Significance of genetic mutation in pulmonary hypertension and its relationship with right ventricular failure

• Project/Area Number: 17K09525
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Tokai University (2019); Keio University (2017-2018)
• Principal Investigator: MURATA Mitsushige 東海大学, 医学部, 教授 (30317135)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 右室機能 / 肺高血圧 / 臨床心臓学

Outline of Final Research Achievements

The carrier of bone morphogenetic protein (BMP) type II receptor (BMPR-II) mutation implicates poor prognosis in pulmonary hypertension. However, we previously reported that the prognosis after combination therapy would be better in mutation carrier than in noncarrier. In this study, an analysis of 26 cases of idiopathic pulmonary hypertension (IPAH) (7 cases with BMPR2 gene mutation positive and 19 cases with negative) showed that baseline right ventricular function was better in carrier than in noncarrier, but the right ventricular function after combination therapy was significantly better in the carrier than in the noncarrier.

Academic Significance and Societal Importance of the Research Achievements

右室機能は、肺高血圧症において独立した予後規定因子であることが報告されている。しかし、治療により右室機能がどのように改善するか不明である。Bone morphogenetic protein (BMP) type II receptor (BMPR-II)遺伝子異常を有すると予後不良として知られているが、本研究では、BMPR-II遺伝子異常は薬剤による右室機能改善に影響がある可能性を示した。

Research Products

• [Journal Article] Characteristics of Chronic Obstructive Pulmonary Disease Patients with Pulmonary Hypertension Assessed by Echocardiography in a Three-Year Observational Cohort Study (2020)
  • Author(s): Nakayama S, Chubachi S, Sakurai K, Irie H, Tsutusmi A, Hashiguchi M, Itabashi Y, Murata M, Nakamura H, Asano K, Fukunaga K
  • Journal Title: Int J Chron Obstruct Plmon Dis Volume: 15 Pages: 487-499
  • DOI: 10.2147/copd.s230952
  • Peer Reviewed / Open Access
• [Journal Article] Significance of echocardiographic evaluation for transcatheter aortic valve implantation. (2020)
  • Author(s): Shirakawa K, Murata M
  • Journal Title: Cardiovasc Interv Ther Volume: 35 Issue: 1 Pages: 85-95
  • DOI: 10.1007/s12928-019-00617-6
  • NAID: 40022130049
  • Peer Reviewed
• [Journal Article] A tale of two sisters with hypertrophic cardiomyopathy and recurrent embolism: When is the optimal timing of the intervention for left atrial appendage? (2019)
  • Author(s): Kimura Mai、Kohno Takashi、Makino Shinji、Okuda Shigeo、Nawata Kan、Yanagisawa Ryo、Kojima Hidenori、Nishiyama Takahiko、Aizawa Yoshiyasu、Yuasa Shinsuke、Murata Mitsushige、Maekawa Yuichiro、Okamoto Kazuma、Shimizu Hideyuki、Fukuda Keiichi
  • Journal Title: Heart & Lung Volume: 48 Issue: 3 Pages: 198-200
  • DOI: 10.1016/j.hrtlng.2018.08.010
  • Peer Reviewed / Open Access
• [Journal Article] Shortening Hospital Stay Is Feasible and Safe in Patients With Chronic Thromboembolic Pulmonary Hypertension Treated With Balloon Pulmonary Angioplasty (2019)
  • Author(s): Kimura Mai、Kohno Takashi、Kawakami Takashi、Kataoka Masaharu、Hiraide Takahiro、Moriyama Hidenori、Isobe Sarasa、Tsugu Toshimitsu、Itabashi Yuji、Murata Mitsushige、Yuasa Shinsuke、Fukuda Keiichi
  • Journal Title: Canadian Journal of Cardiology Volume: 35 Issue: 2 Pages: 193-198
  • DOI: 10.1016/j.cjca.2018.12.001
  • Peer Reviewed
• [Journal Article] Right Ventricle-Specific Three-Dimensional Wall Motion Tracking for Visualization of Regional Wall Motion Abnormality in Patients With Pulmonary Arterial Hypertension (2019)
  • Author(s): Moriyama Hidenori、Murata Mitsushige、Kataoka Masaharu、Kawakami Takashi、Endo Jin、Kohno Takashi、Itabashi Yuji、Seo Yoshihiro、Iwao Yasushi、Fukuda Keiichi
  • Journal Title: Circulation: Cardiovascular Imaging Volume: 12 Issue: 4
  • DOI: 10.1161/circimaging.118.008795
  • Peer Reviewed
• [Journal Article] Improvement in the electrocardiograms associated with right ventricular hypertrophy after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension (2018)
  • Author(s): Nishiyama Takahiko、Takatsuki Seiji、Kawakami Takashi、Katsumata Yoshinori、Kimura Takehiro、Kataoka Masaharu、Tsuruta Hikaru、Itabashi Yuji、Murata Mitsushige、Yuasa Shinsuke、Aizawa Yoshiyasu、Fukuda Keiichi
  • Journal Title: IJC Heart & Vasculature Volume: 19 Pages: 75-82
  • DOI: 10.1016/j.ijcha.2018.05.003
  • Peer Reviewed / Open Access
• [Journal Article] Riociguat, a soluble guanylate cyclase stimulator, ameliorates right ventricular contraction in pulmonary arterial hypertension (2017)
  • Author(s): Murata Mitsushige、Kawakami Takashi、Kataoka Masaharu、Kohno Takashi、Itabashi Yuji、Fukuda Keiichi
  • Journal Title: Pulmonary Circulation Volume: 8 Issue: 1 Pages: 1-4
  • DOI: 10.1177/2045893217746111
  • Peer Reviewed
• [Journal Article] The clinical value of assessing right ventricular diastolic function after balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension (2017)
  • Author(s): Moriyama Hidenori、Murata Mitsushige、Tsugu Toshimitsu、Kawakami Takashi、Kataoka Masaharu、Hiraide Takahiro、Kimura Mai、Isobe Sarasa、Endo Jin、Kohno Takashi、Itabashi Yuji、Fukuda Keiichi
  • Journal Title: The International Journal of Cardiovascular Imaging Volume: - Issue: 6 Pages: 875-882
  • DOI: 10.1007/s10554-017-1296-7
  • Peer Reviewed
• [Presentation] Riociguat ameliorates right ventricular function assessed by speckle-tracking echocardiography in patients with pulmonary hypertension. (2019)
  • Author(s): Murata M, Kawakami T, Kataoka M, Moriyama H, Hiraide T, Kimura M, Endo J, Kohno T, Itabashi Y, Fukuda K
  • Organizer: 68th Annual Scientific Session and Expo of the American College of Cardiology
  • Int'l Joint Research
• [Presentation] 肺高血圧症における右室３次元speckle-tracking法による右室機能評価と右室局所壁運動異常の臨床的意義 (2019)
  • Author(s): 守山英則、村田光繁、川上崇史、片岡雅晴、木村舞、平出貴裕、遠藤仁、河野隆志、板橋裕史、瀬尾由広、岩男泰、福田恵一
  • Organizer: 第30回日本心エコー図学会
• [Presentation] High-sensitive cardiac troponin T level is a surrogate marker for RV functional recovery after successful balloon pulmonary angioptasty in patients with chronic thromboembolic pulmonary hypertension (2018)
  • Author(s): Murata M, Tsugu T, Hiraide T, Moriyama H, Kimura M, Isobe S, Kawakami T, Kataoka M, Kohno T, Itabashi Y, Fukuda K
  • Organizer: 6th World Symposium on Pulmonary Hypertension
  • Int'l Joint Research
• [Presentation] The clinical value of assessing right ventricular diastolic function after balloon pulmonary angioptasty in patients with chronic thromboembolic pulmonary hypertension (2018)
  • Author(s): Moriyama H, Murata M, Tsugu T, Kawakami T, Kataoka M, Hiraide T, Kimura M, Isobe S, Endo J, Kohno T, Itabashi Y, Fukuda K
  • Organizer: 6th World Symposium on Pulmonary Hypertension
  • Int'l Joint Research
• [Presentation] The effects of bone morphogenetic protein receptor type 2 mutation on right ventricular function in pulmonary arterial hypertension after optimal combination therapy (2018)
  • Author(s): Hiraide T, Murata M, Kataoka M, Yuki A, Isobe S, Kawakami T, Moriyama H, Endo J, Itabashi Y, Gamou S, Fukuda K
  • Organizer: 6th World Symposium on Pulmonary Hypertension
  • Int'l Joint Research
• [Presentation] 肺高血圧症の右室機能評価における三次元右室wall motion tracking法の有用性について (2017)
  • Author(s): 村田光繁、川上崇史、片岡雅晴、瀬尾由広、南方友吾、遠藤仁、鶴田ひかる、 板橋裕史、福田恵一
  • Organizer: 第28回日本心エコー図学会
• [Presentation] 右室strain rateを用いた右室拡張機能評価の有用性について～慢性肺血栓塞栓性肺高血圧症における検討 (2017)
  • Author(s): 守山英則、村田光繁、繼敏光、川上崇史、平出貴裕、南方友吾、遠藤仁、 片岡雅晴、鶴田ひかる、板橋裕史、福田恵一
  • Organizer: 第28回日本心エコー図学会
• [Presentation] 慢性血栓塞栓性肺高血圧における運動耐容能と右室ストレインの関連について (2017)
  • Author(s): 継敏光、村田光繁、川上崇史、三田村秀雄、福田恵一
  • Organizer: 第90回日本超音波医学会学術集会
• [Presentation] 特発性肺高血圧症でのBMPR2遺伝子異常と右室機能の関連について (2017)
  • Author(s): 平出貴裕、村田光繁、片岡雅晴、川上崇史、磯部更紗、福田恵一
  • Organizer: 第2回日本肺高血圧・肺循環学会学術集会
• [Presentation] Riociguat ameliorates right ventricular function in patients with pulmonary hypertension (2017)
  • Author(s): Murata M, Kawakami T, Kataoka M, Minakata Y, Endo J, Tsuruta H, Itabashi Y, Maekawa Y, Fukuda K, Murata M
  • Organizer: European Society of Cardiology Congress
• [Presentation] Right ventricular strain preeicts exercise tolerance after balloon pulmonary angioplasty in patients with pulmonary hypertension (2017)
  • Author(s): Tsugu T, Murata M, Kawakami T, Kataoka M, Minakata Y, Tsuruta H, Itabashi Y, Maekawa Y, Mitamura H, Fukuda K
  • Organizer: European Society of Cardiology Congress
• [Presentation] Right ventricular diastolic strain rate reflects right ventricular diastolic function in patients with chronic thromboembolic pulmonary hypertension (2017)
  • Author(s): Moriyama H, Tsugu T, Murata M, Kawakami T, Kataoka M, Minakata Y, Endo J, Tsuruta H, Itabashi Y, Fukuda K
  • Organizer: European Society of Cardiology Congress