2022/11/29 更新

写真a

イシハラ シロウ
石原 嗣郎
ISHIHARA Shiro
所属
医歯学総合病院 循環器内科 助教
職名
助教
外部リンク

学位

  • 学士 ( 2001年4月   琉球大学 )

研究分野

  • ライフサイエンス / 循環器内科学

経歴(researchmap)

  • 新潟大学大学院医歯学総合研究科   循環器内科学   専任助教

    2022年1月 - 現在

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  • 日本医科大学武蔵小杉病院   循環器内科   循環器内科医長・内科(総合)医長兼任

    2020年4月 - 2021年12月

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  • 日本医科大学武蔵小杉病院   循環器内科   医長

    2019年4月 - 2021年12月

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  • 日本医科大学武蔵小杉病院   循環器内科

    2014年5月 - 2021年12月

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  • Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France   Biomarkers and Heart Diseases, UMR-942

    2013年2月 - 2014年4月

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  • 新日鐵八幡記念病院   循環器内科

    2007年5月 - 2013年2月

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  • 新日鐵八幡記念病院   救急・集中治療部

    2005年5月 - 2007年4月

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  • 沖縄県立那覇病院   循環器内科

    2004年5月 - 2005年4月

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  • 沖縄県立那覇病院   救急部

    2003年5月 - 2004年4月

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  • 新日鐵八幡記念病院   研修医

    2002年5月 - 2003年4月

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  • 琉球大学医学部付属病院   第3内科   研修医

    2001年5月 - 2002年4月

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  • 琉球大学医学部医学科

    1994年5月 - 2001年4月

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経歴

  • 新潟大学   医歯学総合病院 循環器内科   助教

    2022年1月 - 現在

所属学協会

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委員歴

  • 日本臨床救急医学会   PEMECガイドブック改訂に関する編集委員会 委員  

    2022年 - 現在   

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  • 日本循環器学会   メディカルコントロール協議会 委員  

    2022年 - 現在   

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  • 日本臨床救急医学会   循環器救急疾患の病院前救護検討小委員会 委員長  

    2021年 - 現在   

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  • 日本臨床救急医学会   教育研修委員会 委員  

    2021年 - 現在   

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  • 日本循環器学会   集中・救急医療部会救急医療制度検討会 委員  

    2021年 - 現在   

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  • 日本心不全学会   代議員  

    2018年 - 現在   

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  • 日本心不全ネットワーク   理事  

    2017年 - 現在   

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  • European society of cardiology   HOT (Heart failure specialist Of Tomorrow) 元日本代表  

    2014年 - 2018年   

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論文

  • Paradigm shift in heart failure treatment: are cardiologists ready to use gliflozins? 国際誌

    Michele Correale, Renata Petroni, Stefano Coiro, Elena-Laura Antohi, Francesco Monitillo, Marta Leone, Marco Triggiani, Shiro Ishihara, Hans-Dirk Dungen, Chaudhry M S Sarwar, Maurizio Memo, Hani N Sabbah, Marco Metra, Javed Butler, Savina Nodari

    Heart failure reviews   27 ( 4 )   1147 - 1163   2022年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Despite recent advances in chronic heart failure (HF) therapy, the prognosis of HF patients remains poor, with high rates of HF rehospitalizations and death in the early months after discharge. This emphasizes the need for incorporating novel HF drugs, beyond the current approach (that of modulating the neurohumoral response). Recently, new antidiabetic oral medications (sodium-glucose cotransporter 2 inhibitors (SGLT2i)) have been shown to improve prognosis in diabetic patients with previous cardiovascular (CV) events or high CV risk profile. Data from DAPA-HF study showed that dapaglifozin is associated with a significant reduction in mortality and HF hospitalization as compared with placebo regardless of diabetes status. Recently, results from EMPEROR-Reduced HF trial were consistent with DAPA-HF trial findings, showing significant beneficial effect associated with empagliflozin use in a high-risk HF population with markedly reduced ejection fraction. Results from the HF with preserved ejection fraction trials using these same agents are eagerly awaited. This review summarizes the evidence for the use of gliflozins in HF treatment.

    DOI: 10.1007/s10741-021-10107-8

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  • Haemodynamic effects of the nitroxyl donor cimlanod (BMS-986231) in chronic heart failure: a randomized trial. 国際誌

    Ninian N Lang, Faheem A Ahmad, John G Cleland, Christopher M O'Connor, John R Teerlink, Adriaan A Voors, Jorg Taubel, Anke R Hodes, Mohamed Anwar, Ravi Karra, Yasushi Sakata, Shiro Ishihara, Roxy Senior, Abhishek Khemka, Narayana G Prasad, Mary M DeSouza, Dietmar Seiffert, June Y Ye, Paul D Kessler, Maria Borentain, Scott D Solomon, G Michael Felker, John J V McMurray

    European journal of heart failure   23 ( 7 )   1147 - 1155   2021年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on cardiac function in patients with chronic heart failure with reduced ejection fraction (HFrEF). METHODS AND RESULTS: In a randomized, multicentre, double-blind, crossover trial, 45 patients with stable HFrEF were given a 5 h intravenous infusion of cimlanod, NTG, or placebo on separate days. Echocardiograms were done at the start and end of each infusion period and read in a core laboratory. The primary endpoint was stroke volume index derived from the left ventricular outflow tract at the end of each infusion period. Stroke volume index with placebo was 30 ± 7 mL/m2 and was lower with cimlanod (29 ± 9 mL/m2 ; P = 0.03) and NTG (28 ± 8 mL/m2 ; P = 0.02). Transmitral E-wave Doppler velocity on cimlanod or NTG was lower than on placebo and, consequently, E/e' (P = 0.006) and E/A ratio (P = 0.003) were also lower. NTG had similar effects to cimlanod on these measurements. Blood pressure reduction was similar with cimlanod and NTG and greater than with placebo. CONCLUSION: In patients with chronic HFrEF, the haemodynamic effects of cimlanod and NTG are similar. The effects of cimlanod may be explained by venodilatation and preload reduction without additional inotropic or lusitropic effects. Ongoing trials of cimlanod will further define its potential role in the treatment of heart failure.

    DOI: 10.1002/ejhf.2138

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  • Temporal trends in mortality and readmission after acute heart failure: a systematic review and meta-regression in the past four decades. 国際誌

    Antoine Kimmoun, Koji Takagi, Emmanuel Gall, Shiro Ishihara, Pierre Hammoum, Nathan El Bèze, Alexandre Bourgeois, Guillaume Chassard, Hugo Pegorer-Sfes, Etienne Gayat, Alain C Solal, Alexa Hollinger, Thomas Merkling, Alexandre Mebazaa

    European journal of heart failure   23 ( 3 )   420 - 431   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: Acute heart failure (AHF) is frequent and life-threatening disease. However, innovative AHF therapies have remained limited, and care is based on experts' opinion. Temporal trends and benefits of long-term oral cardiovascular medications on AHF outcomes remain uncertain. METHODS AND RESULTS: This study is registered with PROSPERO (CRD42018099885). A systematic review ranging from 1980 to 2017, searched AHF studies with more than 100 patients that reported death and/or readmission. Primary outcomes were temporal trends, assessed by meta-regression, for 30-day or 1-year all-cause death and/or readmission rates. Secondary outcomes were temporal trends of oral cardiovascular therapies and their influence on primary outcomes. Among the 45 143 studies screened, 285 were included, representing 15 million AHFs. In the past decades, though mortality and readmission remain high, there was a decline in 30-day all-cause death [odds ratio (OR) for a 10-year increment: 0.74, 95% confidence interval (CI) 0.61-0.91; P = 0.004] that persisted at 1 year (OR 0.86, 95% CI 0.77-0.96; P = 0.007), while 30-day and 1-year all-cause readmission rate remained roughly unchanged. Trends of primary outcomes were linear and did not differ among continents. Decline in 1-year all-cause death rate correlated with high proportions of oral or beta-blockers, especially when combined with oral renin-angiotensin-aldosterone system inhibitors, but not with diuretics while trends in readmission remained unchanged with these therapies. CONCLUSIONS: Although AHF outcomes remain poor, the present study revealed global favourable trends of survival after AHF episodes probably associated with greater use of oral neurohormonal antagonists. The present study urges to implement the combination of oral renin-angiotensin-aldosterone system inhibitors and beta-blockers in patients at risk of AHF.

    DOI: 10.1002/ejhf.2103

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  • Differences in pharmacological property between combined therapy of the vasopressin V2-receptor antagonist tolvaptan plus furosemide and monotherapy of furosemide in patients with hospitalized heart failure. 国際誌

    Koji Takagi, Naoki Sato, Shiro Ishihara, Hayano Iha, Noriyuki Kobayashi, Yusuke Ito, Tsuyoshi Nohara, Satoru Ohkuma, Tatsuya Mitsuishi, Atsushi Ishizuka, Shota Shigihara, Michiko Sone, Kenji Nakama, Hideo Tokuyama, Toshiya Omote, Arifumi Kikuchi, Shunichi Nakamura, Eisei Yamamoto, Masahiro Ishikawa, Kenichi Amitani, Naoto Takahashi, Yuji Maruyama, Hajime Imura, Wataru Shimizu

    Journal of cardiology   76 ( 5 )   499 - 505   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Tolvaptan has been shown to improve congestion in heart failure patients. The purpose of this study was to evaluate the pharmacology and clinical efficacy of combined tolvaptan and furosemide therapy. METHODS: This study included 40 patients with systemic volume overload who were hospitalized for heart failure. Patients who showed no improvement in the condition after receiving 20 mg intravenous furosemide were included and were randomly selected to receive tolvaptan as an add-on to furosemide or to receive an increased dose of furosemide. We evaluated the bioelectrical impedance analyzer parameters, the parameters of the inferior vena cava using echocardiography, vital signs, body weight, urine output, and laboratory data for 5 days. RESULTS: In the changes from baseline between intracellular water volume (ICW) and extracellular water volume (ECW) after additional use of tolvaptan or furosemide from Day 1 to Day 5, there were no significant differences observed between ICW and ECW over 5 days in the tolvaptan + furosemide group, although differences were found in the furosemide group from Day 2 onward. Changes in the respiratory collapse of inferior vena cava increased significantly, and systolic blood pressure decreased significantly only in the furosemide group. CONCLUSIONS: The present study clearly demonstrates that combined therapy with tolvaptan and furosemide removed excess ICW and ECW to an equal extent, while furosemide alone primarily removed ECW, including intravascular water.

    DOI: 10.1016/j.jjcc.2020.05.012

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  • Clinical significance of arterial stiffness as a factor for hospitalization of heart failure with preserved left ventricular ejection fraction: a retrospective matched case-control study. 国際誌

    Koji Takagi, Shiro Ishihara, Nakama Kenji, Hayano Iha, Noriyuki Kobayashi, Yusuke Ito, Tsuyoshi Nohara, Satoru Ohkuma, Tatsuya Mitsuishi, Atsushi Ishizuka, Shota Shigihara, Michiko Sone, Hideo Tokuyama, Toshiya Omote, Arifumi Kikuchi, Shunichi Nakamura, Eisei Yamamoto, Masahiro Ishikawa, Kenichi Amitani, Naoto Takahashi, Yuji Maruyama, Hajime Imura, Naoki Sato, Wataru Shimizu

    Journal of cardiology   76 ( 2 )   171 - 176   2020年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Previous studies have been conducted to identify characteristics of patients with heart failure with preserved ejection fraction (HFpEF), but the risk factors of HFpEF remain unclear. We investigated the associations between arterial stiffness and the risk of hospitalization for HFpEF patients. METHODS: For the case group, we enrolled patients with preserved EF who had been hospitalized for HF from April 2013 to March 2015 and examined the cardio-ankle vascular index (CAVI). For the control group, we enrolled outpatients with preserved EF and with hypertension, diabetes mellitus, dyslipidemia, and/or coronary artery disease but who did not present with HF symptoms and had never been diagnosed or treated for HF during the same period. The control group matched with the case group for age and sex. The association between hospitalized HFpEF and clinical variables was analyzed using conditional logistic regression models. RESULTS: The CAVI value was significantly higher in patients with hospitalized HFpEF compared with patients with the control [10.4 (9.8-11.0) vs. 9.2 (8.1-10.0), p < 0.001). On the multivariate conditional logistic regression analysis, high CAVI (OR 6.76, 95% CI 2.28-20.10, p < 0.001) and anemia (OR 3.91, 95% CI 1.47-10.40, p = 0.006) were independently associated with hospitalization of HFpEF patients. CONCLUSIONS: The present study has demonstrated that the high value of CAVI was independently associated with the hospitalization of HFpEF patients.

    DOI: 10.1016/j.jjcc.2020.02.013

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  • One-Year Prognosis of Kidney Injury at Discharge From the ICU: A Multicenter Observational Study. 国際誌

    Matthieu Legrand, Alexa Hollinger, Antoine Vieillard-Baron, François Dépret, Alain Cariou, Nicolas Deye, Marie-Céline Fournier, Samir Jaber, Charles Damoisel, Qin Lu, Xavier Monnet, Isabelle Rennuit, Michael Darmon, Lara Zafrani, Marc Leone, Bertrand Guidet, Diane Friedman, Romain Sonneville, Philippe Montravers, Sébastien Pili-Floury, Jean-Yves Lefrant, Jacques Duranteau, Pierre-François Laterre, Nicolas Brechot, Haikel Oueslati, Bernard Cholley, Jean-Marie Launay, Shiro Ishihara, Naoki Sato, Alexandre Mebazaa, Etienne Gayat

    Critical care medicine   47 ( 12 )   e953-e961   2019年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: The association between outcome and kidney injury detected at discharge from the ICU using different biomarkers remains unknown. The objective was to evaluate the association between 1-year survival and kidney injury at ICU discharge. DESIGN: Ancillary investigation of a prospective observational study. SETTING: Twenty-one ICUs with 1-year follow-up. PATIENTS: Critically ill patients receiving mechanical ventilation and/or hemodynamic support for at least 24 hours were included. INTERVENTIONS: Serum creatinine, plasma Cystatin C, plasma neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, plasma Proenkephalin A 119-159, and estimated glomerular filtration rate (on serum creatinine and plasma Cystatin C) were measured at ICU discharge among ICU survivors. MEASUREMENTS AND MAIN RESULTS: The association between kidney biomarkers at discharge and mortality was estimated using logistic model with and without adjustment for prognostic factors previously identified in this cohort. Subgroup analyses were performed in patients with discharge serum creatinine less than 1.5-fold baseline at ICU discharge. Among 1,207 ICU survivors included, 231 died during the year following ICU discharge (19.2%). Estimated glomerular filtration rate was significantly lower and kidney injury biomarkers higher at discharge in nonsurvivors. The association between biomarker levels or estimated glomerular filtration rate and mortality remained after adjustment to potential cofounding factors influencing outcome. In patients with low serum creatinine at ICU discharge, 25-47% of patients were classified as subclinical kidney injury depending on the biomarker. The association between kidney biomarkers and mortality remained and mortality was higher than patients without subclinical kidney injury. The majority of patients who developed acute kidney injury during ICU stay had elevated biomarkers of kidney injury at discharge even with apparent recovery based on serum creatinine (i.e., subclinical acute kidney disease). CONCLUSIONS: Elevated kidney biomarkers measured at ICU discharge are associated with poor 1-year outcome, including in patients with low serum creatinine at ICU discharge.

    DOI: 10.1097/CCM.0000000000004010

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  • JCS 2017/JHFS 2017 Guideline on Diagnosis and Treatment of Acute and Chronic Heart Failure - Digest Version.

    Hiroyuki Tsutsui, Mitsuaki Isobe, Hiroshi Ito, Hiroshi Ito, Ken Okumura, Minoru Ono, Masafumi Kitakaze, Koichiro Kinugawa, Yasuki Kihara, Yoichi Goto, Issei Komuro, Yoshikatsu Saiki, Yoshihiko Saito, Yasushi Sakata, Naoki Sato, Yoshiki Sawa, Akira Shiose, Wataru Shimizu, Hiroaki Shimokawa, Yoshihiko Seino, Koichi Node, Taiki Higo, Atsushi Hirayama, Miyuki Makaya, Tohru Masuyama, Toyoaki Murohara, Shin-Ichi Momomura, Masafumi Yano, Kenji Yamazaki, Kazuhiro Yamamoto, Tsutomu Yoshikawa, Michihiro Yoshimura, Masatoshi Akiyama, Toshihisa Anzai, Shiro Ishihara, Takayuki Inomata, Teruhiko Imamura, Yu-Ki Iwasaki, Tomohito Ohtani, Katsuya Onishi, Takatoshi Kasai, Mahoto Kato, Makoto Kawai, Yoshiharu Kinugasa, Shintaro Kinugawa, Toru Kuratani, Shigeki Kobayashi, Yasuhiko Sakata, Atsushi Tanaka, Koichi Toda, Takashi Noda, Kotaro Nochioka, Masaru Hatano, Takayuki Hidaka, Takeo Fujino, Shigeru Makita, Osamu Yamaguchi, Uichi Ikeda, Takeshi Kimura, Shun Kohsaka, Masami Kosuge, Masakazu Yamagishi, Akira Yamashina

    Circulation journal : official journal of the Japanese Circulation Society   83 ( 10 )   2084 - 2184   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1253/circj.CJ-19-0342

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  • Prolonged corrected QT interval is associated with short-term and long-term mortality in critically ill patients: results from the FROG-ICU study. 国際誌

    Tuija Javanainen, Shiro Ishihara, Etienne Gayat, Beny Charbit, Raija Jurkko, Raphaël Cinotti, Alexandre Mebazaa

    Intensive care medicine   45 ( 5 )   746 - 748   2019年5月

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  • New-onset atrial fibrillation in critically ill patients and its association with mortality: A report from the FROG-ICU study. 国際誌

    Mattia Arrigo, Shiro Ishihara, Elodie Feliot, Alain Rudiger, Nicolas Deye, Alain Cariou, Bertrand Guidet, Samir Jaber, Marc Leone, Matthieu Resche-Rigon, Antoine Vieillard Baron, Matthieu Legrand, Etienne Gayat, Alexandre Mebazaa

    International journal of cardiology   266   95 - 99   2018年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Atrial fibrillation (AFib) is associated with adverse outcome in critical illness, but whether this effect is independent from other risk factors remains uncertain. New-onset AFib during critical illness may be independently associated with increased in-hospital and long-term risk of death. METHODS: FROG-ICU was a prospective, observational, multi-centre cohort study designed to investigate the outcome of critically ill patients. Inclusion criteria were invasive mechanical ventilation and/or treatment with a positive inotropic agent for >24 h. Heart rhythm was assessed at inclusion and during ICU stay with digital ECG recordings. Among patients who had AFib during ICU stay, new-onset and recurrent AFib were diagnosed in patients without and with previous history of AFib, respectively. Primary endpoint was in-hospital mortality; secondary endpoint was 1-year mortality among ICU survivors. RESULTS: The study included 1841 critically ill patients. During ICU stay, AFib occurred in 343 patients (19%). New-onset AFib (n = 212) had higher in-hospital mortality compared to no AFib (47 vs. 23%, P < 0.001) or recurrent AFib (34%, P = 0.032). New-onset AFib showed increased risk of in-hospital death after multivariable adjustment compared to no AFib (OR 1.6, P = 0.003) or recurrent AFib (OR 1.8, P = 0.02). Among the 1464 ICU-survivors, new-onset AFib during ICU stay showed higher post-ICU risk of death compared to no AFib (HR 2.2, P < 0.001). After multivariable adjustment, new-onset AFib showed higher post-ICU risk of death compared to no AFib (HR 1.6, P = 0.03). CONCLUSION: New-onset AFib is independently associated with in-hospital and post-ICU risk of death in critically ill patients.

    DOI: 10.1016/j.ijcard.2018.03.051

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  • A new educational program in heart failure drug development: the Brescia international master program. 国際誌

    Hans-Dirk Dungen, Renata Petroni, Michele Correale, Stefano Coiro, Francesco Monitillo, Marco Triggiani, Marta Leone, Elena-Laura Antohi, Shiro Ishihara, Chaudhry M S Sarwar, Hani N Sabbah, Maurizio Memo, Marco Metra, Javed Butler, Savina Nodari, Mihai Gheorghiade

    Journal of cardiovascular medicine (Hagerstown, Md.)   19 ( 8 )   411 - 421   2018年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    : Despite recent advances in chronic heart failure treatment, prognosis of acute heart failure patients remains poor with a heart failure rehospitalization rate or death reaching approximately 25% during the first 6 months after discharge. In addition, about half of these patients have preserved ejection fraction for which there are no evidence-based therapies. Disappointing results from heart failure clinical trials over the past 20 years emphasize the need for developing novel approaches and pathways for testing new heart failure drugs and devices. Indeed, many trials are being conducted without matching the mechanism and action of the drug with the clinical event. The implementation of these novel approaches should be coupled with the training of a new generation of heart failure physicians and scientists in the art and science of clinical trials. Currently, drug development is led by opinion leaders and experts who, despite their huge personal experience, were never trained systematically on drug development. The aim of this article is to propose a training program of 'drug development in Heart Failure'. A physician attending this course would have to be trained with a major emphasis on heart failure pathophysiology to better match mechanisms of death and rehospitalization with mechanism of action of the drug. Applicants will have to prove their qualifications and special interest in heart failure drug development before enrollment. This article should serve as a roadmap on how to apply emerging general principles in an innovative drug-development-in-heart-failure-process as well as the introduction of a new educational and mentorship program focusing on younger generations of researchers.

    DOI: 10.2459/JCM.0000000000000669

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  • East Asia may have a better 1-year survival following an acute heart failure episode compared with Europe: results from an international observational cohort. 国際誌

    Eiichi Akiyama, Lucas N L Van Aelst, Mattia Arrigo, Johan Lassus, Òscar Miró, Jelena Čelutkienė, Dong-Ju Choi, Alain Cohen-Solal, Shiro Ishihara, Katsuya Kajimoto, Said Laribi, Aldo Pietro Maggioni, Justina Motiejunaite, Christian Mueller, Jiri Parenica, Jin Joo Park, Naoki Sato, Jindrich Spinar, Jian Zhang, Yuhui Zhang, Kazuo Kimura, Kouichi Tamura, Etienne Gayat, Alexandre Mebazaa

    European journal of heart failure   20 ( 6 )   1071 - 1075   2018年6月

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    記述言語:英語  

    DOI: 10.1002/ejhf.1152

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  • Effects of tolvaptan on urine output in hospitalized heart failure patients with hypoalbuminemia or proteinuria.

    Koji Takagi, Naoki Sato, Shiro Ishihara, Michiko Sone, Hideo Tokuyama, Kenji Nakama, Toshiya Omote, Arifumi Kikuchi, Masahiro Ishikawa, Kenichi Amitani, Naoto Takahashi, Yuji Maruyama, Hajime Imura, Wataru Shimizu

    Heart and vessels   33 ( 4 )   413 - 420   2018年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Hypoalbuminemia is an independent prognostic factor in hospitalization for heart failure (HHF). Hypoalbuminemia or proteinuria is related to resistance to loop diuretics. Tolvaptan is an oral non-peptide, competitive antagonist of vasopressin receptor-2. It has been used for the treatment of volume overload in HHF patients in several Asian countries. Several studies have demonstrated marked improvement in congestion in HHF patients. However, whether tolvaptan is useful for HHF patients with hypoalbuminemia or proteinuria (both of which are related to resistance to loop diuretics) has not been clarified. We examined the diuretic response to tolvaptan in HHF patients with hypoalbuminemia or proteinuria. We defined hypoalbuminemia as a serum level of albumin < 2.6 g/dl. Fifty-one HHF patients who received additional tolvaptan upon therapies with loop diuretics were divided into the hypoalbuminemia group (n = 24) or control group (n = 27). The changes in urine output per day were not different between the two groups [610 (range 100-1032); 742 (505-1247) ml, P = 0.313]. There was no difference in diuretic responses between patients with and without proteinuria. The serum level of albumin did not correlate with changes in urine output per day after tolvaptan treatment (P = 0.276, r = 0.156). Thus, additional administration of tolvaptan elicited a good diuretic response in HHF patients with hypoalbuminemia or proteinuria. These data suggest that tolvaptan might be beneficial for such HHF patients.

    DOI: 10.1007/s00380-017-1066-4

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  • Association between hypo- and hyperkalemia and outcome in acute heart failure patients: the role of medications. 国際誌

    Matthieu Legrand, Pierre-Olivier Ludes, Ziad Massy, Patrick Rossignol, Jiri Parenica, Jin-Joo Park, Shiro Ishihara, Khalid F AlHabib, Aldo Maggioni, Òscar Miró, Naoki Sato, Alain Cohen-Solal, Enrique Fairman, Johan Lassus, Veli-Pekka Harjola, Christian Mueller, Franck W Peacock, Dong-Ju Choi, Patrick Plaisance, Jindřich Spinar, Mikhail Kosiborod, Alexandre Mebazaa, Etienne Gayat

    Clinical research in cardiology : official journal of the German Cardiac Society   107 ( 3 )   214 - 221   2018年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The interaction between chronic medications on admission and the association between serum potassium level and outcome in patients with acute heart failure (AHF) are unknown. METHODS: Observational intercontinental study of patients admitted with AHF. 15954 patients were included from 12 cohorts in 4 continents. Main outcome was 90-day mortality. Clinical presentation (medication use, hemodynamics, comorbidities), demographic, echocardiographic, and biochemical data on admission were recorded prospectively in each cohort, with prospective adjudication of outcomes. RESULTS: Positive and negative linear relationships between 90-day mortality and sK+ above 4.5 mmol/L (hyperkalemia) and below 3.5 mmol/L (hypo-kalemia) were observed. Hazard ratio for death was 1.46 [1.34-1.58] for hyperkalemia and 1.22 [1.06-1.40] for hypokalemia. In a fully adjusted model, only hyperkalemia remained associated with mortality (HR 1.03 [1.02-1.04] for each 0.1 mmol/l change of sK+ above 4.5 mmol/L). Interaction tests revealed that the association between hyperkalemia and outcome was significantly affected by chronic medications. The association between hyperkalemia and mortality was absent for patients treated with beta blockers and in those with preserved renal function. CONCLUSIONS: In patients with AHF, sK+ > 4.5 mmol/L appears to be associated with 90-day mortality. B-blockers have potentially a protective effect in the setting of hyperkalemia.

    DOI: 10.1007/s00392-017-1173-3

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  • Heart failure oral therapies at discharge are associated with better outcome in acute heart failure: a propensity-score matched study. 国際誌

    Etienne Gayat, Mattia Arrigo, Simona Littnerova, Naoki Sato, Jiri Parenica, Shiro Ishihara, Jindrich Spinar, Christian Müller, Veli-Pekka Harjola, Johan Lassus, Òscar Miró, Aldo P Maggioni, Khalid F AlHabib, Dong-Ju Choi, Jin Joo Park, Yuhui Zhang, Jian Zhang, James L Januzzi Jr, Katsuya Kajimoto, Alain Cohen-Solal, Alexandre Mebazaa

    European journal of heart failure   20 ( 2 )   345 - 354   2018年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: Heart failure oral therapies (HFOTs), including beta-blockers (BB), renin-angiotensin system inhibitors (RASi) and mineralocorticoid receptor antagonists, administered before hospital discharge after acute heart failure (AHF) might improve outcome. However, concerns have been raised because early administration of HFOTs may worsen patient's condition. We hypothesized that HFOTs at hospital discharge might be associated with better post-discharge survival. METHODS AND RESULTS: The study population was composed of 19 980 AHF patients from the GREAT registry. The primary and secondary outcomes were 90-day and 1-year all-cause mortality, respectively. Survival was estimated with univariate and covariate-adjusted Cox proportional hazards regression models for the whole population and after propensity-score matching. HFOTs at discharge were consistently associated with no excess mortality in the unadjusted and adjusted analyses of the whole and matched cohorts. In the matched cohort, BB and RASi at discharge were associated with lower 90-day mortality risks compared to the respective untreated groups [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.46-0.69; and HR 0.53, 95% CI 0.42-0.66, respectively]. The favourable associations of BB and RASi at discharge with 90-day mortality were present in many subgroups including patients with reduced or preserved left ventricular ejection fraction and persisted up to 1 year after discharge. The combination of RASi and BB was associated with an even lower risk of death than RASi or BB alone. CONCLUSIONS: Administration of HFOTs at hospital discharge is associated with better survival of AHF patients.

    DOI: 10.1002/ejhf.932

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  • Reassessing Phase II Heart Failure Clinical Trials: Consensus Recommendations. 国際誌

    Javed Butler, Carine E Hamo, James E Udelson, Christopher O'Connor, Hani N Sabbah, Marco Metra, Sanjiv J Shah, Dalane W Kitzman, John R Teerlink, Harold S Bernstein, Gabriel Brooks, Christophe Depre, Mary M DeSouza, Wilfried Dinh, Mark Donovan, Regina Frische-Danielson, Robert J Frost, Dahlia Garza, Udo-Michael Gohring, Jennifer Hellawell, Judith Hsia, Shiro Ishihara, Patricia Kay-Mugford, Joerg Koglin, Marc Kozinn, Christopher J Larson, Martha Mayo, Li-Ming Gan, Pierrre Mugnier, Sekayi Mushonga, Lothar Roessig, Cesare Russo, Afshin Salsali, Carol Satler, Victor Shi, Barry Ticho, Michael van der Laan, Clyde Yancy, Norman Stockbridge, Mihai Gheorghiade

    Circulation. Heart failure   10 ( 4 )   2017年4月

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    記述言語:英語  

    The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans. A critical examination of the phase II trials in heart failure reveals multiple shortcomings in their concept, design, execution, and interpretation. To further a dialogue on the challenges and potential for improvement and the role of phase II trials in patients with heart failure, the Food and Drug Administration facilitated a meeting on October 17, 2016, represented by clinicians, researchers, industry members, and regulators. This document summarizes the discussion from this meeting and provides key recommendations for future directions.

    DOI: 10.1161/CIRCHEARTFAILURE.116.003800

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  • Precipitating factors and 90-day outcome of acute heart failure: a report from the intercontinental GREAT registry. 国際誌

    Mattia Arrigo, Etienne Gayat, Jiri Parenica, Shiro Ishihara, Jian Zhang, Dong-Ju Choi, Jin Joo Park, Khalid F Alhabib, Naoki Sato, Oscar Miro, Aldo P Maggioni, Yuhui Zhang, Jindrich Spinar, Alain Cohen-Solal, Theodore J Iwashyna, Alexandre Mebazaa

    European journal of heart failure   19 ( 2 )   201 - 208   2017年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: Several clinical conditions may precipitate acute heart failure (AHF) and influence clinical outcome. In this study we hypothesized that precipitating factors are independently associated with 90-day risk of death in AHF. METHODS AND RESULTS: The study population consisted of 15 828 AHF patients from Europe and Asia. The primary outcome was 90-day all-cause mortality according to identified precipitating factors of AHF [acute coronary syndrome (ACS), infection, atrial fibrillation (AF), hypertension, and non-compliance]. Mortality at 90 days was 15.8%. AHF precipitated by ACS or by infection showed increased 90-day risk of death compared with AHF without identified precipitants [hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.44-1.97, P < 0.001; and HR 1.51, 95% CI 1.18-1.92, P = 0.001), while AHF precipitated by AF showed lower 90-day risk of death (HR 0.56, 95% CI 0.42-0.75, P < 0.001), after multivariable adjustment. The risk of death in AHF precipitated by ACS was the highest during the first week after admission, while in AHF precipitated by infection the risk of death had a delayed peak at week 3. In AHF precipitated by AF, a trend toward reduced risk of death during the first weeks was shown. At weeks 5-6, AHF precipitated by ACS, infection, or AF showed similar risk of death to that of AHF without identified precipitants. CONCLUSIONS: Precipitating factors are independently associated with 90-day mortality in AHF. AHF precipitated by ACS or infection is independently associated with higher, while AHF precipitated by AF is associated with lower 90-day risk of death.

    DOI: 10.1002/ejhf.682

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  • Similar hemodynamic decongestion with vasodilators and inotropes: systematic review, meta-analysis, and meta-regression of 35 studies on acute heart failure. 国際誌

    Shiro Ishihara, Etienne Gayat, Naoki Sato, Mattia Arrigo, Said Laribi, Matthieu Legrand, Rui Placido, Philippe Manivet, Alain Cohen-Solal, William T Abraham, Mariell Jessup, Alexandre Mebazaa

    Clinical research in cardiology : official journal of the German Cardiac Society   105 ( 12 )   971 - 980   2016年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Acute heart failure (AHF) with reduced left-ventricular ejection fraction (LVEF) is often a biventricular congested state. The comparative effect of vasodilators and inotropes on the right- and/or left-sided congestion is unknown. METHODS AND RESULTS: A systematic review, meta-analysis, and meta-regression of AHF studies using pulmonary artery catheter were performed using PubMed, Embase, and Cochrane library. Data from 35 studies, including 3016 patients, were studied. Included patients had a weighted mean age of 60 years, left-ventricular ejection fraction (LVEF) of 24 %, and plasma B-type natriuretic peptide (BNP) of 892 pg/ml. Both the left- and right-ventricular filling pressures were elevated: weighted mean pulmonary artery wedge pressure (PAWP) was 25 mmHg (range 17-31 mmHg) and right atrial pressure (RAP) 12 mmHg (range 7-18 mmHg). Vasodilators and inotropes had similar beneficial effects on PAWP [-6.3 mmHg (95 % CI -7.4 to -5.2 mmHg) and -5.8 mmHg (95 % CI -7.6 to -4.0 mmHg), respectively] and RAP [-2.9 mmHg (95 % CI -3.8 to -2.1 mmHg) and -2.8 mmHg (95 % CI -3.8 to -1.7 mmHg), respectively]. Among inotropes, inodilators, such as levosimendan, have greater beneficial effect on the left-ventricular filling pressure than dobutamine. Drug-induced improvement of PAWP tightly paralleled that of RAP with all studied drugs (r 2 = 0.90, p < 0.001). Vasodilators and inotropes had no short-term effect of renal function. CONCLUSION: The left- and right-sided filling pressures are similarly improved by vasodilators or inotropes, in AHF with reduced LVEF.

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  • Natriuretic peptides in addition to Zwolle score to enhance safe and early discharge after acute myocardial infarction: A prospective observational cohort study. 国際誌

    Eva Ganovska, Mattia Arrigo, Katerina Helanova, Simona Littnerova, Malha Sadoune, Petr Kubena, Marie Pavlusova, Jiri Jarkovsky, Jana Gottwaldova, Petr Kala, Milan Dastych, Shiro Ishihara, Lucas N L Van Aelst, Alain Cohen-Solal, Etienne Gayat, Jindrich Spinar, Jiri Parenica, Alexandre Mebazaa

    International journal of cardiology   215   527 - 31   2016年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The Zwolle score is recommended to identify low-risk patients eligible for early hospital discharge after ST-elevation myocardial infarction (STEMI), but since only one third of STEMI has low Zwolle score, hospital discharge is frequently delayed. B-type natriuretic peptide (BNP) also provides prognostic information after STEMI. The aim of the study was to test the hypothesis that patients with high Zwolle score associated with low BNP share similar outcomes than those with low Zwolle score. METHODS AND RESULTS: The study population consisted of 1032 consecutive STEMI patients in whom BNP was measured 24h after chest pain onset. The area under the curve of Zwolle score and plasma BNP for 30-day mortality were 0.82 and 0.87, p=0.39. A BNP threshold of 200pg/ml had sensitivity of 100% and specificity of 34% for predicting 30-day mortality. Patients with high Zwolle score and BNP≤200pg/ml (n=183) had similar mortality and hospital stay to those with low Zwolle score (0% vs. 0.5% and 5 vs. 5days, both p=1.0). By contrast, patients with high Zwolle score and BNP>200pg/ml had the highest mortality (6.7%) and the longest hospital stay (6days), both p<0.01. CONCLUSION: STEMI patients with high Zwolle score but low BNP share similar outcomes with those with low Zwolle score and should be eligible for early discharge. Hence, using the rule of "low-Zwolle or low-BNP" might increase the number of STEMI patients that might be eligible for early discharge.

    DOI: 10.1016/j.ijcard.2016.04.148

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  • Clinical presentation and outcome by age categories in acute heart failure: results from an international observational cohort. 国際誌

    Antonio Teixeira, Jiri Parenica, Jin Joo Park, Shiro Ishihara, Khalid F AlHabib, Said Laribi, Aldo Maggioni, Òscar Miró, Naoki Sato, Katsuya Kajimoto, Alain Cohen-Solal, Enrique Fairman, Johan Lassus, Christian Mueller, William F Peacock, James L Januzzi Jr, Dong-Ju Choi, Patrick Plaisance, Jindrich Spinar, Alexandre Mebazaa, Etienne Gayat

    European journal of heart failure   17 ( 11 )   1114 - 23   2015年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: To assess, according to age groups, patients' characteristics according to region of origin, the chronic therapeutic management, prognostic utility of clinical variables, and natriuretic peptides. METHODS AND RESULTS: The GREAT registry consisted of patients identified as presenting with acute heart failure at the emergency department. Four groups of patients were defined according to age: the young patient group (<65 years); 'middle-old' (65-74 years), 'old-old' (75-84 years) and the 'oldest-old' (85-94 years). Follow-up at 1 year was performed via personal contact or national data registries at 1 year. Dataset consisted of 14 758 patients aged up to 95 years, with the 'oldest-old' group being more prevalent in North America and Western Europe. The 30-day mortality rate were, respectively, 8.1%, 8.9%, 10.3%, and 16.3% among the four age groups and 1-year mortality rates were, respectively, 3.1%, 17.1%, 24.7%, and 39.9%. Chronic heart failure treatment was less frequently administered with age (percentage of the 'fully treated' group was 14% in the 'young' compared with 2% in the 'oldest-old' patient group). Reduced left ventricular ejection fraction was present in 70%, 62.3%, 52.5%, and 46.8% among the four age groups, respectively. The prognostic utility of most variables for short- and long-term outcome was attenuated with age, with the exception of natriuretic peptides. CONCLUSION: This study found a large heterogeneity in age among geographic regions and that the eldest are less likely to be treated in accordance with recommendations of current heart failure guidelines. Natriuretic peptide concentrations retained prognostic value in patients across age strata.

    DOI: 10.1002/ejhf.330

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  • Long-term Hemodialysis Corrects Left Ventricular Dyssynchrony in End-stage Renal Disease: A Study with Gated Technetium-99m Sestamibi Myocardial Perfusion Single-photon Emission Computed Tomography (vol 82, pg 76, 2015) 査読

    Naoto Takahashi, Naoki Sato, Masahiro Ishikawa, Arifumi Kikuchi, Daisuke Hanaoka, Shiro Ishihara, Kenichi Amitani, Yukinao Sakai, Shin-ichiro Kumita, Wataru Shimizu

    JOURNAL OF NIPPON MEDICAL SCHOOL   82 ( 3 )   166 - 166   2015年6月

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    記述言語:英語   出版者・発行元:MEDICAL ASSOC NIPPON MEDICAL SCH  

    DOI: 10.1272/jnms.82.166

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  • Long-term Hemodialysis Corrects Left Ventricular Dyssynchrony in End-stage Renal Disease: A Study with Gated Technetium-99m Sestamibi Myocardial Perfusion Single-photon Emission Computed Tomography 査読

    Naoto Takahashi, Naoki Sato, Masahiro Ishikawa, Arifumi Kikuchi, Daisuke Hanaoka, Shiro Ishihara, Kenichi Amitani, Naoyuki Sakai, Shin-ichiro Kumita, Wataru Shimizu

    JOURNAL OF NIPPON MEDICAL SCHOOL   82 ( 2 )   76 - 83   2015年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:MEDICAL ASSOC NIPPON MEDICAL SCH  

    Introduction: Left ventricular (LV) dyssynchrony is common in patients with end-stage renal disease (ESRD), and echocardiographic assessment has shown that it can be improved by a single session of hemodialysis (HD). The aim of this study was to assess the effects of chronic HD on LV dyssynchrony in patients ESRD by means of gated technetium-99m sestamibi myocardial perfusion single-photon emission computed tomography (GSPECT) with phase analysis.
    Materials and Methods: Twelve patients with ESRD underwent GSPECT and echocardiography before the start of long-term HD (baseline) and 3 months later. In addition, 7 control subjects matched for age and sex underwent GSPECT and echocardiography within a 2-month period. To evaluate LV dyssynchrony, both histogram bandwidth (HBW) and phase standard deviation (PSD) were determined with phase analysis of GSPECT images. The end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction were also measured with GSPECT, and the LV mass index (LVMI) was measured with echocardiography. The LV dyssynchrony, volume, function, and mass were compared among control subjects, patients with ESRD at baseline, and patients with ESRD after 3 months of chronic HD.
    Results: The LV dyssynchrony, volume, and mass at baseline were significantly greater in patients with ESRD than in control subjects (HBW, 65.5 degrees+/-54.4 degrees vs. 22.3 degrees+/-7.5 degrees, P&lt;0.05; PSD, 21.00 degrees+/-15.50 degrees vs. 7.6 degrees+/-5.5 degrees, P&lt;0.05; EDV, 105.7+/-29.2 vs. 72.3+/-13.9 mL, P&lt;0.05; ESV, 44.3+/-22.1 vs. 20.9+/-10.3 mL, P&lt;0.05; LVMI, 136.5+/- 48.3 vs. 65.4+/-5.6 g/m(2), P&lt;0.01). From baseline to the third month of chronic HD, there were significant increases in EDV (78.6+/-25.4 vs. 105.7+/-29.2 mL, P&lt;0.01) and ESV (27.6+/-16.2 vs. 44.3+/-22.1 mL, P&lt;0.01) and significant decreases in HBW (65.5 degrees+/-54.4 degrees vs. 31.0 degrees+/-15.7 degrees, P&lt;0.01) and PSD (21.0 degrees+/-15.5 degrees vs. 10.00 degrees+/-8.2 degrees, P&lt;0.01).
    Conclusion: Chronic HD decreased LV dyssynchrony and volume in patients with ESRD. Serial phase analysis of GSPECT images is a useful method of assessing the effects of long-term HD on LV dyssynchrony and volume in patients with ESRD.

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  • Prognostic markers of acute decompensated heart failure: the emerging roles of cardiac biomarkers and prognostic scores. 国際誌

    Alain Cohen-Solal, Said Laribi, Shiro Ishihara, Giuseppe Vergaro, Mathilde Baudet, Damien Logeart, Alexandre Mebazaa, Etienne Gayat, Nicolas Vodovar, Domingo A Pascual-Figal, Marie-France Seronde

    Archives of cardiovascular diseases   108 ( 1 )   64 - 74   2015年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Rapidly assessing outcome in patients with acute decompensated heart failure is important but prognostic factors may differ from those used routinely for stable chronic heart failure. Multiple plasma biomarkers, besides the classic natriuretic peptides, have recently emerged as potential prognosticators. Furthermore, prognostic scores that combine clinical and biochemical data may also be useful. However, compared with the scores used in chronic heart failure, scores for acute decompensated heart failure have not been validated. This article reviews potential biomarkers, with a special focus on biochemical biomarkers, and possible prognostic scores that could be used by the clinician when assessing outcome in patients with acute heart failure.

    DOI: 10.1016/j.acvd.2014.10.002

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  • Post-translational modifications enhance NT-proBNP and BNP production in acute decompensated heart failure. 国際誌

    Nicolas Vodovar, Marie-France Séronde, Said Laribi, Etienne Gayat, Johan Lassus, Riadh Boukef, Semir Nouira, Philippe Manivet, Jane-Lise Samuel, Damien Logeart, Shiro Ishihara, Alain Cohen Solal, James L Januzzi Jr, A Mark Richards, Jean-Marie Launay, Alexandre Mebazaa

    European heart journal   35 ( 48 )   3434 - 41   2014年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Increases in plasma B-type natriuretic peptide (BNP) concentrations in those with acutely decompensated heart failure (ADHF) has been mainly attributed to an increase in NPPB gene transcription. Recently, proBNP glycosylation has emerged as a potential regulatory mechanism in the production of amino-terminal (NT)-proBNP and BNP. The aim of the present study was to investigate proBNP glycosylation, and corin and furin activities in ADHF patients. METHODS AND RESULTS: Plasma levels of proBNP, NT-proBNP, BNP, as well as corin and furin concentration and activity were measured in a large cohort of 683 patients presenting with ADHF (n = 468), non-cardiac dyspnoea (non-ADHF: n = 169) and 46 patients with stable chronic heart failure (CHF); the degree of plasma proBNP glycosylation was assessed in a subset of these patients (ADHF: n = 49, non-ADHF: n = 50, CHF: n = 46). Our results showed a decrease in proBNP glycosylation in ADHF patients that paralleled NT-proBNP overproduction (ρ = -0.62, P < 0.001) but less so to BNP. In addition, we observed an increase in furin activity that is positively related to the plasma levels of proBNP, NT-proBNP and BNP overproduction (all P < 0.001, all ρ > 0.88), and negatively related to the degree of proBNP glycosylation (ρ = -0.62, P < 0.001). CONCLUSION: These comprehensive results provide a paradigm for the post-translational modification of natriuretic peptides in ADHF: as proBNP glycosylation decreases, furin activity increases. This synergistically amplifies the processing of proBNP into BNP and NT-proBNP. CLINICAL TRIAL REGISTRATION: http://clinicaltrials.gov/. Identifier: NCT01374880.

    DOI: 10.1093/eurheartj/ehu314

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  • Body mass index and mortality in acutely decompensated heart failure across the world: a global obesity paradox. 国際誌

    Ravi Shah, Etienne Gayat, James L Januzzi Jr, Naoki Sato, Alain Cohen-Solal, Salvatore diSomma, Enrique Fairman, Veli-Pekka Harjola, Shiro Ishihara, Johan Lassus, Aldo Maggioni, Marco Metra, Christian Mueller, Thomas Mueller, Jiri Parenica, Domingo Pascual-Figal, William Frank Peacock, Jindrich Spinar, Roland van Kimmenade, Alexandre Mebazaa

    Journal of the American College of Cardiology   63 ( 8 )   778 - 85   2014年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    OBJECTIVES: This study sought to define the relationship between body mass index (BMI) and mortality in heart failure (HF) across the world and to identify specific groups in whom BMI may differentially mediate risk. BACKGROUND: Obesity is associated with incident HF, but it is paradoxically associated with better prognosis during chronic HF. METHODS: We studied 6,142 patients with acute decompensated HF from 12 prospective observational cohorts followed-up across 4 continents. Primary outcome was all-cause mortality. Cox proportional hazards models and net reclassification index described associations of BMI with all-cause mortality. RESULTS: Normal-weight patients (BMI 18.5 to 25 kg/m(2)) were older with more advanced HF and lower cardiometabolic risk. Despite worldwide heterogeneity in clinical features across obesity categories, a higher BMI remained associated with decreased 30-day and 1-year mortality (11% decrease at 30 days; 9% decrease at 1 year per 5 kg/m(2); p < 0.05), after adjustment for clinical risk. The BMI obtained at index admission provided effective 1-year risk reclassification beyond current markers of clinical risk (net reclassification index 0.119, p < 0.001). Notably, the "protective" association of BMI with mortality was confined to persons with older age (>75 years; hazard ratio [HR]: 0.82; p = 0.006), decreased cardiac function (ejection fraction <50%; HR: 0.85; p < 0.001), no diabetes (HR: 0.86; p < 0.001), and de novo HF (HR: 0.89; p = 0.004). CONCLUSIONS: A lower BMI is associated with age, disease severity, and a higher risk of death in acute decompensated HF. The "obesity paradox" is confined to older persons, with decreased cardiac function, less cardiometabolic illness, and recent-onset HF, suggesting that aging, HF severity/chronicity, and metabolism may explain the obesity paradox.

    DOI: 10.1016/j.jacc.2013.09.072

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  • Low diastolic blood pressure was one of the independent predictors of ischemia-like findings of electrocardiogram in patients who underwent coronary angiography. 国際誌

    Shinichiro Fujishima, Noboru Murakami, Yoshie Haga, Eiji Nyuta, Yuuki Nakate, Shiro Ishihara, Shigeru Kaseda, Tokushi Koga, Takao Ishitsuka

    Journal of cardiology   62 ( 4 )   230 - 5   2013年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: The underlying cause of a high cardiovascular event rate in the population with low diastolic blood pressure (DBP) has not been fully elucidated. METHODS AND RESULTS: The relationship between DBP and ischemia-like findings on electrocardiography (ECG) was investigated in 187 patients who underwent coronary angiography. Patients with conditions affecting ECG (e.g. patients taking digitalis or those with old myocardial infarction, complete right bundle branch block, or hypokalemia) were excluded from the analyses. Ischemia-like ECG was defined as having one or more of the following: borderline Q wave [Minnesota code (MC) I 3], ST depression (MC IV 1-3), negative T wave (MC V 1-3), and complete left bundle branch block (MC VII 1). Based on this definition, 70 of 187 patients (37%) had ischemia-like ECG. Compared with the group without it, the group with ischemia-like ECG included more females (p<0.01), and had lower values of body mass index (p = 0.01), DBP (p<0.01), estimated glomerular filtration rate (p<0.01), left ventricular ejection fraction (LVEF; p<0.01), and higher values of age (p<0.01) and left ventricular mass index (LVMI; p<0.01). The severity of coronary artery disease did not differ between the groups. Receiver operating characteristics curve analysis revealed that 74.5 mmHg was the optimal cut-off point of DBP to predict ischemia-like ECG (area under curve, 0.63; 95% confidence interval, 0.55-0.71, p = 0.003). There were no significant relationships between systolic blood pressure and ischemia-like ECG. A multivariate analysis showed that female sex, low DBP (≤ 74.5 mmHg), LVMI, and LVEF were the significant factors for the ischemia-like ECG. The odds ratio of low DBP was 2.53 (95% confidence interval, 1.19-5.40; p = 0.02). CONCLUSIONS: Low DBP was one of the significant predictors of the ischemia-like ECG in the present study. Myocardial ischemia may be a part of the cause of high cardiovascular morbidity in the population with low DBP.

    DOI: 10.1016/j.jjcc.2013.05.005

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  • Effects of intravenous nicorandil on the mid-term prognosis of patients with acute heart failure syndrome.

    Shiro Ishihara, Tokushi Koga, Shigeru Kaseda, Eiji Nyuta, Yoshie Haga, Shinichiro Fujishima, Takao Ishitsuka, Seizo Sadoshima

    Circulation journal : official journal of the Japanese Circulation Society   76 ( 5 )   1169 - 76   2012年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Acute heart failure syndrome (AHFS) remains a major clinical challenge because of its poor prognosis. Nicorandil, a hybrid compound of a potassium-channel opener and nitric oxide donor, has been reported to improve the prognosis of ischemic heart disease. We sought to evaluate the effect of intravenous nicorandil on the mid-term prognosis of AHFS. METHODS AND RESULTS: A total of 402 consecutive patients who were hospitalized for AHFS were divided into 2 groups according to the use of intravenous nicorandil: 78 patients in the Nicorandil group and 324 patients in the Control group. During the 180-day follow-up, death or rehospitalization for heart failure occurred in 7 patients in the Nicorandil group (9.0%) and in 75 patients (23.2%) in the Control group. Event-free survival rates were significantly higher in the Nicorandil group than in the Control group (P=0.006). Multivariate Cox hazard analysis revealed that age (hazard ratio (HR)=1.066, P<0.0001), systolic blood pressure (HR=0.983, P=0.0023), New York Heart Association class III/IV (HR=6.550, P<0.0001), log creatinine (HR=3.866, P=0.0106), and use of intravenous nicorandil (HR=0.179, P<0.0001) were significant predictive factors for the occurrence of death or rehospitalization for heart failure. CONCLUSIONS: Intravenous nicorandil treatment from the urgent phase of AHFS may improve the prognosis.

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  • Correlation between increased urinary sodium excretion and decreased left ventricular diastolic function in patients with type 2 diabetes mellitus. 国際誌

    Shuntaro Kagiyama, Tokushi Koga, Shigeru Kaseda, Shiro Ishihara, Nobuyuki Kawazoe, Seizo Sadoshima, Kiyoshi Matsumura, Yutaka Takata, Takuya Tsuchihashi, Mitsuo Iida

    Clinical cardiology   32 ( 10 )   569 - 74   2009年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Increased salt intake may induce hypertension, lead to cardiac hypertrophy, and exacerbate heart failure. When elderly patients develop heart failure, diastolic dysfunction is often observed, although the ejection fraction has decreased. Diabetes mellitus (DM) is an established risk factor for heart failure. However, little is known about the relationship between cardiac function and urinary sodium excretion (U-Na) in patients with DM. METHODS: We measured 24-hour U-Na; cardiac function was evaluated directly during coronary catheterization in type 2 DM (n = 46) or non-DM (n = 55) patients with preserved cardiac systolic function (ejection fraction > or = 60%). Cardiac diastolic and systolic function was evaluated as - dp/dt and + dp/dt, respectively. RESULTS: The average of U-Na was 166.6 +/- 61.2 mEq/24 hour (mean +/- SD). In all patients, stepwise multivariate regression analysis revealed that - dp/dt had a negative correlation with serum B-type natriuretic peptide (BNP; beta = - 0.23, P = .021) and U-Na (beta = - 0.24, P = .013). On the other hand, + dp/dt negatively correlated with BNP (beta = - 0.30, P < .001), but did not relate to U-Na. In the DM-patients, stepwise multivariate regression analysis showed that - dp/dt still had a negative correlation with U-Na (beta = - 0.33, P = .025). CONCLUSION: The results indicated that increased urinary sodium excretion is associated with an impairment of cardiac diastolic function, especially in patients with DM, suggesting that a reduction of salt intake may improve cardiac diastolic function.

    DOI: 10.1002/clc.20664

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  • Transient precordial ST elevation by a spasm of the conus artery during right coronary angiography. 国際誌

    Shuntaro Kagiyama, Tokushi Koga, Shigeru Kaseda, Shiro Ishihara, Nobuyuki Kawazoe, Seizo Sadoshima

    International journal of cardiology   116 ( 2 )   e57-9   2007年3月

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    記述言語:英語  

    During coronary angiography of right coronary artery (RCA), a catheter wedged into a conus artery, and a remarkable coved-type ST elevation was seen in precordial lead through V1-3. LCA angiography did not show any abnormal findings, but we recognized a slow contrast flow in a conus artery by RCA angiography. The patient was free from chest pain, and a ST elevation was improved. The slow flow of a conus artery was recovered within five minutes. Precordial ST elevation may be caused by a catheter-induced spasm of a conus artery.

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