Development of comprehensive treatment of heart failure, hypertrophy, and arrhythmia by regulating intracellular Ca

• Project/Area Number: 23390215
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Yamaguchi University
• Principal Investigator: YANO Masafumi 山口大学, 医学(系)研究科(研究院), 教授 (90294628)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Shigeki 山口大学, 医学部附属病院, 講師 (90397993) ; 池田 安宏 山口大学, 医学(系)研究科(研究院), 助教 (00260349)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000); Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000); Fiscal Year 2011: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 心不全 / 筋小胞体 / カルシウム / リアノジン受容体 / EC-coupling / Ryanodine receptor / Calmodulin / CPVT

Research Abstract

In this three years, we revealed that basic mechanism of arrhythmogenesity in CPVT and pressure overload HF is Ca leak from SR. The underlying mechanism of Ca leak is unzipping of channel reguratory domains and CaM binding domain. We also investigate the dantrolene, zipper of the channel reguratory domains and high affinity CaM as a therapeutic agents.

Research Products

• [Journal Article] Enhanced binding of calmodulin to RyR2 corrects arrhythmogenic channel disorder in CPVT-associated myocytes (2014)
  • Author(s): Fukuda M, Yamamoto T, Nishimura S, Kato T, Murakami W, Hino A, Ono M, Tateishi H, Oda T, Okuda S, Kobayashi S, Koseki N, Kyushiki H, Yano M
  • Journal Title: Biochem Biophys Res Commun Volume: 448(1) Issue: 1 Pages: 1-7
  • DOI: 10.1016/j.bbrc.2014.03.152
  • Peer Reviewed / Open Access
• [Journal Article] A low-dose β 1-blocker effectively and safely slows the heart rate in patients with acute decompensated heart failure and rapid atrial fibrillation (2014)
  • Author(s): Kobayashi S, Murakami W, Myoren T, Tateishi H, Okuda S, Doi M, Nao T, Wada Y, Matsuzaki M, Yano M
  • Journal Title: Cardiology Volume: 127(2) Issue: 2 Pages: 105-13
  • DOI: 10.1159/000355312
  • Peer Reviewed
• [Journal Article] Serial three-dimensional optical coherence tomography assessment of strut coverage and intraluminal structures after drug-eluting stent implantation (2014)
  • Author(s): Maeda T, Okamura T, Yamada J, Nao T, Tateishi H, Yoshimura M, Oda T, Shiraishi K, Nakashima T, Nakamura T, Miura T, Yano M
  • Journal Title: Cardiovasc Interv Ther Volume: 29(1) Issue: 1 Pages: 31-9
  • DOI: 10.1007/s12928-013-0209-5
  • Peer Reviewed
• [Journal Article] Sarcomere Gene Mutations Are Associated With Increased Cardiovascular Events in Left Ventricular Hypertrophy : Results From Multicenter Registration in Japan. (2013)
  • Author(s): Fujita T, Komuro I (18人中13番目）
  • Journal Title: JACC Heart Fail Volume: 6 Issue: 6 Pages: 459-466
  • DOI: 10.1016/j.jchf.2013.08.007
  • Peer Reviewed
• [Journal Article] Efficacy and safety of a 60-week treatment with candesartan in Japanese patients with mild to moderate chronic heart failure (2013)
  • Author(s): Masunori Matsuzaki, Kazuhiro Yamamoto, Masafumi Yano, Koki Nakamura, Yuko Miyata, Kenkichi Sugiura, Emi Nakata, Hiroyuki Tsutsui
  • Journal Title: J Cardiol Volume: 61 Pages: 267-274
  • NAID: 10031187799
  • Peer Reviewed
• [Journal Article] New Data on Catecholaminergic Polymorphic Ventricular Tachycardia in Japan (2013)
  • Author(s): Shinichi Okuda, Masafumi Yano
  • Journal Title: Circulation Journal Volume: 77 Issue: 7 Pages: 1684-1686
  • DOI: 10.1253/circj.CJ-13-0623
  • NAID: 10031173744
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Does a ripple of Ca(2+) leak develop into a rogue wave that can trigger pathological hypertrophy? (2012)
  • Author(s): Yano M, Okuda S
  • Journal Title: J Am Coll Cardiol Volume: 63(15) Issue: 15 Pages: 1580-2
  • DOI: 10.1016/j.jacc.2013.10.064
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced binding of calmodulin to the ryanodine receptor corrects contractile dysfunction in failing hearts (2012)
  • Author(s): Hino A, Yano M, Kato T, Fukuda M, Suetomi T, Ono M, Murakami W, Susa T, Okuda S, Doi M, Kobayashi S, Yamamoto T, Koseki N, Kyushiki H, Ikemoto N, Matsuzaki M
  • Journal Title: Cardiovasc Res Volume: 96(3) Issue: 3 Pages: 433-43
  • DOI: 10.1093/cvr/cvs271
  • Peer Reviewed
• [Journal Article] Low-dose β -blocker in combination with milrinone safely improves cardiac function and eliminates pulsus alternans in patients with acute decompensated heart failure (2012)
  • Author(s): Kobayashi S, Susa T, Tanaka T, Murakami W, Fukuta S, Okuda S, Doi M, Wada Y, Nao T, Yamada J, Okamura T, Yano M, Matsuzaki M
  • Journal Title: Circ J Volume: 76(7) Pages: 1646-53
  • NAID: 10030503344
  • Peer Reviewed
• [Journal Article] Urinary 8-hydroxy-2' -deoxyguanosine as a novel biomarker for predicting cardiac events and evaluating the effectiveness of carvedilol treatment in patients with chronic systolic heart failure (2012)
  • Author(s): Susa T, Kobayashi S, Tanaka T, Murakami W, Akashi S, Kunitsugu I, Okuda S, Doi M, Wada Y, Nao T, Yamada J, Ueyama T, Okamura T, Yano M, Matsuzaki M
  • Journal Title: Circ J Volume: 76(1) Pages: 117-26
  • NAID: 10030034360
  • Peer Reviewed
• [Journal Article] Low-Dose β-Blocker in Combination With Milrinone Safely Improves Cardiac Function and Eliminates Pulsus Alternans in Patients With Acute Decompensated Heart Failure (2012)
  • Author(s): Shigeki Kobayashi et al
  • Journal Title: Circulation Journal Volume: 76 Issue: 7 Pages: 1646-1653
  • DOI: 10.1253/circj.CJ-12-0033
  • NAID: 10030503344
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Urinary 8-Hydroxy-2'-Deoxyguanosine as a Novel Biomarker for Predicting Cardiac Events and Evaluating the Effectiveness of Carvedilol Treatment in Patients With Chronic Systolic Heart Failure (2012)
  • Author(s): Susa T, et al
  • Journal Title: Circulation Journal Volume: 76 Issue: 1 Pages: 117-126
  • DOI: 10.1253/circj.CJ-11-0537
  • NAID: 10030034360
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed
• [Journal Article] Mutation-linked defective interdomain interactions within ryanodine receptor cause aberrant Ca²+ release leading to catecholaminergic polymorphic ventricular tachycardia (2011)
  • Author(s): Suetomi T, Yano M, Uchinoumi H, Fukuda M, Hino A, Ono M, Xu X, Tateishi H, Okuda S, Doi M, Kobayashi S, Ikeda Y, Yamamoto T, Ikemoto N, Matsuzaki M
  • Journal Title: Circulation Volume: 124(6) Pages: 682-94
  • Peer Reviewed
• [Journal Article] Alterations in adhesion junction precede gap junction remodeling during the development of heart failure in cardiomyopathic hamster (2011)
  • Author(s): Yoshida M, Ohkusa T, Nakashima T, Takanari H, Yano M, Takemura G, Honjo H, Kodama I, Mizukami Y, Matsuzaki, M
  • Journal Title: Cardiovasc.Res Volume: Oct 1;92(1) Issue: 1 Pages: 95-105
  • DOI: 10.1093/cvr/cvr182
  • Peer Reviewed
• [Journal Article] Urinary 8-hydroxy-2'-deoxyguanosine reflects symptomatic status and severity of systolic dysfunction in patients with chronic heart failure (2011)
  • Author(s): Shigeki Kobayashi
  • Journal Title: European Journal of Heart Faililure Volume: 13 Issue: 1 Pages: 29-36
  • DOI: 10.1093/eurjhf/hfq178
  • Peer Reviewed
• [Journal Article] Mutation-linked defective interdomain interactions within ryanodine receptor cause aberrant Ca^<2+> release leading to catecholaminergic polymorphic ventricular tachycardia (2011)
  • Author(s): Takeshi Suetomi
  • Journal Title: Circulation Volume: 124 Issue: 6 Pages: 682-694
  • DOI: 10.1161/circulationaha.111.023259
  • Peer Reviewed
• [Presentation] Relationship between Cardiac 18F-FDG-PET/CT Imaging and Urinary 8-hydroxy-2'-deoxyguanosine as a Biomarker of Oxidative Stress in Patients with Cardiac Sarcoidosis (2014)
  • Author(s): Shigeki Kobayashi, Wakako Murakami, Takeki Myoren, Masakazu Fukuda, Kosuke Uchida, Makoto Ohno, Hiroki Tateishi, Tetsuro Oda, Ryosuke Kametani, Tomoko Nao, Yasuhiro Yoshiga, Jutaro Yamada, Takeshi Ueyama, Takayuki Okamura, Masafumi Yano
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京（東京国際フォーラム）
• [Presentation] Mapping the Binding Site of RyR2 “Unzipping” Peptide (DPc10) by Fluorescence Resonance Energy Transfer (FRET) in Permeabilized Cardiomyocytes (2014)
  • Author(s): Tetsuro Oda, Takeshi Yamamoto, Shigehiko Nishimura, Takayoshi Katoh, Masakazu Fukuda, Shinichi Okuda, Shigeki Kobayashi, Masafumi Yano
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京（東京国際フォーラム）
• [Presentation] Cardiomyocyte Ryanodine Receptor (RyR2) Oxidation in situ Causes Defective Interdomain Interaction and Reduces Calmodulin (CaM) Binding (2014)
  • Author(s): Tetsuro Oda, Takeshi Yamamoto, Shigehiko Nishimura, Takayoshi Katoh, Masakazu Fukuda, Shinichi Okuda, Shigeki Kobayashi, Masafumi Yano
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京（東京国際フォーラム）
• [Presentation] Dantrolene may Suppress Arrhythmogenesis by Inhibition of CaMKII-mediated Aberrant Ca2+ Release within Ryanodine Receptor in Cardiac Troponin T-related Hypertrophic Cardiomyopathy (2014)
  • Author(s): Shinichi Okuda, Masakazu Fukuda, Takayoshi Katoh, Shigehiko Nishimura, Shigeki Kobayashi, Takeshi Yamamoto, Masafumi Yano
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京（東京国際フォーラム）
• [Presentation] Dantrolene Corrects Aberrant Ca2+ Release and Improves Calmodulin Bindingto RyR2 in CPVT-associated Mutation (2014)
  • Author(s): Masakazu Fukuda, Takeshi Yamamoto, Shigehiko Nishimura, Takayoshi Katoh, Shinichi Okuda, Tetsurou Oda, Shigeki Kobayashi, Masafumi Yano
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京（東京国際フォーラム）
• [Presentation] Enhanced Binding of Calmodulin to the Ryanodine Receptor Corrects Abnormal Calcium Handling in Pressure Over Loaded Heart Failure (2014)
  • Author(s): Takayoshi Katoh, Takeshi Yamamoto, Shigehiko Nishimura, Takeki Myoren, Wakako Murakami, Masakazu Fukuda, Makoto Ohno, Hiroki Tateishi, Mamoru Mochizuki, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Masafumi Yano
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京（東京国際フォーラム）
• [Presentation] Dantrolene May Suppress Arrhythmogenesis by Inhibition of CaMKII-mediated Aberrant Ca2+ Release Within the Ryanodine Receptor in Cardiac Troponin T-related Familial Hypertrophic Cardiomyopathy (2013)
  • Author(s): Shinichi Okuda, Masakazu Fukuda, Takayoshi Katoh, Shigehiko Nishimura, Shigeki Kobayashi, Takeshi Yamamoto, Masafumi Yano
  • Organizer: 86th Scientific Session of American Heart Association
  • Place of Presentation: Dallas(U. S. A)
  • Year and Date: 2013-11-16
• [Presentation] A Novel Selective EP4 Receptor Agonist Improves Intracellular Ca2+ Handling and Cardiomyocyte Function in Intact Failing Cardiomyocytes (2013)
  • Author(s): Wakako Murakami, Shigeki Kobayashi, Takeki Myoren, Shigehiko Nishimura, Takayoshi Katoh, Masakazu Fukuda, Makoto Ono, Hiroki Tateishi, Mamoru Mochizuki, Tetsuro Oda, Shinichi Okuda, Takeshi Yamamoto, Masafumi Yano
  • Organizer: 86th Scientific Session of American Heart Association
  • Place of Presentation: Dallas(U. S. A)
  • Year and Date: 2013-11-16
• [Presentation] Dantrolene Inhibits Aberrant Ca2+ Release and Arrhythmogenesis via Enhancing Binding of Calmodulin to RyR2 in CPVT-Associated Mutation (2013)
  • Author(s): Masakazu Fukuda, Takeshi Yamamoto, Shigehiko Nishimura, Takeki Myouren, Takayoshi Katoh, Wakako Murakami, Makoto Ono, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Masafumi Yano
  • Organizer: 86th Scientific Session of American Heart Association
  • Place of Presentation: Dallas(U. S. A)
  • Year and Date: 2013-11-16
• [Presentation] カテコラミン誘発性多形性心室頻拍関連の遺伝子変異を持つリアノジン受容体におけるカルモジュリンの効果について (2013)
  • Author(s): 福田昌和，山本 健，西村滋彦，明連武樹，加藤孝佳，村上和華子，大野 誠，小田哲郎，奥田真一，土居正浩，小林茂樹，矢野雅文
  • Organizer: 第61回日本心臓病学会学術集会
  • Place of Presentation: 熊本（ホテル日航熊本）
• [Presentation] 急性心不全におけるカテコラミン誘発性心筋傷害に対するカルペリチドの心筋保護効果についての検討 (2013)
  • Author(s): 村上和華子，小林茂樹，須佐建央，明連武樹，加藤孝佳，福田昌和，奥田真一，土居正浩，山本 健，矢野雅文
  • Organizer: 第61回日本心臓病学会学術集会
  • Place of Presentation: 熊本（ホテル日航熊本）
• [Presentation] Novel Selective EP4 Receptor Agonists Restore the Intracellular Ca2+ Handling and the Cardiomyocyte Function in Heart Failure (2013)
  • Author(s): Wakako Murakami, Shigeki Kobayashi, Takeki Myoren, Shigehiko Nishimura, Takayoshi Katoh, Masakazu Fukuda, Shinichi Okuda, Tetsuro Oda, Takeshi Yamamoto, Masafumi Yano
  • Organizer: 第17回日本心不全学会学術集会
  • Place of Presentation: 埼玉（大宮ソニックシティ）
• [Presentation] Dissociation of Calmodulin from RyR2 Plays a Key Role in Diastolic Ca2+ Leak from Sarcoplasmic Reticulum in Pressure-overload Heart Failur (2013)
  • Author(s): Takayoshi Katoh, Takeshi Yamamoto, Shigehiko Nishimura, Masakazu Fukuda, Makoto Ohno, Hiroki Tateishi, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Masafumi Yano
  • Organizer: 第17回日本心不全学会学術集会
  • Place of Presentation: 埼玉（大宮ソニックシティ）
• [Presentation] Dantrolene May Suppress Arrhythmogenesis by Inhibition of CaMKII-mediated Aberrant Ca2+ Release Within the Ryanodine Receptor in Cardiac Troponin T-related Familial Hypertrophic Cardiomyopathy (2013)
  • Author(s): Shinichi Okuda, Masakazu Fukuda, Takayoshi Katoh, Shigehiko Nishimura, Shigeki Kobayashi, Takeshi Yamamoto, Masafumi Yano
  • Organizer: 86th Scientific Session of American Heart Association
  • Place of Presentation: Dallas, TX, USA
• [Presentation] A Novel Selective EP4 Receptor Agonist Improves Intracellular Ca2+ Handling and Cardiomyocyte Function in Intact Failing Cardiomyocytes (2013)
  • Author(s): Wakako Murakami, Shigeki Kobayashi, Takeki Myoren, Shigehiko Nishimura, Takayoshi Katoh, Masakazu Fukuda, Makoto Ono, Hiroki Tateishi, Mamoru Mochizuki, Tetsuro Oda, Shinichi Okuda, Takeshi Yamamoto, Masafumi Yano
  • Organizer: 86th Scientific Session of American Heart Association
  • Place of Presentation: Dallas, TX
• [Presentation] Dantrolene Inhibits Aberrant Ca2+ Release and Arrhythmogenesis via Enhancing Binding of Calmodulin to RyR2 in CPVT-Associated Mutation (2013)
  • Author(s): Masakazu Fukuda, Takeshi Yamamoto, Shigehiko Nishimura, Takeki Myouren, Takayoshi Katoh, Wakako Murakami, Makoto Ono, Tetsuro Oda, Shinichi Okuda, Shigeki Kobayashi, Masafumi Yano
  • Organizer: 86th Scientific Session of American Heart Association
  • Place of Presentation: Dallas, TX, USA
• [Presentation] Fixing Ca2+ Leakage From Cardiac Ryanodine Receptor by Low-dose of β Blocker Safely Enhances Inotropic Response to Milrinone in Acute Heart Failure (2012)
  • Author(s): Shigeki Kobayashi, Wakako Murakami, Takayoshi Kato, Masakazu Fukuda, Akihiro Hino, Hiroki Tateishi, Takeshi Yamamoto, Takeshi Yamamoto, Masafumi Yano, Masunori Matsuzaki
  • Organizer: 85th Scientific Session of American Heart Association
  • Place of Presentation: Los Angeles(U. S. A)
  • Year and Date: 2012-11-03
• [Presentation] Urinary 8-hydroxy-2' -deoxyguanosine as a Novel Marker of Left Ventricular Remodelling in Patients With Dilated Cardiomyopathy (2012)
  • Author(s): Wakako Murakami, Shigeki Kobayashi, Takamasa Oda, Hiroki Tateishi, Tomoko Nao, Jutaro Yamada, Takayuki Okamura, Masafumi Yano, Masunori Matsuzaki
  • Organizer: 85th Scientific Session of American Heart Association
  • Place of Presentation: Los Angeles(U. S. A)
  • Year and Date: 2012-11-03
• [Presentation] Elevated Myocardial Oxidative Stress Induced by Catecholamines Related to Transient Left Ventricular Cysfunction in Patients With Takotsubo Cardiomyopathy (2012)
  • Author(s): Wakako Murakami, Shigeki Kobayashi, Tadamitsu Nakashima, Hiroki Tateishi, Shinichi Okuda, Masahiro Doi, Yasuaki Wada, Tomoko Nao, Jutaro Yamada, Takayuki Okamura, Masafumi Yano, Masunori Matsuzaki
  • Organizer: 85th Scientific Session of American Heart Association
  • Place of Presentation: Los Angeles(U. S. A)
  • Year and Date: 2012-11-03
• [Presentation] Urinary 8-hydroxy-2' -deoxyguanosine, An Oxidative Stress Marker, Predicts The Inflammatory Activity within the Heart in Patients with Cardiac Sarcoidosi (2012)
  • Author(s): Shigeki Kobayashi, Wakako Murakami, Seiko Fukuta, Masakazu Fukuda, Shinichi Okuda, Tomoko Nao, Masahiro Doi, Yasuaki Wada, Masafumi Yano, Masunori Matsuzaki
  • Organizer: 85th Scientific Session of American Heart Association
  • Place of Presentation: Los Angeles(U. S. A)
  • Year and Date: 2012-11-03
• [Presentation] Acceleration of the Early Diastolic Filing by Cardiac Re-synchronization is Important for Improving Symptoms of Severe Heart Failure (2012)
  • Author(s): Shigeki Kobayashi
  • Organizer: 85th Scientific Session of American Heart Association
  • Place of Presentation: Los Angeles, CA, USA
• [Presentation] Fixing Ca2+ Leakage From Cardiac Ryanodine Receptor by Low-dose of β Blocker Safely Enhances Inotropic Response to Milrinone in Acute Heart Failure (2012)
  • Author(s): Shinichi Okuda
  • Organizer: 85th Scientific Session of American Heart Association
  • Place of Presentation: Los Angeles, CA, USA
• [Presentation] Enhanced Binding of Calmodulin to RyR2 Inhibits Aberrant Ca2+ Release and Arrhythmogenesis in CPVT-Associated Mutation (2012)
  • Author(s): Masakazu Fukuda
  • Organizer: 85th Scientific Session of American Heart Association
  • Place of Presentation: Los Angeles, CA, USA
• [Presentation] Elevated Myocardial Oxidative Stress Induced by Catecholamines Related to Transient Left Ventricular Cysfunction in Patients With Takotsubo Cardiomyopathy (2012)
  • Author(s): Wakako Murakami
  • Organizer: 85th Scientific Session of American Heart Association
  • Place of Presentation: Los Angeles, CA, USA
• [Presentation] Urinary 8-hydroxy-2'-deoxyguanosine, An Oxidative Stress Marker, Predicts The Inflammatory Activity within the Heart in Patients with Cardiac Sarcoidosis (2012)
  • Author(s): Shigeki Kobayashi
  • Organizer: 85th Scientific Session of American Heart Association
  • Place of Presentation: Los Angeles, CA, USA
• [Presentation] Urinary 8-hydroxy-2'-deoxyguanosine as a Novel Marker of Left Ventricular Remodelling in Patients With Dilated Cardiomyopathy (2012)
  • Author(s): Wakako Murakami
  • Organizer: 85th Scientific Session of American Heart Association
  • Place of Presentation: Los Angeles, CA, USA
• [Presentation] Structure-Based Drug Design to Modulate RyR2 Function (2011)
  • Author(s): Masafumi Yano
  • Organizer: 84th American Heart Association Scientific Sessions
  • Place of Presentation: Orlando, FL, USA
  • Invited
• [Presentation] Mutation-linked Defective Domain Interaction within the Ryanodine Receptor Causes Ca2+ Leak Leading to Catecholaminergic Polymorphic Ventricular Tachycardia (2011)
  • Author(s): Takeshi Suetomi
  • Organizer: 84th American Heart Association Scientific Sessions
  • Place of Presentation: Orlando, FL, USA
• [Presentation] Correction of Defective Calmodulin Binding to Cardiac Ryanodine Receptor Inhibits Aberrant Ca2+ Release in CPVT-associated Mutation (2011)
  • Author(s): Masakazu Fukuda
  • Organizer: 84th American Heart Association Scientific Sessions
  • Place of Presentation: Orlando, FL, USA
• [Presentation] Low-dose of β blocker in combination with milrinone improve cardiac function in patients with acute decompensated heart failure (2011)
  • Author(s): Shigeki Kobayashi
  • Organizer: European Society of Cardiololgy Congress
  • Place of Presentation: Paris, France