyuki Shimizu, Tsutomu Yoshikawa, Yasunori Okada, Ryohei Yozu, Keiichi Fukuda
    ATHEROSCLEROSIS 218 (2) 470 - 478 0021-9150 2011/10 [Refereed][Not invited]
     
    Objective: Tumor necrosis factor (TNF)-alpha is known to be elevated in plasma and the aorta in abdominal aortic aneurysm (AAA) patients. We sought to clarify the role of TNF-alpha converting enzyme (Tace), which cleaves the transmembrane precursor of TNF-alpha, in AAA development. Methods: We obtained aortic sample of AAA during surgical operation to assess the histological features and protein expression of human AAA. AAA was induced in mice with temporal systemic deletion of Tace by the inducible Mx-1 Cre transgene (TaceMx1) and in wild-type littermates (CON) by periaortic application of CaCl(2) (AAA/TaceMx1, AAA/CON). Results: Tace expression was increased in human AAA samples as compared with normal aorta. Six weeks postoperatively, aortic diameter in AAA/TaceMx1 was decreased than in AAA/CON in association with attenuated TNF-alpha expression and extracellular matrix disruption. Increased activities of matrix metalloproteinase (MMP)-9 and MMP-2, numbers of Mac-2-positive macrophages, CD3-positive T lymphocytes and CD31-positive vessels in periaortic tissues, mRNA expression of CD68, monocyte chemotactic protein-1, TNF-alpha, vascular endothelial growth factor-A, p47 and glutathione peroxidases, and protein expression of phospho-c-Jun N-terminal kinase in AAA were all attenuated by Tace deletion. Protein expression of transforming growth factor (TGF)-beta 1 was upregulated by Tace deletion in sham-operated mice. TGF-beta 1 expression was further increased in AAA/TaceMx1. Conclusions: Tace was overexpressed in the aortic wall in human and experimental AAA. Temporal systemic deletion of Tace prevented AAA development in association with attenuating inflammation, oxidative stress, neoangiogenesis and extracellular matrix disruption, suggesting a crucial role of Tace in AAA development. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
  • Hidehiro Kaneko, Toshihisa Anzai, Keisuke Horiuchi, Kokichi Morimoto, Atsushi Anzai, Toshiyuki Nagai, Yasuo Sugano, Yuichiro Maekawa, Hiroshi Itoh, Tsutomu Yoshikawa, Yasunori Okada, Satoshi Ogawa, Keiichi Fukuda
    CIRCULATION JOURNAL 75 (10) 2482 - 2490 1346-9843 2011/10 [Refereed][Not invited]
     
    Background: Tumor necrosis factor (TNF)-alpha, which is released as a soluble form by ectodomain shedding of TNF-alpha converting enzyme (Tace), is known to play a pivotal role in obesity-induced insulin resistance. The role of lace in obesity-induced metabolic disorders was to be clarified in this study. Methods and Results: Transgenic mice with temporal systemic lace deletion (TaceMx1) and their non-transgenic littermates (CON) were fed a standard diet or a high-fat diet (HFD) from 6 weeks of age. The increased body, liver and epididymal adipose tissue (EAT) weights, systolic blood pressure, and fasting glucose and lipid levels and decreased serum adiponectin level 12 weeks after starting a HFD were suppressed by Tace inactivation. A HFD/TaceMx1 showed ameliorated glucose tolerance and insulin sensitivity compared with HFD/CON. Indirect calorimetry showed that energy expenditure and oxidation of both fat and carbohydrate were higher in HFD/TaceMx1 than HFD/CON. Marked hepatosteatosis, increased triglyceride content and TNF-alpha expression in liver, and increased adipocyte size, macrophage infiltration and TNF-alpha and monocyte chemoattractant protein-1 expression in EAT induced by a HFD were attenuated in HFD/TaceMx1. Conclusions: Inactivation of Tace suppressed HFD-induced obesity, insulin resistance, hepatosteatosis and adipose tissue remodeling in association with increased energy expenditure, suggesting an important role of lace in the development of obesity-induced metabolic disorders. (Circ J 2011; 75: 2482-2490)
  • Hidehiro Kaneko, Toshihisa Anzai, Keisuke Horiuchi, Kokichi Morimoto, Atsushi Anzai, Toshiyuki Nagai, Yasuo Sugano, Yuichiro Maekawa, Hiroshi Itoh, Tsutomu Yoshikawa, Yasunori Okada, Satoshi Ogawa, Keiichi Fukuda
    CIRCULATION JOURNAL 75 (10) 2482 - 2490 1346-9843 2011/10 [Refereed][Not invited]
     
    Background: Tumor necrosis factor (TNF)-alpha, which is released as a soluble form by ectodomain shedding of TNF-alpha converting enzyme (Tace), is known to play a pivotal role in obesity-induced insulin resistance. The role of lace in obesity-induced metabolic disorders was to be clarified in this study. Methods and Results: Transgenic mice with temporal systemic lace deletion (TaceMx1) and their non-transgenic littermates (CON) were fed a standard diet or a high-fat diet (HFD) from 6 weeks of age. The increased body, liver and epididymal adipose tissue (EAT) weights, systolic blood pressure, and fasting glucose and lipid levels and decreased serum adiponectin level 12 weeks after starting a HFD were suppressed by Tace inactivation. A HFD/TaceMx1 showed ameliorated glucose tolerance and insulin sensitivity compared with HFD/CON. Indirect calorimetry showed that energy expenditure and oxidation of both fat and carbohydrate were higher in HFD/TaceMx1 than HFD/CON. Marked hepatosteatosis, increased triglyceride content and TNF-alpha expression in liver, and increased adipocyte size, macrophage infiltration and TNF-alpha and monocyte chemoattractant protein-1 expression in EAT induced by a HFD were attenuated in HFD/TaceMx1. Conclusions: Inactivation of Tace suppressed HFD-induced obesity, insulin resistance, hepatosteatosis and adipose tissue remodeling in association with increased energy expenditure, suggesting an important role of lace in the development of obesity-induced metabolic disorders. (Circ J 2011; 75: 2482-2490)
  • Hidehiro Kaneko, Toshihisa Anzai, Toshiyuki Nagai, Atsushi Anzai, Toshiyuki Takahashi, Yoshinori Mano, Kohkichi Morimoto, Yuichiro Maekawa, Hiroshi Itoh, Tsutomu Yoshikawa, Satoshi Ogawa, Keiichi Fukuda
    CARDIOVASCULAR RESEARCH 91 (3) 546 - 555 0008-6363 2011/08 [Refereed][Not invited]
     
    Aims C-reactive protein (CRP) expression is increased with metabolic alterations. We sought to clarify the effect of CRP on the development of obesity-induced metabolic disorders using human CRP-overexpressing transgenic mice (CRPTG).Methods and results CRPTG and their non-transgenic littermates (CON) were fed a standard diet (STD) or a high-fat diet (HFD) from 6 weeks of age. Oral glucose tolerance and intraperitoneal insulin tolerance tests 12 weeks after starting the diets showed deterioration of glucose tolerance and insulin sensitivity in HFD/CRPTG compared with HFD/CON. Hepatocellular ballooning, oil droplets, and peri-sinusoidal fibrosis were more prominent in HFD/CRPTG than in HFD/CON. In HFD/CRPTG, hepatic triglyceride content was higher and serum adiponectin levels lower than in HFD/CON. Epididymal adipose tissue mRNA expression of mucin-like, hormone receptor-like 1, monocyte chemotactic protein-1, and tumour necrosis factor-a in HFD/CRPTG was up-regulated compared with that in HFD/CON. Immunohistochemical staining of epididymal adipose tissue showed that the number of Mac-3(+) macrophages was higher in HFD/CRPTG than in HFD/CON.Conclusion Human CRP overexpression facilitated the development of insulin resistance and hepatosteatosis with HFD in association with adiponectin down-regulation and enhancement of macrophage infiltration and expression of pro-inflammatory cytokines in epididymal adipose tissue, suggesting its pathogenic role in the development of obesityinduced metabolic disorders.
  • Hidehiro Kaneko, Toshihisa Anzai, Maho Morisawa, Takashi Kohno, Toshiyuki Nagai, Atsushi Anzai, Toshiyuki Takahashi, Masayuki Shimoda, Aya Sasaki, Yuichiro Maekawa, Koichi Yoshimura, Hiroki Aoki, Kazuo Tsubota, Tsutomu Yoshikawa, Yasunori Okada, Satoshi Ogawa, Keiichi Fukuda
    ATHEROSCLEROSIS 217 (2) 350 - 357 0021-9150 2011/08 [Refereed][Not invited]
     
    Objective: We sought to examine the effect of resveratrol (3,4',5-trihydroxy-trans-stilbene), a plant-derived polyphenolic compound, on the development of abdominal aortic aneurysm (AAA). Methods: AAA was induced in mice by periaortic application of CaCl(2). NaCl (0.9%)-applied mice were used as a sham group. Mice were treated with intraperitoneal injection of PBS (Sham/CON, AAA/CON, n = 30 for each) or resveratrol (100 mg/kg/day) (AAA/RSVT, n = 30). Six weeks after the operation, aortic tissue was excised for further examinations. Results: Aortic diameter was enlarged in AAA/CON compared with Sham/CON. Resveratrol treatment reduced the aneurysm size and inflammatory cell infiltration in the aortic wall compared with AAA/CON. Elastica Van Gieson staining showed destruction of the wavy morphology of the elastic lamellae in AAA/CON, while it was preserved in AAA/RSVT. The increased mRNA expression of monocyte chemotactic protein-1, tumor necrosis factor-alpha, intercellular adhesion molecule-1, CD68, vascular endothelial growth factor-A, p47, glutathione peroxidase (GPX) 1 and GPX3 were attenuated by resveratrol treatment (all p < 0.05). Administration of resveratrol decreased protein expression of phospho-p65 in AAA. The increased 8-hydroxy-2'-deoxyguanosine-positive cell count and 4-hydroxy-2-nonenal-positive cell count in AAA were also reduced by resveratrol treatment. Zymographic activity of matrix metalloproteinase (MMP)-9 and MMP-2 was lower in AAA/RSVT compared with AAA/CON (both p < 0.05). Compared with AAA/CON, Mac-2(+) macrophages and CD31(+) vessels in the aortic wall were decreased in AAA/RSVT (both p < 0.05). Conclusion: Treatment with resveratrol in mice prevented the development of CaCl(2)-induced AAA, in association with reduced inflammation, oxidative stress, neoangiogenesis, and extracellular matrix disruption. These findings suggest therapeutic potential of resveratrol for AAA. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
  • Hidehiro Kaneko, Toshihisa Anzai, Toshiyuki Takahashi, Takashi Kohno, Masayuki Shimoda, Aya Sasaki, Hideyuki Shimizu, Toshiyuki Nagai, Yuichiro Maekawa, Koichi Yoshimura, Hiroki Aoki, Tsutomu Yoshikawa, Yasunori Okada, Ryohei Yozu, Satoshi Ogawa, Keiichi Fukuda
    CARDIOVASCULAR RESEARCH 91 (2) 358 - 367 0008-6363 2011/07 [Refereed][Not invited]
     
    Aims Increased angiogenesis, chronic inflammation, and extracellular matrix degradation are the major pathological features of abdominal aortic aneurysm (AAA). We sought to elucidate the role of vascular endothelial growth factor (VEGF)-A, a potent angiogenic and proinflammatory factor, in the development of AAA. Methods and results Human AAA samples showed increased VEGF-A expression, neovascularization, and macrophage infiltration compared with normal aortic walls. AAA was induced in mice by periaortic application of CaCl(2). AAA mice were treated with soluble VEGF-A receptor (sFlt)-1 or phosphate-buffered saline and sacrificed 6 weeks after the operation. Treatment with sFlt-1 resulted in reduced aneurysm size, restored wavy structure of the elastic lamellae, reduced Mac-2(+) monocytes/macrophages, CD3(+) T-lymphocytes, and CD31(+) vessels, and attenuated matrix metalloproteinase (MMP)-2 and 9 activity in periaortic tissue of AAA. Increased aortic mRNA expression of monocyte chemotactic protein-1, tumour necrosis factor-alpha, and intercellular adhesion molecule-1 in AAA was attenuated by sFlt-1 treatment. Conclusion VEGF-A was overexpressed in the aortic wall of human and experimental AAA. Treatment with sFlt-1 inhibited AAA development in mice, in association with reduced neoangiogenesis, infiltration of inflammatory cells, MMP activity, and extracellular matrix degradation. These findings suggest a crucial role of VEGF-A in the development of AAA.
  • Yoshinori Mano, Toshihisa Anzai, Hidehiro Kaneko, Yuji Nagatomo, Toshiyuki Nagai, Atsushi Anzai, Yuichiro Maekawa, Toshiyuki Takahashi, Tomomi Meguro, Tsutomu Yoshikawa, Keiichi Fukuda
    CIRCULATION JOURNAL 75 (7) 1717 - 1727 1346-9843 2011/07 [Refereed][Not invited]
     
    Background: C-reactive protein (CRP) is known to be a pathogenic agent in the cardiovascular system. However, the effect of CRP on heart failure has not been elucidated. The effect of human CRP on cardiac dysfunction induced by diabetes mellitus (DM) using human CRP-overexpressing transgenic mice (CRP-Tg) was examined.Methods and Results: DM was induced in male wild-type mice (Wt/DM) and CRP-Tg (CRP/DM) by an injection of streptozotocin. Non-diabetic wild-type mice (Wt/Con) and CRP-Tg (CRP/Con) served as controls. Echocardiography and hemodynamic measurements 6 weeks after injection showed lower fractional shortening and left ventricular (LV) dP/dt max in CRP/DM compared with Wt/DM. Myocardial mRNA levels of interleukin-6, tumor necrosis factor-a, plasminogen activator inhibitor-1, angiotensin type 1 receptor, angiotensinogen, NADPH oxidase subunits (p47(Phox), gp91(phox)) glutathione peroxidase-3. and connective tissue growth factor were increased in CRP/DM compared with Wt/DM. Nuclear staining of 8-hydroxydeoxyguanosine was also increased in CRP/DM compared with Wt/DM. CRP/DM was associated with increased terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling positive cells and a higher ratio of Bax/Bcl-2 proteins compared with Wt/DM. The extent of cardiac fibrosis assessed by Sirius red staining and immunohistochemical staining for collagen type 1 was significantly increased in CRP/DM compared with Wt/DM.Conclusions: Overexpression of human CRP exacerbates LV dysfunction and remodeling in diabetic cardiomyopathy, possibly through enhancement of the inflammation, renin-angiotensin system, and oxidative stress. (Circ J 2011;75: 1717-1727)
  • Yoshinori Mano, Toshihisa Anzai, Hidehiro Kaneko, Yuji Nagatomo, Toshiyuki Nagai, Atsushi Anzai, Yuichiro Maekawa, Toshiyuki Takahashi, Tomomi Meguro, Tsutomu Yoshikawa, Keiichi Fukuda
    CIRCULATION JOURNAL 75 (7) 1717 - 1727 1346-9843 2011/07 [Refereed][Not invited]
     
    Background: C-reactive protein (CRP) is known to be a pathogenic agent in the cardiovascular system. However, the effect of CRP on heart failure has not been elucidated. The effect of human CRP on cardiac dysfunction induced by diabetes mellitus (DM) using human CRP-overexpressing transgenic mice (CRP-Tg) was examined.Methods and Results: DM was induced in male wild-type mice (Wt/DM) and CRP-Tg (CRP/DM) by an injection of streptozotocin. Non-diabetic wild-type mice (Wt/Con) and CRP-Tg (CRP/Con) served as controls. Echocardiography and hemodynamic measurements 6 weeks after injection showed lower fractional shortening and left ventricular (LV) dP/dt max in CRP/DM compared with Wt/DM. Myocardial mRNA levels of interleukin-6, tumor necrosis factor-a, plasminogen activator inhibitor-1, angiotensin type 1 receptor, angiotensinogen, NADPH oxidase subunits (p47(Phox), gp91(phox)) glutathione peroxidase-3. and connective tissue growth factor were increased in CRP/DM compared with Wt/DM. Nuclear staining of 8-hydroxydeoxyguanosine was also increased in CRP/DM compared with Wt/DM. CRP/DM was associated with increased terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling positive cells and a higher ratio of Bax/Bcl-2 proteins compared with Wt/DM. The extent of cardiac fibrosis assessed by Sirius red staining and immunohistochemical staining for collagen type 1 was significantly increased in CRP/DM compared with Wt/DM.Conclusions: Overexpression of human CRP exacerbates LV dysfunction and remodeling in diabetic cardiomyopathy, possibly through enhancement of the inflammation, renin-angiotensin system, and oxidative stress. (Circ J 2011;75: 1717-1727)
  • Toshiyuki Nagai, Masaru Shibata, Satoru Suzuki, Takashi Matsubara
    Cardiovascular Intervention and Therapeutics 26 (2) 157 - 161 1868-4300 2011/05 [Refereed][Not invited]
     
    Sirolimus-eluting stents (SES) had been implanted in the left anterior descending artery of a 77-year-old male. Three years later, he was admitted for ST elevation myocardial infarction caused by stent thrombosis accompanied with incomplete stent apposition (ISA), and balloon angioplasty had to be performed on him. However, 6 months later, he was admitted for angina. There was progression of ISA and severe stenosis. Considering the allergic reaction to the polymer of the SES, or the risk of future stent thrombosis, coronary artery bypass grafting was selected for the revascularization. One year after the procedure, he felt no symptoms and the bypass graft was patent. A surgical strategy may be considered for recurrence of coronary events accompanied with ISA after stent implantation. © 2010 Japanese Association of Cardiovascular Intervention and Therapeutics.
  • Toshiyuki Nagai, Toshihisa Anzai, Hidehiro Kaneko, Yoshinori Mano, Atsushi Anzai, Yuichiro Maekawa, Toshiyuki Takahashi, Tomomi Meguro, Tsutomu Yoshikawa, Keiichi Fukuda
    HYPERTENSION 57 (2) 208 - 215 0194-911X 2011/02 [Refereed][Not invited]
     
    Serum C-reactive protein (CRP) elevation predicts the development of heart failure in patients with hypertension. CRP activates macrophages and enhances oxidative stress. We hypothesize that CRP itself has a pathogenic role in the development of pressure overload-induced cardiac remodeling. Transgenic mice with human CRP overexpression (CRPtg) and nontransgenic littermates (CON) were subjected to transverse aortic constriction (TAC/CRPtg and TAC/CON) or sham operation (Sham/CRPtg and Sham/CON). One week after operation, in TAC/CRPtg, myocardial mRNA levels of interleukin (IL)-6, CD68, glutathione peroxidase-3 (GPx3), 47-kDa alpha-subunit of nicotinamide adenine dinucleotide phosphate oxidase (p47(phox)), and collagen-I, the number of infiltrating Mac-2-positive macrophages, nuclear localization of phosphorylated NF-kappa B/p65 (p-p65) in cardiomyocytes, nuclear NF-kappa B-DNA-binding activity, and reactive oxygen species (ROS) content were increased compared to those in TAC/CON. Cardiac fibrosis was more prominent in TAC/CRPtg compared to TAC/CON. Four weeks after operation, heart and lung weights, cardiomyocyte cross-sectional area, and the extent of cardiac fibrosis were greater in TAC/CON than in Sham/CON, and these differences were further augmented in TAC/CRPtg compared to TAC/CON. Left ventricular (LV) fractional shortening was less and LV end-diastolic pressure was higher in TAC/CRPtg than in TAC/CON. Myocardial mRNA levels of angiotensin type 1 receptor, atrial natriuretic factor, IL-6, GPx3, p47(phox), collagen-I, and transforming growth factor (TGF)-beta 1, the protein level of TGF-beta 1, and the numbers of Mac-2-positive macrophages and p-p65-positive cells were higher in TAC/CRPtg than in TAC/CON. In conclusion, CRP itself may have a pathogenic role in the development of pressure overload-induced cardiac remodeling, possibly through enhanced inflammation and oxidative stress. (Hypertension. 2011;57:208-215.)
  • Yuichiro Maekawa, Toshiyuki Nagai, Atsushi Anzai
    Inflammation and Allergy - Drug Targets 10 (4) 229 - 235 1871-5281 2011 [Refereed][Not invited]
     
    The pentraxins, C-reactive protein (CRP), serum amyloid P (SAP) and pentraxin3 (PTX3) are useful biomarkers for cardiovascular disease (CVD), particularly ischemic heart disease and heart failure, and are deeply involved in the pathogenesis of CVD linked to inflammation and innate immunity. Circulating elevated pentraxins, especially CRP and PTX3 levels can provide prognostic information for a variety of clinical settings and facilitate the diagnosis of CVD. Changes in these levels over time are also important indicators of pharmacological therapy, and may indicate the mechanisms by which pentraxins directly or indirectly affect the pathophysiology of CVD in an experimental setting. Here, we discuss major relevant findings associated with the clinical implications of CRP and PTX3 and their role in CVD. © 2011 Bentham Science Publishers Ltd.
  • Toshiyuki Takahashi, Toshihisa Anzai, Hidehiro Kaneko, Yoshinori Mano, Atsushi Anzai, Toshiyuki Nagai, Takashi Kohno, Yuichiro Maekawa, Tsutomu Yoshikawa, Keiichi Fukuda, Satoshi Ogawa
    AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY 299 (6) H1795 - H1804 0363-6135 2010/12 [Refereed][Not invited]
     
    Takahashi T, Anzai T, Kaneko H, Mano Y, Anzai A, Nagai T, Kohno T, Maekawa Y, Yoshikawa T, Fukuda K, Ogawa S. Increased C-reactive protein expression exacerbates left ventricular dysfunction and remodeling after myocardial infarction. Am J Physiol Heart Circ Physiol 299: H1795-H1804, 2010. First published September 17, 2010; doi:10.1152/ajpheart.00001.2010.-We previously reported serum C-reactive protein (CRP) elevation after acute myocardial infarction (MI) to be associated with adverse outcomes including cardiac rupture, left ventricular (LV) remodeling, and cardiac death. Experimental studies have indicated that CRP per se has various biological actions including proinflammatory and proapoptotic effects, suggesting a pathogenic role of CRP in the post-MI remodeling process. We tested the hypothesis that increased CRP expression would exacerbate adverse LV remodeling after MI via deleterious effects of CRP. Transgenic mice with human CRP expression (CRP-Tg) and their transgene-negative littermates (control) underwent left coronary artery ligation. There was no apparent difference in phenotypic features between CRP-Tg and control mice before MI. Although mortality and infarct size were similar in the two groups, CRP-Tg mice showed more LV dilation and worse LV function with more prominent cardiomyocyte hypertrophy and fibrosis in the noninfarcted regions after MI than controls. Histological evaluation conducted 1 wk post-MI revealed a higher rate of apoptosis and more macrophage infiltration in the border zones of infarcted hearts from CRP-Tg mice in relation to increased monocyte chemotactic protein (MCP)-1 expression and matrix metalloproteinase (MMP)-9 activity. Increased CRP expression exacerbates LV dysfunction and promotes adverse LV remodeling after MI in mice. The deleterious effect of CRP on post-MI LV remodeling may be associated with increased apoptotic rates, macrophage infiltration, MCP-1 expression, and MMP-9 activity in the border zone.
  • Toshiyuki Nagai, Toshihisa Anzai, Hidehiro Kaneko, Atsushi Anzai, Yoshinori Mano, Yuji Nagatomo, Shun Kohsaka, Yuichiro Maekawa, Akio Kawamura, Tsutomu Yoshikawa, Satoshi Ogawa
    CIRCULATION JOURNAL 74 (9) 1808 - 1814 1346-9843 2010/09 [Refereed][Not invited]
     
    Background: The aim of the present study was to examine the effect of systemic acidosis on the development of malignant ventricular arrhythmias, including sustained ventricular tachycardia and ventricular fibrillation (VT/VF), after reperfused ST-elevation myocardial infarction (STEMI)Methods and Results: A total of 157 consecutive patients with a reperfused STEMI were examined Patients were divided into 2 groups according to the presence or absence of systemic acidosis, defined as arterial blood pH <7 40 on admission Serum creatine kinase and C-reactive protein (CRP) levels were serially measured Systemic acidosis was observed in 53 patients (34%). There was no significant difference in coronary risk factors and arrival time from onset between the 2 groups Estimated glomerular filtration rate (eGFR) on admission was lower in patients with acidosis than in those without (P=0 001) Patients with acidosis had a higher incidence of VT/VF (26% vs 4%, P<0 0001), especially within 48h after STEMI (23% vs 3%, P=0 0002), than those without The peripheral white blood cell count on admission was higher in patients with than in those without acidosis Multivariate analysis showed that systemic acidosis was a strong independent predictor of VT/VF (relative risk=8 79, P=0 002) among variables including prior MI and eGFR <60 ml-min(-1).1 73m(-2).Conclusions: Systemic acidosis was a significant determinant of VT/VF after reperfused STEMI and was associated with elevated serum CRP level. Systemic acidosis and subsequent inflammation after ischemia reperfusion may play an important role in the development of VT/VF (Circ J 2010, 74: 1808-1814)
  • Toshiyuki Nagai, Toshihisa Anzai, Hidehiro Kaneko, Atsushi Anzai, Yoshinori Mano, Yuji Nagatomo, Shun Kohsaka, Yuichiro Maekawa, Akio Kawamura, Tsutomu Yoshikawa, Satoshi Ogawa
    CIRCULATION JOURNAL 74 (9) 1808 - 1814 1346-9843 2010/09 [Refereed][Not invited]
     
    Background: The aim of the present study was to examine the effect of systemic acidosis on the development of malignant ventricular arrhythmias, including sustained ventricular tachycardia and ventricular fibrillation (VT/VF), after reperfused ST-elevation myocardial infarction (STEMI)Methods and Results: A total of 157 consecutive patients with a reperfused STEMI were examined Patients were divided into 2 groups according to the presence or absence of systemic acidosis, defined as arterial blood pH <7 40 on admission Serum creatine kinase and C-reactive protein (CRP) levels were serially measured Systemic acidosis was observed in 53 patients (34%). There was no significant difference in coronary risk factors and arrival time from onset between the 2 groups Estimated glomerular filtration rate (eGFR) on admission was lower in patients with acidosis than in those without (P=0 001) Patients with acidosis had a higher incidence of VT/VF (26% vs 4%, P<0 0001), especially within 48h after STEMI (23% vs 3%, P=0 0002), than those without The peripheral white blood cell count on admission was higher in patients with than in those without acidosis Multivariate analysis showed that systemic acidosis was a strong independent predictor of VT/VF (relative risk=8 79, P=0 002) among variables including prior MI and eGFR <60 ml-min(-1).1 73m(-2).Conclusions: Systemic acidosis was a significant determinant of VT/VF after reperfused STEMI and was associated with elevated serum CRP level. Systemic acidosis and subsequent inflammation after ischemia reperfusion may play an important role in the development of VT/VF (Circ J 2010, 74: 1808-1814)
  • Toshiyuki Nagai, Yoichi Yanagawa, Masaaki Takemoto, Toshihisa Sakamoto, Yoshiaki Okada
    Journal of Trauma 64 (3) E33 - E36 0022-5282 2008 [Refereed][Not invited]

MISC

Books etc

Presentations

  • 心臓サルコイドーシスに対する1次予防ICD～不整脈治療ガイドラインFocus updateを踏まえて～  [Invited]
    永井利幸
    第70回日本不整脈心電学会学術大会 教育講演  2024/07
  • 永井利幸
    第30回日本心臓リハビリテーション学会学術集会 シンポジウム  2024/07
  • 心筋炎診療の最新情報 ～日循ガイドライン改定を踏まえて～  [Invited]
    永井利幸
    日本循環器学会 第131回北海道支部地方会 教育セッション  2024/06
  • 永井利幸
    第88回 日本循環器学会学術集会 プレナリー  2024/03
  • 心筋炎ガイドライン改定と実臨床からみた診療の課題  [Invited]
    永井利幸
    第43回日本画像医学会 シンポジウム  2024/02
  • ステロイド治療の適応と治療抵抗例に対するアプローチ  [Invited]
    永井 利幸
    第43回日本サルコイドーシス/肉芽腫性疾患学会総会 シンポジウム  2023/10
  • エビデンスと実臨床から心臓サルコイドーシス診療を再考する  [Invited]
    永井 利幸
    第27回日本心不全学会 教育講演  2023/10
  • 心不全診療の個別化を考える  [Invited]
    永井利幸
    Sapporo Live Demonstration Course 2023  2023/09
  • 心不全合併心房細動に対する治療戦略Up to date  [Invited]
    永井利幸
    第61回全国自治体病院学会  2023/08
  • 非心臓手術周術期の心筋傷害 ～ガイドラインから対策を考える～  [Invited]
    永井利幸
    日本麻酔科学会 第70回学術集会  2023/06
  • 心臓サルコイドーシスUpdate 2023  [Invited]
    永井利幸
    第9回日本心筋症研究会 シンポジウム  2023/05
  • 2023 年改訂版 心筋炎の診断・治療に関するガイドライン  [Invited]
    永井利幸
    第87回日本循環器学会学術集会 ガイドラインに学ぶ  2023/03
  • Key Points of JCS 2023 Guideline on the Diagnosis and Treatment of Myocarditis: Focus on Chronic Inflammatory Cardiomyopathy  [Invited]
    永井利幸
    第87回日本循環器学会学術集会 Special Session  2023/03
  • 心不全パンデミックに立ち向かう ～理想と現実の狭間で我々が今できること～  [Invited]
    永井利幸
    第175回日本循環器学会東北地方会学術セミナー  2022/12
  • 循環器内科における成人先天性心疾患診療の現状と課題  [Invited]
    永井利幸
    第128回日本循環器学会北海道地方会 北海道ACHDセミナー 2022 Keynote Lecture  2022/11
  • 急性心不全初期マネジメントのコツ ～最近のトレンド～  [Invited]
    永井利幸
    第296回日本内科学会北海道地方会 教育セミナー  2022/11
  • Clinical Features and Outcomes of Heart Failure with Preserved Ejection Fraction in Japan  [Invited]
    永井利幸
    第26回⽇本⼼不全学会学術集会 ジョイントシンポジウム （日本・欧州・米国心不全学会合同シンポジウム）  2022/10
  • 心臓サルコイドーシス診療の現状と課題  [Invited]
    永井利幸
    第26回⽇本⼼不全学会学術集会 シンポジウム  2022/10
  • 永井利幸
    第42回日本サルコイドーシス/肉芽腫性疾患学会総会 シンポジウム  2022/10
  • 永井利幸
    第42回日本サルコイドーシス/肉芽腫性疾患学会総会 シンポジウム  2022/10
  • 永井利幸
    第70回日本心臓病学会学術集会 シンポジウム  2022/09
  • Post ISCHEMIA時代の心筋虚血評価における心筋シンチの位置づけ  [Invited]
    永井利幸
    第70回日本心臓病学会学術集会 シンポジウム  2022/09
  • 二次性心筋症診断の最新情報  [Invited]
    永井利幸
    日本内科学会 第295回北海道地方会 教育セミナー  2022/07
  • 心不全薬物治療を整理する ～各薬剤の位置づけ～  [Invited]
    永井利幸
    第28回日本心臓リハビリテーション学会学術集会 ランチョンセミナー  2022/06
  • 各国ガイドラインの変遷から見る心筋炎診療の課題と展望  [Invited]
    永井利幸
    第8回日本心筋症研究会 シンポジウム  2022/05
  • 永井利幸
    Japanese Circulation Society Chairman’s Special Program  2022/03
  • 永井利幸
    Japanese Circulation Society Topic  2022/03
  • 札幌市における急性冠症候群の診療実態調査：札幌市ACSネットワーク  [Invited]
    永井利幸
    第35回日本冠疾患学会学術集会 シンポジウム  2021/12
  • 心臓サルコイドーシスUp to date 2021  [Invited]
    永井利幸
    日本循環器学会 第126回北海道支部地方会 教育セッション  2021/11
  • 症例からみる心臓限局性サルコイドーシス～心内膜心筋生検の意義～  [Invited]
    永井利幸
    第41回日本サルコイドーシス/肉芽腫性疾患学会総会 シンポジウム  2021/10
  • 最先端テクノロジーを駆使した本邦心不全患者におけるPrecision Medicineプラットフォーム構築
    永井利幸
    第69回日本心臓病学会学術集会 バイエル循環器病研究助成 第27回研究発表会  2021/09
  • 永井利幸
    第7回日本心筋症研究会 シンポジウム  2021/04
  • Toshiyuki Nagai
    Japanese Circulation Society Meet the Expert  2021/03
  • Toshiyuki Nagai
    Japanese Circulation Society Topic  2021/03
  • Clinical Phenotypes of Japanese Heart Failure Patients with Preserved Ejection Fraction  [Invited]
    永井利幸
    Japanese Circulation Society Chairman’s Special Program  2021/03
  • 心不全薬物治療の現状と将来展望  [Invited]
    永井利幸
    日本心臓リハビリテーション学会 第6回近畿支部地方会 共催セミナー  2021/02
  • 第51回日本心血管インターベンション治療学会北海道地方会会長  [Invited]
    永井利幸
    2020/12
  • 心臓サルコイドーシスに合併する心不全と治療薬の新潮流  [Invited]
    永井利幸
    第40回日本サルコイドーシス/肉芽腫性疾患学会総会 共催セミナー  2020/10
  • 心臓サルコイドーシス診療の現状と課題  [Invited]
    永井利幸
    第40回日本サルコイドーシス/肉芽腫性疾患学会総会 シンポジウム  2020/10
  • 心臓サルコイドーシスの心筋病理組織所見を如何に実臨床に役立てるか  [Invited]
    永井利幸
    第40回日本サルコイドーシス/肉芽腫性疾患学会総会 シンポジウム  2020/10
  • 疫学・画像・病理学的解析を駆使した心臓サルコイドーシスの多面的臨床研究  [Invited]
    永井利幸
    第40回日本サルコイドーシス/肉芽腫性疾患学会総会 「千葉保之・本間日臣記念賞」受賞講演  2020/10
  • 高齢心不全患者における栄養状態評価の重要性と栄養障害に対する多職種介入.  [Invited]
    永井利幸
    第24回日本心不全学会学術集会 シンポジウム  2020/10
  • 心不全メガトライアルから読み解くアンジオテンシン受容体-ネプリライシン阻害薬の適応と効果  [Invited]
    永井利幸
    第24回日本心不全学会 教育講演  2020/10
  • High-density lipoprotein cholesterol does not predict future cardiovascular events in patients treated with statins for secondary prevention: an observation from the REAL-CAD study.  [Not invited]
    Toshiyuki Nagai
    European Society of Cardiology Congress 2020 Deep Dive in Risk Factors and Prevention: Abstract Oral Presentation  2020/09
  • Toshiyuki Nagai
    The 84th Annual Scientific Meeting of the Japanese Circulation Society: Symposium  2020/08
  • Toshiyuki Nagai
    The 84th Annual Scientific Meeting of the Japanese Circulation Society: Topic  2020/07
  • Toshiyuki Nagai
    Japanese Circulation Society AHA-JCS Joint Symposium  2020/07
  • 高出血リスク症例に対するPCIを再考する  [Invited]
    永井利幸
    岩手リアルワールドライブ2019 ランチョンセミナー  2019/12
  • How to Handle Rhythm Disturbances and Sudden Cardiac Death in Cardiac Sarcoidosis  [Invited]
    Toshiyuki Nagai
    Korean Society of Cardiology, 3rd Cardiac ASH Conference 2019  2019/11
  • Guidelines for the Diagnosis of Cardiac Sarcoidosis. Sarcoidosis: Diagnostic Issues  [Invited]
    Toshiyuki Nagai
    Korean Society of Cardiology, 3rd Cardiac ASH Conference 2019  2019/11
  • 心臓サルコイドーシスにおける免疫抑制療法と治療効果判定の実際  [Invited]
    永井利幸
    第23回日本心不全学会 教育講演  2019/10
  • JASPER研究から見えてきた本邦HFpEF患者の特徴と今後の展望  [Invited]
    永井利幸
    第23回日本心不全学会学術集会 シンポジウム  2019/10
  • 心臓サルコイドーシスにおける免疫応答機構と病理組織診断への応用  [Invited]
    永井利幸
    第5回日本心筋症研究会 シンポジウム  2019/07
  • Transcultural lessons in managements and outcomes for hospitalized heart failure - Insight from national claim data across Asian and Western countries -  [Not invited]
    永井利幸
    第83回日本循環器学会学術集会 シンポジウム  2019/03
  • 心臓サルコイドーシス診療におけるFDG-PETによる活動性評価をガイドとした免疫抑制療法戦略の限界  [Invited]
    永井利幸
    第38回日本サルコイドーシス/肉芽腫性疾患学会総会 シンポジウム  2018/11
  • Validation of mortality prediction models derived from Western countries on Japanese hospitalized heart failure cohorts with future perspectives  [Invited]
    Toshiyuki Nagai
    9th Asian Pacific Congress of Heart Failure: Symposium  2018/10
  • 非肉芽腫組織における免疫応答に着目した新規心臓サルコイドーシス組織診断法に関する検討  [Not invited]
    永井利幸
    第66回日本心臓病学会学術集会 シンポジウム  2018/09
  • Effect of intravenous carperitide versus nitrates as first-line vasodilators on in-hospital outcomes in hospitalized patients with acute heart failure - Insight from a nationwide claim-based database -  [Not invited]
    Toshiyuki Nagai
    European Society of Cardiology Congress 2018: Advanced in Science: Abstract Oral Presentation  2018/08
  • HFpEFの診断と最新治療戦略  [Invited]
    永井利幸
    日本心臓病学会教育セミナー（アドバンストコース）  2017/02
  • The Importance of Assessing Nutritional Status in Patients with Acute Heart Failure  [Invited]
    Toshiyuki Nagai
    5th Annual World Congress of Food and Nutrition: Symposium  2016/11
  • 心不全の心腎貧血連関における内因性エリスロポエチンの予後的意義  [Not invited]
    永井利幸
    第20回日本心不全学会学術集会 シンポジウム  2016/10
  • 血漿BNPによるHFpEF症例の予後リスク層別化と治療戦略への応用  [Invited]
    永井利幸
    第20回日本心不全学会学術集会 パネルディスカッション  2016/10
  • 心臓サルコイドーシスにおけるステロイド療法の現状と今後の課題  [Invited]
    永井利幸
    第64回日本心臓病学会学術集会 日本心臓核医学学会ジョイントシンポジウム  2016/09
  • Diagnosis and Treatment of Cardiac Sarcoidosis Up To Date  [Invited]
    永井利幸
    第63回日本不整脈心電学会学術集会 シンポジウム  2016/07
  • 心臓サルコイドーシスにおけるステロイド治療～開始と中止の至適タイミングをどのように考えるべきか～  [Invited]
    永井利幸
    第2回日本心筋症研究会 シンポジウム  2016/05
  • 急性心不全における虚血性心筋症の特徴と長期予後規定因子に関する検討～非虚血性心筋症との比較から～  [Not invited]
    永井利幸
    第29回日本冠疾患学会学術集会 内科シンポジウム  2015/11
  • Remaining Non-pharmacological Approaches for Acute Heart Failure  [Invited]
    永井利幸
    第79回日本循環器学会学術集会 トピック  2015/04
  • The Importance of Assessing Nutritional Status in Patients with Acute Heart Failure  [Not invited]
    永井利幸
    第79回日本循環器学会学術集会 シンポジウム  2015/04
  • Decreased Myocardial Dendritic Cells is Associated with Impaired Reparative Fibrosis and Development of Cardiac Rupture after Myocardial Infarction in Humans  [Not invited]
    Toshiyuki Nagai
    European Society of Cardiology Congress 2014: Abstract Oral Presentation  2014/09
  • 長期予後を見据えた急性非代償性心不全症例に対する早期栄養介入の必要性  [Not invited]
    永井利幸
    第62回日本心臓病学会学術集会 シンポジウム  2014/09
  • 病棟で役に立つ循環器身体所見と心電図判読のコツ  [Invited]
    永井利幸
    日本循環器看護学会教育セミナー  2013/10
  • 心臓サルコイドーシス診断時のImaging modalityによる活動性の評価はステロイド治療開始の基準となりうるか  [Invited]
    永井利幸
    第61回日本心臓病学会学術集会 ビジュアルワークショップ  2013/09
  • 心臓外サルコイドーシス症例の心臓病変早期検出における心臓ＭＲＩの有用性  [Not invited]
    永井利幸
    第60回日本心臓病学会学術集会 ビジュアルワークショップ  2012/09

Association Memberships

  • 日本高血圧学会   European Society of Cardiology   American College of Cardiology   Japan Society of Sarcoidosis and Other Granulomatous Disorders   Japan Transcatheter Valve Therapies   THE JAPANESE SOCIETY OF INTENSIVE CARE MEDICINE   JAPANESE ASSOCIATION OF CARDIOVASCULAR INTERVENTION AND THERAPEUTICS   Japanese College of Cardiology   JAPANESE HEART FAILURE SOCIETY   The Japanese Circulation Society   THE JAPANESE SOCIETY OF INTERNAL MEDICINE   

Research Projects

Social Contribution

  • 心疾患の治療と予防
    Date (from-to) : 2023/02/14-2023/02/14
    Role : Lecturer
    Sponser, Organizer, Publisher  : 共催：北海道 日本脳卒中協会（北海道支部） 日本循環器協会 協和キリン株式会社
    Event, Program, Title : 第 2 回循環器病住民講演会

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