プログラム・抄録集会長講演（PL）日本が創る心不全学の潮流 −実臨床と基礎医学の往還から− 国立循環器病研究センター臨床研究部・心臓血管内科医学は、基礎医学と臨床医学から成り立つが、その関係は、物理学と工学の関係とは異なり、基礎医学の成果を臨床医学に演繹することが難しい。それは、基礎医学が「生物学」に、臨床医学が「統計学」ということなった学問体系に立脚するからであると考えられる。とすると、臨床医学の発展は、臨床現場を原点に持つ必要があるのは自明である。実際、基礎医学の一つである薬理学・分子生物学などの研究は、降圧剤としてのβ遮断薬や ACE 阻害薬を臨床の場に生み出したが、心不全におけるβ遮断薬・ACE 阻害薬療法の実践は、臨床的観察を通して生み出された。しかし、臨床的観察から生み出された事実を実臨床に応用するためには、生物学のフィルターを通してその妥当性を精査する必要がある。つまり、よりよい医療を提供するためには、臨床において綿密な医療データベースを疫学の知識を導入して構築し、そこからのヒントを基礎医学に展開し、その成果を再度実臨床に戻す「基礎と臨床の往還」という作業を介して医薬品を開発し、大規模臨床研究において臨床的かつ科学的に検証するというパイプラインを創生することが重要である（図 1、図 2）。では、具体的にどうすればいいのか？我々は、さらに新しい心不全治療法を開発するため、臨床の場のヒントから、色々な試みを行っている。例えば、これまでヒトの不全心筋を採取して、その遺伝子発現解析行ってきた。心不全のマーカーである血中 BNP レベルや心機能と強い相関のある発現遺伝子をピックアップして解析すると、 MLCK3などの予期せぬ遺伝子が心不全と強いつながりがあることが明らかとなる。また、カルテなどの医療データに「データマイニング手法」を施行し、新しい薬剤の探索をおこなっている。その結果、1）ACEI・β遮断薬による心不全改善の検証に加え、2）ヒスタミン受容体遮断薬・糖尿病治療薬による心不全改善の可能性が示されている。これらの臨床の場から得られたヒントを、基礎医学に展開し、その成果を再度臨床の場に展開しつつある。つまり、心臓病・心不全の臨床を起点として、循環生理・薬理学や分子生物学などの基礎医学との往還、さらにその成果を大規模臨床研究において検証するというプロセスを通じて新しい循環器病学のパラダイムを創生すること大事であると考える。このようにして得られた成果は、薬剤介入大規模介入試験を行うことにより、通常治療の一つとして認められるようになってきた。しかし、このプロセスに 2 つの臨床的な問題が生じている。一つは、日本において、薬剤介入大規模介入試験は治験で行われることはほとんどない。日本の循環器病分野における大規模臨床研究は医者や製薬メーカ主導であり、その研究をいくら重ねても新たな適応をとることができず、大規模臨床研究と PMDA による治験との 2 元論が問題となっている。これを一元論にするためには、医師主導型治験を行うことが重要となるのである。もう一つの問題点は、大規模介入試験は、基礎研究の成果を、臨床医学の局面で、統計学的手法に基づいて判定するが、その結果は必ずしも各個人に当てはまらないということである。いわゆるテーラーメイド医療を行うための道筋を考える必要がある。この 2 つの問題をどうするかも今後真剣に考えていく必要がある。次世代型の心不全学は、心不全における臨床的に重要な課題について重点的に基礎研究を行い、それをいち早く臨床に還元し、その成果をおのおのの患者さんに役立てるための方策を考えることを目標としたいと考える。それが、心不全の患者さんを少しでも救う道ではないかと思う。 111 会長講演北風政史第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society 特別企画１（SS1）早期探索臨床試験拠点 MeDICI プロジェクトと心不全学会の合同シンポジウム SS1-1 MeDICIプロジェクトの概要峰松一夫国立循環器病研究センター病院特別企画早期・探索的臨床試験拠点整備事業は、新規薬物・機器の臨床試験拠点整備、日本発革新的医薬品・医療機器創出を目的とし、2011 年度に 5 機関が選定された。うち国立循環器病研究センター（国循）は唯一の医療機器開発（脳・心血管領域）を担当している。国内医療機器産業は大幅な輸入超過状態で、市場も医薬品の約 1/4 に過ぎない。その克服は喫緊の国家的課題である。我々は本事業を、ルネサンスを支えたメディチ家にたとえ、MeDICI Project （Medical Device Innovation Circumstances Improvement Project）と命名した。まず、研究所、病院、研究開発基盤センターが「三位一体」となってコンソーシアム委員会を組織し、事業進を管理している。人材を含めた各種体制整備（信頼性保証体制整備、国内アカデミア初の ISO13485 取得準備など）、シーズ選定委員会による有望医療機器シーズ公募・選定、積極的開発支援を行い、将来を見据えた各種教育研修、医療機器開発相談・支援窓口開設なども実施中である。支援 15 シーズの中には、既に上市され、良好な評判を得ているものもある。脳動脈瘤治療用カバードステントなどは、医師主導治験準備が進んでいる。 SS1-2 ハイリスク医療機器の開発マネジメント稲垣悦子独立行政法人国立循環器病研究センター研究開発基盤センターステント，人工心臓等、循環器領域で使用される治療用医療機器はいわゆるハイリスク医療機器に分類されるものが多い．医療における安全の意識が高まる昨今，医療機器開発においてもリスクを低減し，それをマネジメントすることが要求されている．医療機器開発マネジメントに関係する国際的な規格に『ISO13485：医療機器の品質マネジメントシステム』がある．本システムは設計開発を含む医療機器のライフサイクル全体をカバーするマネジメントシステムであり，各国の法規制にも導入されてきている．ISO13485 では製品ライフサイクル全体を通じてリスクマネジメントを行うことを規定しており，手法として『ISO14971：医療機器−リスクマネジメントの医療機器への適用』を引用している．リスクの高い医療機器は多様な技術を組み合わせた複雑な製品や，製品の使用される環境も複雑な場合が多い．そのような製品は開発の初期段階から系統化された手法で開発をマネジメントすることによって，開発における無駄，見落とし，後戻りを防止し，結果的に製品を早期に創出することになる．アカデミアにおける医療機器開発においてもこのような開発マネジメントが必要と考える． 112 プログラム・抄録集 SS1-3 アカデミアの医療機器開発ー人工臓器部の取り組み武輪能明、巽英介国立循環器病研究センター人工臓器部 SS1-4 A View of Regulation about Development of Medical Devices in Academic Institution Shuichi MOCHIZUKI Department of Clinical Study and Informatics, Center for Clinical Sciences, National Center for Global Health and Medicine Validating "clinical signiﬁcance of the medical devices on the market" is the most important as you want to buy and apply to your patients or your family. The Safety is the ﬁrst priority and it could evaluate only in non-clinical test in general. Non-clinical evaluation is very important in development. In Japan before starting clinical trials PMDA checked non-clinical data detail and ethical things as "30-days surveillance" on the Pharmaceutical Aﬀairs Act. In clinical trials regulation needs the objective evidence as evaluating the hypothesis of primary endpoint. Clinician have to consider about non-clinical evaluations, Engineers have to consider about clinical trials. The other high hazard to go to the Market is needs of "Marketing Approval Holder" for selling the medical devices. So we have to promote to companies. In early phase we have to make a good relationship with companies. However the devices is unprofitable, we found our own company and approve "Marketing Approval Holder". Academic mission for development of medical devices is developing the devices that is unprofitable for company, but have needs for patients. Only academic institutions could develop these Devices for unmet medical needs for pediatrics, for rare diseases（Orphan devices）, and so on. I think the public government funds should be injected for these developments. 113 特別企画国循は本邦の医療機器開発拠点として、研究所と病院が一体となり基礎研究から臨床応用へシームレスに開発を進める体制を整えている。その中で人工臓器部は、人工心臓や人工肺の他、様々な医療機器のシーズ発案から、大動物を用いた橋渡し研究等の部分を担ってきた。MeDICI プロジェクトでは、中核シーズの「Bridge-to-Decision を目的とした超小型補助循環システム」の開発を行っている。数種の体内埋込型補助人工心臓が使用可能な現在でも、高額な同機器を使用して長期間の補助が必要か判断を要する心不全症例が少なからず存在し、つなぎとして使用できる安価で抗血栓性の高い体外式遠心血液ポンプと送脱血管を組み合わせた補助循環システムの早期製品化を目指している。その他にも MeDICI プロジェクト 13 シーズのうち 3 つに携わっており、中には小児補助循環等の臨床での必要性は高いが利益性に乏しく、企業が躊躇する様な案件も含まれており、アカデミアで医療機器開発を行う重要な意義も示している。また一方で、品質管理の国際認証基準を取得するべく体制を整えており、信頼性のある医療機器を世界に滞りなく製品化する事にも務めている。第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society 特別企画２（SS2）日本・台湾心不全学会（Japan/Taiwan）合同セッション SS2-1 The Role of MicroRNA-208a and Endoglin in Myocardial Fibrosis Kou-Gi SHYU Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan 特別企画 Cardiac ﬁbrosis is closely associated with heart failure because cardiac ﬁbrosis may cause the loss of normal cardiac function. Endoglin is a homeodimeric membrane glycoprotein that is a co-receptor of transforming growth factor-β1（TGF-β1）and β3. Endoglin is a potent mediator of profibrotic effects of angiotensin II on cardiac fibroblasts and can modulate the effect of TGF-β1 on extracellular matrix synthesis. These data indicate that endoglin plays an important role in fibrogenesis in cardiac remodeling. Endoglin induced by is TGF-β1 is largely through PI-3 kinase, Akt, Smad3/4 and endoglin promoter pathways. A microRNA（miR） small, 22-nucleotide non-protein-coding RNA that inhibits transcription or translation by interacting with the 3 untranslated regions of target mRNA and promoting target mRNA degradation（gene silencing）. Recently, MiR has been shown to induce gene expression. Because of their capability to monitor the expression levels of the genes that control both adaptive and maladaptive cardiac remodeling processes, miRs may be vitally involved in the pathogenesis of heart failure. Mir-208a seems to be fundamental for the expression of genes involved in cardiac ﬁbrosis and hypertrophic growth. Mir-208a is upregulated in pressure overloading with thoracic aortic banding and is activated by mechanical stress. Cyclic mechanical stretch enhances miR208a expression in cultured rat cardiac myoblasts. The stretch-induced miR208a is mediated by TGF-β1. Mir208a activates endoglin expression and may result in cardiac ﬁbrosis. Mir-208a can increase endoglin expression in cardiac myoblast. Mir-208a increases endoglin expression to induce myocardial ﬁbrosis in volume overloaded heart failure. Treatment with atorvastatin can attenuate the myocardial ﬁbrosis induced by volume overload through inhibition of endoglin expression. SS2-2 Sudden Cardiac Arrest: Focusing on the Unsolved Problems Wen-Jone CHEN1,2） Department of Internal Medicine (Cardiology) and Emergency Medicine, National Taiwan University, Taipei, Taiwan、 Superintendent, Lo-tung Poh-ai Hospital, Yilan County, Taiwan 1） 2） Cardiovascular disease is a leading cause of global mortality, and it is estimated that about 45% to 50% of them are due to sudden cardiac death. For out-of-hospital cardiac arrest（OCHA）, the survival to discharge rate ranged from 3% to 16%, and if we limited the study population to the victims of VT/VF, the survival rate ranged from 10% to 40%. In the past 10 years, we noted the increasing by-stander CPR rate, more frequent automated external deﬁbrillator（AED）use and increased survival rate. However, the results are still suboptimal, and more research should be done before we can improve the survival of sudden cardiac arrest victims. In this special lecture, I would like to introduce the current status of sudden cardiac arrest in Taiwan and discuss several important unsolved issues of sudden cardiac arres. These issues include: 1. Adrenaline use for cardiac arrest. 2. New deﬁbrillation method for VF. 3. Use of Extracoporeal Membrane Oxygenation in refractory cardiac arrest. 4. Optimizing oxygenation and hemodynamics after return of spontaneous circulation. 5. Management of post-cardiac arrest syndrome. ＊ Therapeutic hypothermia ＊ Pharmacological interventions including steroid, erythropoietin, propofal, cyclosporine, xenon, …etc. 114 プログラム・抄録集 SS2-3 A Critical Role of Senescence-induced Inﬂammation in Cardiovascular Disease Tohru MINAMINO Department of Cardiovascular Biology and Medicine Niigata University Graduate School of Medical and Dental Sciences SS2-4 Global and Regional Left Ventricular Dysfunction Relates to Insulin Resistance in Patients with Aortic Valve Sclerosis Yasuki KIHARA、Hiroto UTSUNOMIYA、Takayuki HIDAKA、Eiji KUNITA、 Hideya YAMAMOTO Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences BACKGROUND: In patients with aortic valve sclerosis（AVS） , the pathogenesis of subclinical impairment of LV function is not fully elucidated. METHODS: We studied 57 patients（70±8 y.o.）with asymptomatic AVS and normal LV ejection fraction. LV longitudinal and circumferential strain and strain rate were analyzed using two-dimensional speckle tracking echocardiography. They were divided into the insulin-resistant group （AVS+IR）and no insulin-resistant group（AVS-IR）according to the median value of HOMA-IR. Computed tomography scans were also performed to measure the aortic valve calcium score and the visceral adipose tissue（VAT）area. Age- and sex-adjusted control subjects were recruited for the comparison. RESULTS: There were no signiﬁcant diﬀerences in LV ejection fraction or mass index among the groups. The AVS+IR group had a higher aortic valve calcium score and a larger VAT area than the AVS-IR group. LV global , and early diastolic SR were signiﬁcantly lower in the AVS+IR group than longitudinal strain, strain rate（SR） in the AVS-IR and control groups, whereas circumferential functions were not signiﬁcantly diﬀerent. Multiple linear regression analyses revealed insulin resistance as an independent determinant of LV longitudinal strain, SR, and early diastolic SR regardless of LV mass index or VAT area. CONCLUSIONS: Insulin resistance is an independent predictor of subclinical LV dysfunction regardless of concomitant visceral obesity and LV hypertrophy. [PMID: 24767168] 115 特別企画 Epidemiological studies have shown that age is the dominant risk factor for lifestyle-related diseases. The incidence and the prevalence of heart failure, coronary heart disease and hypertension increase with advancing age. However, the molecular mechanisms underlying the increased risk of such diseases that is conferred by aging remain unclear. Cellular senescence is originally described as the ﬁnite replicative lifespan of human somatic cells in culture. Cellular senescence is accompanied by a speciﬁc set of phenotypic changes in morphology and gene expression including negative regulators of the cell cycle such as p53. Primary cultured cells from patients with premature aging syndromes are known to have a shorter lifespan than cells from age-matched healthy persons. It is also reported that the number of senescent cells increases in various tissues with advancing age. I therefore hypothesize that cellular senescence in vivo contributes to the pathogenesis of age-associated disease. An important feature shared by several types of senescent cells is persistent up-regulation of inﬂammatory molecules and accumulating evidence has suggested a critical role of senescence-induced inﬂammation in metabolic and cardiovascular disease. Here I will present our recent data on the role of cellular senescence in age-related pathologies and will discuss the potential of anti-senescence as a novel therapeutic strategy for age-associated diseases. 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society 特別企画３（SS3）アジアセッション SS3-1 Clinical Experience of Cardiac Rehabilitation and Heart Failure Clinic: Multidisciplinary Team Approach Seok-Min KANG Cardiology Division, Severance Cardiovascular Hospital, College of Medicine, Yonsei University 特別企画 Heart failure（HF）is a clinical syndrome connected with cardiovascular（CV）system as well as other organs , consisting of exercise and skeletal muscles. In lines of evidences with the above, cardiac rehabilitation（CR） training, CV risk management, low salt diet, medication education, and etc aims at recovery of physical, social and psychic function. According to 2013 ACCF/AHA HF guideline, exercise training is Class I and cardiac rehabilitation is Class IIa for HF patients. Evidence has shown that exercise training in HF patients, both aerobic and resistance, can increase peak oxygen consumption and exercise capacity, improve NYHA functional class, reduce mortality and improve the quality of life. Exercise training can improve skeletal muscle metabolism, increase blood ﬂow within the skeletal muscles, increase capillary density, promote the synthesis and release of nitric oxide, improve angiogenesis, and decrease oxidative stress. Exercise reduces sympathetic activity and increases parasympathetic activity, thus reducing arrhythmia and angina. This presentation will introduce the experience of HF clinic for the management of HF patients in our institute. In addition, we also have monthly HF joint meeting with heart rhythm（HR）team to improve the management of device therapy for HF patients. This presentation will focus on multidisciplinary team approach consisting of HF specialists, HR specialists, dietitian, CR nurse, and certificated clinical exercise specialists in HF management. SS3-2 Dose-Dependent Cardiac Electromechanical Disturbances in Chronic Alcohol Users Hung-I YEH、Chung-Lieh HUNG、Yu-Jun LAI Mackay Memorial Hospital, Mackay Medical College, New Taipei city, Taiwan Background: We examined the association between the amount of ethanol consumption and the cardiac electromechanical properties in people without overt alcoholic cardiomyopathy and explored the underlying mechanisms. Methods and results: We analyzed subjects undergoing annual health survey and categorized them into 3 groups （<1 drink, >=1 drink per week or daily use）. Dose-responsive LV dilation, wall thickness, impaired LV diastolic function together with attenuated LV and LA longitudinal strains, and LA diastolic strain rate were observed, even after propensity matching for key clinical variables, medical histories and life styles. In parallel, we examined community-dwelling participants with high prevalence of habitual alcohol intake and found those with heavy consumption（>90 g/day）showed markedly widened QRS duration and prolonged QT interval. C57BL/6 mice fed chronic alcohol diet for 14 weeks demonstrated impaired ventricular systole, reduced intraventricular conduction, slower action potential upstroke velocity, and decreased resting membrane potential, with down-regulated Cx43 gap junction, up-regulated but clustered Nav1.5 sodium channel, and increased collagen I expression in the ventricle as well as attenuated response of ventricular conduction to gap junction blocker heptanol and sodium channer blocker tetrodotoxin. Conclusion: Chronic alcohol ingestion in humans is associated with dose-dependent electromechanical disturbances, which can be recapitulated in mice fed chronic alcohol diet. The mechanisms underlying intraventricular conduction disturbances involved suppressed gap junction and sodium channel plus ﬁbrosis. 116 プログラム・抄録集 SS3-3 Heart Failure with Preserved Ejection Fraction（HFPEF）: From Diagnosis to Management Cheuk-Man YU1,2） Department of Medicine & Therapeutics, Prince of Wales Hospital; Institute of Vascular Medicine, Li Ka Shing Institute of Health & Science, Faculty of Medicine、 The Chinese University of Hong Kong 1） 2） The prognosis of HFREF appears to be better than that of HF with reduced ejection fraction, in particular when compared the two conditions in a metaanalysis. This is compatible with our clinical observation. For the treatment of HFPEF, a range of medications had been evaluated in randomized, controlled clinical trials. These include diuretics, beta-blocker, digoxin, ACEI and angiotensin receptor blocker. The eﬃcacy of these drugs will be discussed in the lecture. Of note, no treatment has yet been shown convincingly to reduce morbidity and mortality in patients with HFPEF to date. More studies are warranted to understand the pathophysiology and management of HFPEF. SS3-4 Current Perspectives of Therapeutic Strategy for Advanced Heart Failure in Japan Koichiro KINUGAWA The Department of Therapeutic Strategy for Heart Failure, The University of Tokyo, Tokyo, Japan Japanese standard is not universally common in terms of device usage as well as pharmacological therapy for heart failure. Advanced heart failure needs multidisciplinary approach, but available options are sometimes limited in Japan. For example, the annual number of heart transplantation is approximately 40 over the whole country, nevertheless destination therapy with implantable ventricular assist device has not been allowed by the government insurance system. On the other hand, a newly developed aquaretic agent can be used under wider indication compared with other countries. In such a circumstance, we have developed a multidisciplinary team for advanced heart failure. I would like to present our current status and future perspectives. 117 特別企画 Heart failure（HF）with preserved ejection fraction（HFPEF）is a disease of global burden. It is particularly common among patients with hypertension, advanced age, though with hypertrophic condition of the left ventricle, and also female gender. In Hong Kong, our experience showed that HFPEF comprised more than half of patients admitted to the hospital for HF. The diagnosis of HFPEF also deserves more attention, as it will be aﬀected by the value of ejection fraction being used. The use of echocardiography becomes an essential tool in the diagnosis of this condition, as not only a relatively normal ejection fraction shall be present, but also the demonstration of left ventricular diastolic dysfunction is needed. Furthermore, our study showed that subclinical systolic dysfunction is present in up to half of patients with HFPEF when assessed by tissue Doppler echocardiography. 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society SS3-5 Mechanistic Basis for Diabetic Cardiomyopathy Ichiro SHIOJIMA Department of Medicine II, Kansai Medical University 特別企画 Patients with diabetes mellitus continue to increase in number and diabetes is one of the major risk factors for cardiovascular diseases. In addition, it is also recognized that the risk for heart failure is increased in diabetic patients even in the absence of overt myocardial ischemia or hypertension or other risk factors for heart failure. This diabetes-associated ischemia-independent heart pathology is called diabetic cardiomyopathy. However, the mechanism by which diabetes promotes the development of heart failure is not clearly deﬁned. Because type II diabetes is associated with insulin resistance or impaired insulin signaling in multiple organs including the heart, it was hypothesized that myocardial insulin resistance is implicated in the pathogenesis of diabetic cardiomyopathy. In order to test this hypothesis, insulin receptor gene was deleted in the adult cardiomyocytes in an inducible manner. Inducible cardiac-speciﬁc insulin receptor gene deletion resulted in progressive decline in contractile function and increased interstitial ﬁbrosis. These observations suggest the requirement of myocardial insulin signaling for the maintenance of contractile function in the adult heart and support the notion that myocardial insulin resistance plays a causal role in diabetic cardiomyopathy. 118 プログラム・抄録集特別企画４（SS4）症例から学ぶ心不全の既知と未知：U40 心不全ネットワーク SS4-1 Left Ventricular Outﬂow Tract Obstruction Caused by Massive Mitral Annular Calciﬁcation in the Patient with Hypertrophic Cardiomyopathy Naofumi YOSHIDA、Tatsuya MIYOSHI、Taira NINOMARU、 Yuichi NAGAMATSU、Naoki TAMADA、Noritoshi HIRANUMA、 Yoshihiro SASAKI、Gaku KANDA、Noriyasu KOBAYASHI、Takashi FUJII Department of Cardiology, Ako city hospital SS4-2 Extreme Left Ventricular Hypertrophy with Acute Myocardial Infarctionreconsider The Diagnosis and Mechanism of Ischemia Norio SUZUKI、Keisuke KIDA、Ryo KAMIJIMA、Masaki IZUMO、 Kihei YONEYAMA、Kengo SUZUKI、Yoshihiro J AKASHI、Tomoo HARADA Department of Cardiology, St. Marianna University School of Medicine, Kawasaki, Japan Left ventricular hypertrophy is often identifiable in the clinical setting, although the definitive diagnoses cannot be made in several cases. This case report presents a 76-year-old woman who complained chest pain and general prostration. Electrocardiography recorded by her primary doctor showed ST elevation in leads II, aVF, V4 to V6; the patient was suspected acute coronary syndrome and transferred to the emergency department in our hospital. Echocardiography at arrival showed the marked left ventricular diffuse hypertrophy and akinetic wall motion at the lateral wall of the left ventricle. The present case provided us an opportunity to reconsider the diagnosis and mechanism of ischemia; therefore, we would like to review and discuss this case with U40 heart failure network members and supporters. 119 特別企画 An 83-year-old woman was admitted to our hospital because of exertional dyspnea and palpitation. She had a history of heart failure and received medications for hypertrophic cardiomyopathy（HCM）and mild left ventricular outflow tract（LVOT）obstruction in five years. Her symptoms were exacerbated by exertion, though she had no symptom at rest. Transthoracic echocardiography on admission showed ventricular septal hypertrophy, massive mitral annular calcification（MAC）and LVOT obstruction with a peak gradient of 15.4 mmHg at rest. Systolic anterior motion of mitral leaﬂet and mitral regurgitation were not documented. Additionally, the LVOT gradient in stress condition was evaluated and resulted in increased LVOT gradient （47.3 mmHg）with chest discomfort at 20 μg/kg/min dobutamine administration with Valsalva maneuver. Mitral stenosis was mild evaluated by catheter-based data and Gorlin equation（MVA 2.4 mm2）.We diagnosed latent hypertrophic obstructive cardiomyopathy（HOCM）with anterior displacement of mitral coaptation due to posterior MAC. Her symptom could not well controlled by medication, and finally we performed septal myectomy and mitral valve replacement because we considered that anterior displacement of mitral coaptation due to posterior MAC exacerbated dynamic LVOT obstruction and aggravated her symptoms. There might be some options to manage this patient. In this session, we would like to discuss how to evaluate pathophysiological eﬀect of MAC and the optimal management of this patient. 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society 特別企画５（SS5）心筋症 2014 - 臨床・研究の最前線日本心筋症研究会発足に向けて SS5-1 Genetic Etiology of Hypertrophic Cardiomyopathy Hiroyuki MORITA Department of Translational Research for Healthcare and Clinical Science, The University of Tokyo, Tokyo, Japan 特別企画 Clarifying the genetic etiology and pathophysiology of hypertrophic cardiomyopathy（HCM）, we could identify the molecular pathways how cardiac hypertrophy occurs, the mechanistic process how heart fails, consequently the specific targets for rational therapy. In a clinical setting, the genomic testing of HCMcausing mutation can help us establish the diagnosis for HCM patients, as well as assess the aﬀection status for their family members. Although sarcomere protein gene mutations are established as HCM-causing ones, the accumulated knowledge in genomic research arena is not yet applied into routine cardiovascular practice. Actually, there are some limitations that retard clinical application of substantial genetic ﬁndings. First, in half of the HCM cases, especially sporadic cases, causing-mutation is undeﬁned. Secondly, the same mutation could not necessarily induce the same clinical manifestation, making it difficult to establish the genotypephenotype correlation. In addition, it remains unclear how preclinical mutation carriers should be medically managed. Newly-developed high-throughput sequencing has enabled us to detect a variety of rare variants, therefore, we need to have the pipeline and database for contriving to ﬁlter out unrelated variants and work our way to a true causing mutation. In this presentation, HCM-causing mutations and their consequences in the pathogenesis of HCM will be summarized, and then, the perspectives of genomic diagnosis of HCM in a clinical practice will be discussed. SS5-2 Clinical Concept of Hypertrophic Cardiomyopathy in Current Euro/USA Management Guideline, and Progress of Septal Reduction Therapy Morimasa TAKAYAMA Department of Cardiology, Sakakibara Heart Institute Clinical concept of hypertrophic cardiomyopathy（HCM）has been expanded recently following to ACCF/ AHA 2011 guideline and latest ESC HCM 2014 guideline furthermore. The characteristic feature of HCM is well-known as sarcomere gene-mutation mediated disorder which presents asymmetric septal hypertrophy of ventricle. Clinical significant incidence of sudden cardiac death especially in young and diastolic heart failure often limits patient s quality of life. As causative gene analysis has progressed so far, clinical research and management has been developing such as hypertrophy imaging with MRI and CT, prevention of sudden death with implantable cardioverter deﬁbrillater, and septal reduction therapy surgically or percutaneously. The above two guidelines emphasize importance of institution with centerized clinical service in wide range of diagnosis and treatment experience together with longitudinal follow-up. Current policy of management with recommendation for HCM will be showed and discussed. 120 プログラム・抄録集 SS5-3 Deterioration of Cardiac Function During The Progression of Cardiac Sarcoidosis Fumio TERASAKI1）、Nobukazu ISHIZAKA2） Medical Education Center, Faculty of Medicine, Osaka Medical College, Takatsuki, Japan、 Department of Cardiology, Osaka Medical College, Takatsuki, Japan 1） 2） SS5-4 Arrhythmogenic Right Ventricular Cardiomyopathy Akihiko NOGAMI The Cardiovascular Division, University of Tsukuba, Tsukuba, Ibaraki Arrhythmogenic right ventricular cardiomyopathy（ARVC）is an inherited cardiomyopathy characterized by ventricular arrhythmias, increased risk of sudden death, and structural and functional abnormalities of right ventricle（RV）. The histopathologic finding of ARVC includes myocardial cell loss with fibrofatty replacement of RV muscle. In most cases, ARVC is inherited in an autosomal dominant pattern. Mutations in the most desmosomal proteins（plakophilin-2, desmoglein-2, and others）and in some nondesmosomal proteins （transforming growth factor-beta3, cardiac ryanodine receptor, and others）have been identiﬁed. Because of signiﬁcant heterogeneity in its manifestation, the diagnosis of ARVC is challenging and requires a multifaceted approach. The Task Force criteria were revised to increase sensitivity in 2010. Antiarrhythmic drug, especially with beta-blockers, sotalol, or amiodarone, is often effective in controlling the arrhythmias. Implantable cardioverter-deﬁbrillator signiﬁcantly reduced mortality in patients with high risk of sudden death. Although successful catheter ablation is feasible, long-term recurrence is common, probably because of its progressive nature. Recently, some investigators reported the usefulness of substratebased mapping. They suggested that the isolated delayed potentials during sinus rhythm were related to the ventricular arrhythmias and could be the target for the ablation. However, the endpoint of ablation, other than non-inducibility, remains undetermined. To reduce the development of ARVC, beta-blockers, preload-reducing （especially endurance ones） , are recommended. therapies, and the limitation of the competitive sports 121 特別企画 Recently, diagnosis, therapy, as well as understanding of the mechanism of pathogenesis of cardiac sarcoidosis have been markedly improved. It should be noted that decline in the cardiac systolic function may progress during a relatively short period of time, within a couple of months for example, in patients with systemic sarcoidosis. Abnormality in the conduction system or cardiac rhythms, which might reﬂect myocardial granuloma formation, may precede cardiac dysfunction. Certain biomarkers（ high-sensitive cardiac troponins）are associated with left ventricular dysfunction, thus, inflammatory cytokines may play an important role in the progression of cardiomyopathy. Nowadays, 18F-FDG PET and contrast enhanced cardiac magnetic resonance（CMR）imaging give clue to the diagnosis of cardiac sarcoidosis. The older technique, endomyocardial biopsy is still on active duty, it may directly prove the sarcoid lesion formation in the heart; however, this conventional diagnostic method is not sensitive enough in most of the time. We are thus confronting three questions:（1）when cardiac sarcoidosis involvement is suggested by imaging modalities, can we diagnose these patients with cardiac sarcoidosis even without histological confirmation;（2）can we start therapies for such patients diagnosed with suspected cardiac sarcoidosis without conﬁrmation by the histology?;（3）If so, when?To determine the most appropriate approach for the diagnosis and treatment of cardiac sarcoidosis, these points will warrant thorough prospective investigations. 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society SS5-5 Dilated Cardiomyopathy-Pathogenesis and Diagnosis Takayuki INOMATA Department of Cardiovascular Medicine, Kitasato University School of Medicine, Sagamihara, Japan 特別企画 Idiopathic dilated cardiomyopathy（IDCM）is an organic myocardial disease characterized by left ventricular cavity enlargement and impaired contractility in the absence of speciﬁc cardiac diseases including coronary artery diseases. Left ventricular（LV）remodeling is a major pathogenic process in the progression of heart failure and a confirmed predictor of future cardiac events. The inverse process, LV reverse remodeling （LVRR）,has been recognized in various degree derived after the introduction of neurohormonal agents such as beta-blockers or device therapy, indicating the heterogeneity of not only the disease severity but also its pathogenesis. Of 254 consecutive patients diagnosed in 1996-2011 with IDCM in our institute, excluding patients with reversible CM such as tachycardia- or endocrine-induced, normalization was achieved in 67 （33%）patients. Multivariate logistic regression analysis indicated that normalization is observed more often and earlier in patients with a preceding AHF episode than in those without. This fact indicates the functional or reversible process may contribute to the pathogenesis of this disease entity. In order to ﬁght against this disorder with a clinical eﬃciency, we must once leave only for the diﬀerential diagnosis presently deﬁned as IDCM and come back sincerely to observe the clinical phenotype seen in real-world practice. SS5-6 Problems that Needs to be Solved in Dilated Cardiomyopathy Yasushi SAKATA Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine Dilated cardiomyopathy（DCM）is the most common cardiomyopathy and its definition is enlargement of one or both of the ventricles and systolic dysfunction. Therapeutic strategy of DCM has been established by many clinical trials. The patients with DCM undergo mandatory inhibition of activated neurohumoral factors, administration of diuretics and inotropes, repair of structural and electrophysiological abnormality, and implantation of ventricular assist device（VAD）if necessary. However, the prognosis of DCM has not fully satisﬁed yet. There are at least two problems to be solved to improve the prognosis of DCM. One is to clarify the cause of DCM. No etiology can be found in about ﬁfty percent of DCM, and this is called as idiopathic DCM（iDCM）. Viruses and gene mutations are now recognized to be relatively common among patients with iDCM. However, the causality is still unknown. Disease-specific therapy would usually be expected for improvement of its prognosis. The other is to predict the reversibility of ventricular dysfunction. Some reversible forms of DCM are observed in hypertensive, peripartum, alcoholic, tachycardic and even idiopathic cardiomyopathy. However, no biomarker to predict reversible myocardium has used in clinical settings. The quantitative marker would be useful to determine the rapid and proper implication of VAD. 122 プログラム・抄録集 SS5-7 Cardiac MRI in Cardiomyopathy Hajime SAKUMA Department of Radiology, Mie University Hospital 123 特別企画 Cardiac magnetic resonance（CMR）plays a pivotal role in managing patients with heart failure and those with cardiomyopathies. CMR is recognized as the most accurate and reproducible method to assess regional and global myocardial function as well as morphology of the heart. In addition, late gadolinium enhanced （LGE） MRI permits detection of subendocardial myocardial infarction in patients with coronary artery disease （CAD）and myocardial ﬁbrosis in cardiomyopathies. LGE MRI is useful for classifying patients with heart failure in relation to the presence or absence of underlying CAD. Most heart failure patients with CAD had （DCM） had subendocardial or transmural enhancement, while majority of patients with dilated cardiomyopathy no LGE or mid-wall fibrosis. Therefore, CMR can be used as an effective and noninvasive gatekeeper in determining the etiology of heart failure. In patients with DCM, the presence of LGE is strongly associated with increased risk of adverse events, indicating the importance of CMR for risk stratification of DCM patients. One of the limitations of LGE MRI is a difficulty in assessing diffuse myocardial fibrosis. T1 mapping using MOLLI and other MR approaches can provide quantification of T1 relaxation time. By measuring pre- and post-contrast blood and myocardial T1, the extra-cellular volume（ECV）fraction of myocardial tissue can be quantiﬁed in vivo. This approach allows for non-invasive calculation of ECV which correlates with myocardial ﬁbrosis in patients with DCM. Quantiﬁcation of myocardial pre-contrast T1 time and ECV will have substantial impact in tissue characterization of cardiomyopathies. 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society 特別講演１（SL1） Heart Failure in Korea : Current Status and Future Challenges Myeong-Chan CHO1,2） President, The Korean Society of Heart Failure、 Professor, Department of Cardiology, Chungbuk National University Hospital 1） 2）特別講演特別講演２（SL2） The Quest for the Adult Cardiac Stem Cell Michael D. SCHNEIDER Imperial College London Cardiac progenitor/stem cells in adult hearts are a potential mode of self-repair, therapeutic product, and （inter） -relationships among reported cells remain obscure. Using single-cell target for activation in situ, though qRT-PCR and clonal analyses, we deﬁne four sub-populations in adult mouse myocardium sharing stem cell , antigen-1 （Sca1）,based on side population（SP）phenotype, platelet/endothelial cell adhesion molecule 1（CD31）（PDGFRα）. SP status predicted clonogenicity plus cardiogenic and platelet derived growth factor receptor-α , properties segregating more speciﬁcally to PDGFRα+ cells. PDGFR gene expression （Gata4/6, Hand2, Tbx5/20 ） α cells were characterized, instead, by Kdr/Flk1, Cdh5 , CD31 and lack of clone formation under identical conditions. Clonal progeny of single Sca1+ SP cells showed tri-lineage potential（cardiomyocyte, endothelial, smooth muscle）after cardiac grafting. LV ejection fraction and infarct size were both improved. However, the very low prevalence of long-term engraftment suggests early paracrine eﬀects, not diﬀerentiation, as the key mechanism for beneﬁts observed under these conditions. By fate-mapping, PDGFRα+/CD31- cells derived from cells formerly expressing Mesp1, Nkx2-5, Isl1, Gata5 and Wt1 , distinct from PDGFRα-/CD31+ cells（Gata5 low; Flk1, Tie2 high） . Thus, PDGFRα demarcates the clonogenic cardiogenic Sca1+ stem cell. 124 プログラム・抄録集特別講演３（SL3） Newest Highlights and Challenges in Heart Failure Therapy Michele HAMILTON Cedars Sinai Heart Medical Center 特別講演４（SL4） Mechanical Circulatory Support for End Stage Heart Failure Andrew BOYLE Cleveland Clinic Florida, USA Mechanical Circulatory Support has become part of the standard of care for the management of end-stage heart failure, particularly in countries with limited organ donors such as Japan. Progress has been made on the technology front but adverse events remain too high. Adverse events can be related to the technology itself, the patient s co-morbidities, patient management issues, and patient compliance. A thorough discussion on the indications and contraindications for MCS as well as common adverse events will be discussed. Also, a discussion on patient selection criteria will be had as the success of an MCS program is far more dependent on the selection and management of patients that it is on the type of VAD that is implanted. 125 特別講演 There have been many advances in heart failure management across the ﬁelds of medical therapy, mechanical interventions, and transplantation. New medications in the pipeline include hemodynamically-oriented therapies such as seralaxin, funny Ca-channel inhibitors slowing heart rate（ivradibine）, and most recently, encouraging results with neprilysin inhibition. Percutaneous interventions for aortic stenosis and mitral regurgitation are being investigated in multiple heart failure populations. Advanced mechanical support devices as both bridges and destination therapies are becoming smaller and more eﬀective. In transplantation, new therapies to reduce preformed antibodies and less invasive approaches to detecting rejection are leading to greater access to transplantation for sensitized patients and reduced costs and improved quality of life for many. Important challenges remain in heart failure therapy, especially in the area of coordination of global heart failure care. Evidence based, guideline-directed therapies including cardioprotective medications, resynchronization therapy and deﬁbrillators have certainly had substantial impact; however, we still have rapidly increasing numbers of heart failure patients and unsustainable costs. Addressing this requires increasing focus on integration of inpatient and outpatient care. Identification of the optimal utilization of hemodynamic and electrographic information generated by patients electronic devices will be important in this endeavor. Multidisciplinary programs including inpatient heart failure units, outpatient diuresis programs, and integration of palliative care will likely also improve outcomes in heart failure care. 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society 特別講演５（SL5） Addressing Cardiac Fibrosis: The Good, the Bad, and the Ugly Thomas FORCE、Hind LAL、Firdos AHMAD Vanderbilt University School of Medicine Fibrotic remodeling post MI is a critical problem in caring for patients. Herein we will explore strategies to limit post-MI ﬁbrosis. We will discuss mechanisms and approaches to limiting ﬁbrosis, including employing small molecule modulators of the ﬁbrotic response. 特別講演特別講演６（SL6）未知の循環調節ペプチドへの挑戦寒川賢治国立循環器病研究センター研究所心血管系は、多くの因子による複雑かつ巧妙な情報伝達および機能調節によって維持されており、その破綻が種々の疾患の発症等に繋がる。未知のペプチドの探索は容易ではないが、その発見は大きな breakthrough に繋がる。ナトリウム利尿ペプチド・ファミリー（ANP：1984 年 , BNP：1988 年 , CNP：1990 年）やアドレノメデュリン（1993 年）などの発見はその例と言える。その後 1999 年に胃組織から発見されグレリンは、強力な成長ホルモン（GH）分泌促進作用と共に摂食促進作用を有する。胃の内分泌細胞から分泌されたグレリンは、迷走神経求心路を介して中枢へのシグナル伝達に働く。また近年、交感神経抑制による血管拡張や不整脈の抑制など心血管系の保護など、循環器系における機能も明らかになっている。一方、ANP は発見されてから今年で30年になるが、最近 ANP の持つ新たな機能が明らかになってきた。それは私が 20 年ほど前から抱いていた、「なぜ、がんは心臓に転移しないのか？」という疑問が解明されたものであり、ANP の新たな機能としてのがん転移抑制作用である。本講演では、私の 35 年間にわたる未知のペプチドへの挑戦の概要を紹介したい。 126 プログラム・抄録集特別講演７（SL7） Heart Failure with Preserved Ejection Fraction : A Clinical Dilemna Michel KOMAJDA Cardiology University Pierre et Marie Curie-IHU/ICAN, Paris, France 特別講演８（SL8） The Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial（PARADIGMHF） John MCMURRAY Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow The Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortailty and morbidity in Heart Failure trial（PARADIGM-HF）compared LCZ696 to enalapril in patients with heart failure and reduced left ventricular ejection fraction（HF-REF）. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin（neutral endopeptidase）inhibitors（ARNIs）, which both block the renin angiotensin system and augment natriuretic peptides and other endogenous vasodilators. Patients with chronic HF, NYHA class II-IV symptoms, an elevated plasma BNP or NT-proBNP level, and an LVEF of 40% were enrolled. Patients entered a single-blind enalapril run-in period（titrated to 10 mg b.i.d.）, followed by an LCZ696 run-in period（100 mg titrated to 200 mg b.i.d.）.A total of 8442 patients tolerating both periods were randomized 1:1 to either enalapril 10 mg b.i.d. or LCZ696 200 mg b.i.d. The primary outcome was the composite of cardiovascular death or HF hospitalization, although the trial was powered to detect a15% relative risk reduction in cardiovascular death. The study was stopped early for beneﬁt after a median follow-up of 27 months. At baseline, 93% of patients were treated with a beta-blocker and 56% with a mineralocorticoid receptor antagonist. Compared with enalapril （mean±SD dose taken = 18.9±3.4 mg）, LCZ reduced the occurrence of the primary composite outcome and cardiovascular death. The full results will be presented and published at the European Society of Cardiology Congress 31 August 2014 and published simultaneously. The main ﬁndings plus additional outcomes and new analyses will be presented at the 18th Annual Scientiﬁc Meeting of the Japanese Heart Failure Society. 127 特別講演 Heart failure with preserved ejection fraction（HFpEF）is now recognized as a major and growing public health problem worldwide. Yet significant uncertainties still surround its pathophysiology and treatment, leaving clinicians in a dilemma regarding its optimal management. Whether HFpEF and Heart Failure with Reduced Ejection Fraction（HFrEF）are two distinct entities or two ends of a common spectrum remains a matter of debate. In particular, the lack of beneﬁt observed with renin angiotensin system blockers has raised questions regarding our understanding of the pathophysiology of HFpEF.It is also likely that heterogeneity in the clinical proﬁle of patients enrolled in these trials plays a role in the neutral results observed so far .This includes diﬀerent levels of natriuretic peptide activation as well as geographic variations which have been strikingly evidenced in the recently published TOPCAT trial with spironolactone New paradigms including a prominent role of comorbidities, inflammation, endothelial dysfunction and pro-hypertrophic signalling pathways have been proposed. Recent proof of concept trials using a phosphodiesterase inhibitor, an angiotensin receptor / neprilysin inhibitor, a soluble guanylate cyclase stimulator or a sino atrial If current blocker provide important insight for the development of novel therapeutic strategies in HFpEF. Key words: Heart failure. Pharmacology. Outcomes. Ejection fraction. 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society 特別講演９（SL9） The Role of Post-translational Modiﬁcations of SERCA2a in Heart Failure Roger J. HAJJAR Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai New York 10029, USA 特別講演 Recently, we discovered the impact of small ubiqutin-related modiﬁer type 1（SUMO-1）on the regulation and preservation of cardiac sarcoplasmic reticulum calcium ATPase（SERCA2a）pump function. The levels and activity of SERCA2a in cardiomyocytes are modulated in parallel with the levels of SUMO-1 protein. The amount of myocardial SUMO-1 is signiﬁcantly decreased in failing hearts and its knockdown results in severe heart failure （HF）in mice. Furthermore, we showed that SUMO-1 gene transfer led to restoration of SERCA2a levels, improved hemodynamic performance, and the reduced mortality in a murine model of pressure overload induced HF. More recently, we have demonstrated that SUMO-1 gene transfer and its combination with SERCA2a led to a reversal of HF in a porcine model of cardiac ischemia. We have recently identiﬁed and characterized a small molecule activator of cardiac SUMOylation, N106. In mice, N106 treatment signiﬁcantly improved pressure overload-induced hemodynamic dysfunction in a dose-dependent manner. However, mouse hearts with genetically inactivated SERCA2a protein showed no beneﬁcial eﬀects of N106 on cardiac hemodynamic function, suggesting the speciﬁcity of this compound. Taken together, our studies show that activation of SERCA2a SUMOylation is a new therapeutic target that can be stimulated by gene therapy or small molecules to improve cardiac function during HF. 128 プログラム・抄録集ジョイントシンポジウム 1（JS1）日本・韓国心不全学会（JHFS/KHFS）合同シンポジウム JS1-1 Current Status of Adult Heart Transplant in Korea: Twenty-year Experience Eun-Seok JEON、Ga Yeon LEE、Jin-Oh CHOI、Myung-Chan CHO、 Seok-Min KANG、Dong-Ju CHOI、Byung Su YOO Department of Cardiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, On behalf of Korean Society of Heart Failure JS1-2 Current System and Status of Heart Transplant Recipient Selection in Japan Taro SASAOKA1）、Yasushi SAKATA2）、Minoru ONO3）、Shinichi NUNODA4）、 Yoshiki SAWA5）、Mitsuaki ISOBE1） Department of Cardiovascular Medicine, Tokyo Medical and Dental University、 Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine、 Department of Cardiac Surgery, The University of Tokyo、 Division of Severe Heart Failure, Tokyo Women's Medical University Graduate School of Medicine、 Department of Cariovascular Surgery, Osaka University Graduate School of Medicine 1） 2） 3） 4） 5） <Background> The numbers of organ donation are quite limited due to the traditional value of life, death and religious outlook in Japan. To meet the social demand for equality and eligibility especially in recipient selection, Japanese Circulation Society established the council of assessment of heart transplant recipient eligibility in 1997. <Result> As of the end of June 2014, a total of 1510 applications（1090 recipient candidates）were processed in the council since January 1997. In the council, medical/social status and background were judged whether the candidates were eligible or not according to the web-based application form. 965（88.5%）candidates were judged as eligible for heart transplant recipient, 116（10.6%）candidates required re-assessment or pending, and 6 （0.6%）candidates were judged as non-eligible. Among those eligible candidates, 313（32.4%）were transplanted （204 transplanted in Japan, 109 transplanted abroad）, 288（29.8%）were dead while waiting for transplant, and 320 （33.2%）were on the waiting list. Survival rate of heart transplant in Japan is quite excellent（92.5% at 5 years, 89.8% at 10 years）; however, waiting duration for heart transplant exceeded over 900 days under mechanical circulation or intravenous inotrope support. <Conclusion> Excellent survival after heart transplant in Japan might be related to the strict assessment systems established for appropriate recipient selection. Promotion for donation is needed for achieving further heart transplant beneﬁt. 129 ジョイントシンポジウム Introduction and Method: Heart transplant is an invaluable option for the patients in the end-stage of heart failure. In Korea, over 900 cases of heart transplant were performed since the ﬁrst case in 1992. Here we summarized the trends and outcomes of heart transplants for twenty years in Korea. Among total 16 centers performing heart transplant, 11 centers participated the data collection. The comprehensive outcomes of heart transplants were retrospectively reviewed and analyzed. Results: Total 665 adult heart transplants were performed in 11 centers in Korea from November 11th, 1992 to December 31st, 2012. The number of heart transplant in Korea is 164 before 2000, and 501 after 2000. The percentage of the elderly recipients（ 60 years）is increased. In the primary cause of etiology, ischemic cardiomyopathy and hypertrophic cardiomyopathy was increased, but dilated cardiomyopathy was decreased. Recent long term survival rates was improved（estimated survival rates at 1 year, 3 year, 5 year, and 10 year; 83.4%, 77.1%, 71.6% and 57.0% before 2000, and 88.1%, 81.9%, 78.5%, and 70.0% after 2000, respectively）. Mortality due to acute graft failure was decreased（16.9% vs . 9.3%）,but mortality due to chronic graft failure and cardiovascular death was increased（3.9% vs. 4.6% and 11.7% vs . 19.4%）. Conclusions: Long-term survival rates of heart transplant in Korea was improved in spite of more elderly recipients and larger proportion of more-invasive mechanical supports. 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society JS1-3 Lessons From Acute Decompensated Heart Failure Patients in Korea （KorAHF）Registry Hyun-Jai CHO Seoul National University Hospital, Seoul, Korea Korean acute heart failure registry（KorAHF, NCT01389843）aims to evaluate clinical characteristics, management, hospital course, predictors of mortality, and short-term and long-term outcomes of patients hospitalized for acute heart failure syndrome（AHFS）. The study is expected to complete the enrollment of at least 5,500 patients in 2013 and to follow up until 2016. I will present the interim analysis（4,183 patients）. Ischemia was both the leading cause of HF and the most frequent aggravating factor in Korea. The mean length of hospital stay was 9 days and mean cost for an admission was about 8,000 US dollar. In-hospital mortality was 6.14 %. After discharge, 90-day mortality was 4.2% and rehospitalization was 15%. Multivariable logistic regression revealed that lung congestion, renal failure, Q wave, RBBB, SBP<100 and Na<135 were important predictors for in-hospital mortality. Characteristics and predictors of mortality diﬀer greatly in the subgroup. In contrast to HFrEF（ 40%）, patients with HFpEF（ 50%）were predominantly female and showed very different predictors of poor outcome. Body mass index （BMI）< 25 was the strongest predictor for mortality, suggesting that poor general condition and chronic co-morbidities would be important determinants in HFpEF. ジョイントシンポジウム These data demonstrate an unmet need for analysis of patient heterogeneity and socioeconomic burden of hospitalization. Therefore, ﬁndings of KorAHF may have important therapeutic implications to improve outcome of AHFS. JS1-4 Lesson from Acute Heart Failure（ATTEND）Registry in Japan Naoki SATO Cardiology and Intensive Care Unit, Nippon Medical School Musashi-Kosugi Hospital Hospitalized heart failure（HHF）is a major and growing public health concern and the leading cause of hospitalization in patients older than 65 years of age. The majority of costs are estimated to be attributable to the management of episodes of HHF. For prevention and improvement of HHF, the registry is so important that the acute decompensated heart failure（ATTEND）registry was conducted and 1 year-follow-up was ﬁnished. From the database from the ATTEND registry, we would like to show the results or considerations from viewpoints as follows: 1）risk stratification at admission, e.g., systolic blood pressure at admission, hyponatremia, renal function, and so on, 2）clinical signiﬁcance of non-pharmacological interventions in HHF, such as a pulmonary artery catheter, intra-aortic balloon pumping, and non-invasive ventilation, 3）major issues, which should be solved in managements of AHF in Japan, e.g., length of hospital stay, less use of non-invasive ventilation. Thus, we could learn lots of ﬁndings from the registry, which should be necessary to improve assessments and managements for AHF patients. Finally, I would like to discuss about the importance of registry and how to conduct it based on our experiences in the presentation. 130 プログラム・抄録集ジョイントシンポジウム 2（JS2）日本心不全学会（JHFS）̶日本心臓リハビリテーション学会（JACR）合同シンポジウム JS2-1 心不全治療としての運動療法：基礎から見た有効性の機序絹川真太郎、高田真吾、筒井裕之北海道大学大学院医学研究科循環病態内科学心不全患者は運動耐容能が低下しており、このことと予後悪化は密接に関連している。また、心不全患者における運動療法の予後改善効果も明らかにされている。心不全患者の運動耐容能低下には、心肺機能よりむしろ末梢の骨格筋異常が大きく関わっていることが知られている。骨格筋異常は、エネルギー代謝異常・酸化酵素減少・筋線維組成変移・筋萎縮などが報告されている。これらの異常を大別すると、骨格筋持久力に関しては筋線維組成変移も含んで骨格筋ミトコンドリアの質と量の異常が重要であり、筋量や筋萎縮に関してはタンパク合成と分解のバランスが重要である。近年、基礎的検討からこれらの骨格筋異常およびに運動トレーニング効果に関する分子機序が報告されている。我々は、脳由来神経栄養因子（Brain-derived neurotrophic factor）が骨格筋ミトコンドリア機能維持および運動トレーニング効果に重要な役割を果していることを明らかにした。本シンポジウムでは、運動療法の有効性の分子機序を概説する。ジョイントシンポジウム JS2-2 心不全治療としての運動療法のエビデンスの検証後藤葉一国立循環器病研究センター心臓血管内科 / 循環器病リハビリテーション部心不全に対する運動療法は、1980 年代後半から 90 年代前半に、運動耐容能低下を示す慢性心不全患者において心不全を悪化させることなく運動耐容能を改善させる手段として報告された。その後、運動療法が慢性心不全患者の自律神経機能や血管内皮機能を改善させることが見出され、2000 年代前半にメタ解析 ExTraMATCH において生存率や入院回避率改善効果が報告された。さらに 2007 年に大規模臨床試験 HF-ACTION において心血管イベント抑制効果や QOL 改善効果が報告され、現在ではガイドラインにおいて推奨される心不全治療法の 1 つとなった。一方、 HF-ACTION では運動療法群における長期予後改善効果が事前の予想より少なかったことから、運動療法へのアドヒアランスの重要性と長期維持の困難さが指摘されている。さらに、今後の課題として、心不全の運動療法の標準プログラムの確立、最適運動トレーニング様式の確立、および運動療法を含む包括的心不全管理プログラムとしての外来心臓リハビリテーションの普及、が挙げられる。ここでは、慢性心不全治療としての運動療法のエビデンスを検証し、今後の課題と展望を述べる。 131 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society JS2-3 Eﬃcacy and Problem of Out-patient Cardiac Rehabilitation as Disease Management Program for Heart Failure Patients Shigeru MAKITA Department of Cardiac Rehabilitation, Saitama International Medical Center, Saitama Medical University It is reported in Europe and America from the mid-1990s that disease management program（DMP）for heart failure including patient evaluation ,education and nurse home visit result in improvement of mortality, rates of readmission and QOL（N Engl J Med 1995, 333:1,190, Lancet 1999, 354:1,077）. But recently large scale of study appears in the report that eﬃcacy of the outcome cannot prove enough（N Engl J Med 2010, 363:2,301）. Consequently it is thought that the following managements are important such as patient-centered.care plan, tailor maid and interdisciplinary approach which made much of individuation of patients.It was not revealed the improvement of all death or rates of readmission about cardiac rehabilitation for heart failure patients mainly on exercise therapy in HF-ACTION（JAMA 2009, 301:1,439）. But in this paper, volume of exercise was associated with the risk of clinical events by sub-analysis. Therefore it was found the importance of patient support system for exercise adherence at the out-patient setting.Belardinelli demonstrated that mortality and QOL in the exercise therapy group for heart failure patients signiﬁcantly improved by RCT for ten years（JACC 2012, 60:1,521）, and in this study he applied coronary club which is well developed in Europe led by Germany. It may be said that importance of support system of long-term, safe exercise therapy in the community was recognized. ジョイントシンポジウム JS2-4 わが国で心不全診療に心臓リハビリテーションを組み込むために何が必要か？猪又孝元北里大学医学部循環器内科学心臓再同期療法（CRT）の普及が芳しくない。不整脈専門医やインターベンション医が技術的に CRT に飛びついても、重症心不全は半永久的に心不全管理を続けねばならない。1 点介入で決着がつかぬ対象に、距離を置きはじめたのかもしれない。要は、全体像を見据えたうえで、役割を意識して一介入を組み立てられるかである。心不全に対する心臓リハビリテーション（心不全リハ）も同様であろう。わが国における心不全リハの最大の特徴は、施設間、医師間の温度差が大きい点である。これは、心不全診療に対する実地医師の温度差から生ずる部分が大きい。心リハスタッフ側には多面的包括診療を担うチーム医療の一員としてのコミュニケーション体制の確立が、管理統括医師側からは心リハの役割を十分認識した上でのマネージメント能力が求められる。そして、これをシステムとして標準化させることが重要である。急性心筋塞後症例では、ややもすると独立した形で粛々と心リハが進行し、担当主治医が全く関与・認識できていなかった。今、心不全リハに求められるのは、各職種がひとりの患者に対してアウトカムを共有し、包括的な体制を築きあげるフォーマット作りであろう。 132 プログラム・抄録集ジョイントシンポジウム 3（JS3）日本・欧州・米国心不全学会（JHFS/ESC-HFA/HFSA）合同シンポジウム JS3-1 Novel Natriuretic Peptides for Acute Heart Failure Stefan D. ANKER University Medical Center, Göttingen, Germany The morbidity and mortality in acute heart failure is still very high. For a long time, natriuretic peptides are considered a possible therapeutic option. The presentation will review past and ongoing trials. One of the drugs currently in phase III testing is ularitide, which is the chemically synthesised form of the human natriuretic peptide urodilatin. Urodilatin is produced in humans in distal renal tubule cells. Physiologically, urodilatin appears to be the natriuretic peptide most involved in sodium homeostasis. Ularitide also exerts vasodilation, diuresis and natriuresis through the natriuretic peptide receptor / particulate guanylate cyclase / cyclic guanosine monophosphate pathway. TRUE-AHF is the pivotal Phase III study in acute decompensated heart failure to study the impact of ularitide on outcomes. Synthetic natriuretic peptides （like CD-NP） are also in development and will be reviewed as well. ジョイントシンポジウム JS3-2 Modulation of Cardiac Metabolism in Heart Failure Giuseppe M.C. ROSANO IRCCS San Raﬀaele, Roma ‒ ITALY In heart failure substantial changes occur in cardiac energy metabolism, as a consequence of the altered autonomic nervous control of the cardiovascular system and the over-activation of the renin-angiotensinaldosterone system. Some of these metabolic changes are beneficial and may help the heart adapt to the altered haemodynamic conditions. However, most of the changes are maladaptive and contribute to the severity of the left ventricular dysfunction/stiffness, myocardium, cell death and ultimately to contractile dysfunction. In heart failure the relative substrate concentration is the prime factor deﬁning preference and utilization rate. Allosteric enzyme regulation and protein phosphorylation cascades, partially controlled by hormones such as insulin, modulate the concentration eﬀect; together they provide short-term adjustments of cardiac energy metabolism. The expression of metabolic genes is also dynamically regulated in response to developmental and （patho）physiological conditions, leading to long-term adjustments. Given the cardiac metabolic alterations at rest and during exercise occurring in patients with heart failure, therapeutic approaches aimed at reducing myocardial expenditure and at improving cardiac metabolism through reduction of heart rate and optimisation of the utilization of metabolic substrates should result in an improvement of left ventricular function. The inhibition of FFA oxidation improves cardiac metabolism at rest and reduces the decline of left ventricular function due to chronic hypoperfusion and repetitive episodes of myocardial ischemia improving morbidity and mortality in patients with heart failure. 133 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society JS3-3 Troponin I-3 Kinase: a Key Regulator of Ischemic Injury: Ready for the Clinic? Thomas FORCE Vanderbilt University School of Medicine, Division of Cardio-vascular Medicine, USA The troponinI3 kinase is truly a remarkable kinase that regulates everything from ischemic injury, to obesity, and may impact on viral myocarditis. I will explore each of these entities and will discuss where we should go from here with this multipotent kinase. ジョイントシンポジウム JS3-4 Treating Heart Failure with New Drugs That Target Both the Heart and the Adrenal Gland Burns C. BLAXALL Cincinatti Children's Hospital, USA Background: elevated sympathetic nervous system activity is a salient characteristic of heart failure （HF）progression. It causes pathologic desensitization of β-adrenergic receptors（β-AR）, facilitated predominantly through Gβγ-mediated signaling. The adrenal glands are key contributors to the chronically elevated plasma catecholamine levels observed in HF, where adrenal α2-AR feedback inhibitory function is impaired also through Gβγ-mediated signaling. Objective: we propose simultaneous inhibition of Gβ γ signaling in the heart and the adrenal gland as a novel therapeutic approach for HF. Methods and results: we investigated the efficacy of a small molecule Gβγ inhibitor, gallein, in a clinically relevant, pressure-overload model of HF. Daily gallein treatment（10 mg/kg/day）, initiated four weeks following transverse aortic constriction, improved survival and cardiac function, and attenuated cardiac remodeling. Mechanistically, gallein restored β-AR membrane density in cardiomyocytes, attenuated Gβγ-mediated GRK2-PI3Kγ membrane recruitment, and reduced Akt and GSK-3β phosphorylation. Gallein also reduced circulating plasma catecholamine levels as well as catecholamine production in isolated mouse adrenal glands by restoring adrenal α2-AR feedback inhibition. In human adrenal endocrine tumors（pheochromocytoma）, gallein attenuated catecholamine secretion, as well as GRK2 expression and membrane translocation. Conclusions: these data suggest small molecule Gβγ inhibition as a systemic pharmacologic therapy for HF by simultaneously normalizing pathologic adrenergic/Gβγ signaling in both the heart and the adrenal gland. Our data also suggest important endocrine/cardiovascular interactions and a possible role for small molecule Gβγ inhibition in treating endocrine tumors such as pheochromocytoma, in addition to HF. 134 プログラム・抄録集 JS3-5 Managements for Congestion in Acute Heart Failure in Japan - The Earlier Intervention, the Better Outcome? Naoki SATO Cardiology and Intensive Care Unit, Nippon Medical School Musashi-Kosugi Hospital In acute heart failure（AHF）patients, the major therapeutic target is congestion. To improve outcome of AHF, evaluation and managements of congestion are the important issues. From the ATTEND registry, which is the cohort study of AHF in Japan, in-hospital mortality in patients with both jugular venous distention and leg edema was almost double compared to that of patients with only one of each. Therefore, congestion should be evaluated using appropriate scoring, such as assessing and grading congestion suggested by the European Society of Cardiology and the European Society of Intensive Care Medicine（Eur J Heart Failure 2010;12:423433） . In terms of organ protection in AHF, "the earlier intervention, the better outcome" might be important. This concept in AHF patients with cardiac pulmonary edema has already supported by several studies. How about ﬂuid retention? In AHF patients with ﬂuid retention, it is not clariﬁed whether or not it is beneﬁcial to restore ﬂuid status by earlier pharmacological intervention for improvement of outcome. In Japan, tolvaptan, an aquaretic diuretic, can be used for ﬂuid retention in AHF. Several studies have demonstrated tolvaptan can protect renal function by its earlier initiation compared to conventional therapies. Although further studies should be needed, "the earlier intervention, the better outcome" might be true in AHF patients with ﬂuid retention as well as pulmonary edema. ジョイントシンポジウム JS3-6 How to Treat Acute Decompensated Heart Failure? Aquaresis or Diuresis? Koichiro KINUGAWA The Department of Therapeutic Strategy for Heart Failure, The University of Tokyo, Tokyo, Japan Loop diuretics are commonly used in heart failure patients, but they are sometimes associated with insuﬃcient response as well as adverse events. In such diuretics-resistant cases, tolvaptan, a vasopressin type 2 receptor antagonist, shows the improvement of volume overload without electrolyte imbalance. Tolvaptan was launched in Japan in 2010 under the unique indication, and a post-marketing surveillance has been performed to evaluate the safety and eﬃcacy of tolvaptan under the real-world clinical setting. I will discuss about the data from PMS in this session. Unfortunately, a large scale randomized study, the EVEREST trial did not prove a long term beneﬁt of tolvaptan in ADHF patients. However, Japanese experience has revealed the existence of certain number of nonresponders to this drug. If only responders are treated, there may be a considerable improvement of long term prognosis. I will also discuss about responder/nonresponder issues of tolvaptan and its relevance to long term beneﬁt. 135 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society シンポジウム１（S01）虚血性心不全 S01-1 Impact of Heart Failure on In-Hospital Mortality in Patients with Acute Myocardial Infarction in the Troponin Era Masaharu ISHIHARA Division of Coronary Heart Disease, Hyogo College of Medicine, Hyogo, Japan Since the introduction of reperfusion therapy, prognosis of acute myocardial infarction（AMI）has dramatically improved. It has been demonstrated that the presence of heart failure on admission is a strong predictor of death during the index episode of AMI. Recently, new definition of AMI using cardiac troponin as the preferred biomarker has been proposed. In the current study, we investigated how admission heart failure aﬀects in-hospital mortality after AMI in the troponin era. Methods: Japanese registry of acute Myocardial INfarction diagnosed by Universal dEfiniTion（J-MINUET）is a prospective and multicenter observational study conducted in 31 institutions （UMIN000010037）. Since July 2012, consecutive patients diagnosed as having spontaneous AMI（ type 1 or 2）by universal deﬁnition who admitted to participating institutions within 48 hours of symptom are entered into this registry. In the interim analysis at January 2014, 2937 patients were registered. Results: 67% of the patients were STEMI. Inhospital mortality was higher as Killip class advanced in both patients with STEMI and those with NSTEMI. Final TIM-3 was associated with lower mortality in each Killip class. Conclusion: Heart failure is still a strong predictor of death after AMI even in the contemporary troponin era. Importance of successful reperfusion was re-emphasized. S01-2 Open Artery Hypothesis Returns: CTO Treatment in Patients with Ischemic Heart Failure シンポジウム Shin TAKIUCHI Department of Cardiology, Higashi Takarazuka Satoh Hospital Chronic hypoperfusion due to the presence of a chronic total occlusion（CTO）on a viable myocardium can cause ventricular dysfunction, and may lead to symptoms such as exercise intolerance and heart failure resulting from this dysfunction. It therefore seems logical that the opening of an occluded artery which irrigates a viable but dysfunctional myocardium could reverse this dysfunction and improve these patients symptoms and prognosis. Some registries have reported that patients with complete revascularization have a better prognosis than those with incomplete revascularization, including the presence of an untreated CTO. However, there are many negative views about this open artery hypothesis , because most available data suggest a very modest improvement in ventricular function as a result of opening an occluded artery. The improvement in the prognosis of patients with ventricular dysfunction due to revascularization of CTO is currently a topic of heated debate. Because the success rate of percutaneous treatment of CTO improved splendidly by development of new technique and devices, it has become unnecessary to hesitate PCI to severe CTO lesions. This symposium will review the available evidences supporting percutaneous coronary intervention（PCI）for CTO, introducing several recent advanced PCI techniques for CTO and the cases in which the PCI for CTO were eﬀective in the improvement of the ischemic heart failure. 136 S01-3 Treatment Strategy of Ischemic Heart Failure, an Overview Yukihito SATO Division of Cardiovascular Medicine, Hyogo Prefectural Amagasaki Hospital, Amagasaki, Japan Etiological data showed that coronary artery disease （CAD） is the main leading cause of heart failure（HF）and that the presence of CAD has been shown to be independently associated with a poor prognosis. The therapeutic strategy is aiming prevention from reinfarction, sudden death and left ventricular （LV） remodeling. Recently, large scale clinical trials have documented the pharmacological therapies in patients with post myocardial infarction. ACE inhibitors, beta blockers and aldosterone antagonists has been shown to （MI） and reduce cardiac death, non-fatal myocardial infarction prevent LV remodeling. Besides the pharmacological therapies, device therapy, such as cardiac resynchronization therapy or implantable cardioverter deﬁbrillators （ICD）, are eﬀective in certain patients with CAD and HF. However, the impact of inappropriate ICD shock on the HF needs to be determined. Finally, most patients with HF and CAD are in a gray zone without clear evidence of the need for surgical therapy, including revascularization, surgical treatment of mitral regurgitation, and ventricular restoration, even after the STICH trial that compared the strategy 1）medical therapy alone vs. medical therapy +CABG and 2）CABG alone vs. CABG +ventricular reconstruction in patients with severe reduced LVEF patients with CAD. This symposium will review the current understanding of the therapeutic strategies in patients with CAD and HF. S01-4 Evaluating The Morphological and Hemodynamic Status in Patients with Ischemic Heart Failure Using Several Imaging Modalities Noriaki IWAHASHI、Toshiaki EBINA、Kazuo KIMURA Divusion of Cardiology, Yokohama City Univesity Medical Center, Yokohama, Japan The prediction of left ventricular（LV）remodeling is important and preventing its progression to ischemic heart failure（IHF）is crucial. Two major causes of IHF are well recognized: HF with reduced ejection fraction（EF）（HFrEF）and HF with preserved EF（HFpEF）. IHF typically occurs in patients who have not undergone adequate reperfusion therapy, who have large infarct size, or who have histories of myocardial infarction. Infarct size and LV function can be estimated using cardiac MRI（CMR）. However, the use of CMR is contraindicated in patients with renal failure or some mechanical devices（e.g., implantable cardioverter-deﬁbrillators and pacemakers）. Radioisotopes（Tc or Tl）can be used instead of CMR for patients with these limitations. The resolution of isotope methods is not as high as with CMR; however, the resolution is satisfactory for a large portion of patients so these methods are still useful. Echocardiography （Echo）enables doctors to assess both the systolic and the diastolic function. Strain imaging provides assessments of systolic function with greater accuracy than EF because strain imaging has no tethering eﬀect. Echo provides estimates of diastolic function using various Doppler imaging devices. Hemodynamic status and diastolic function can also be estimated using tissue Doppler imaging（E/ e'）. Patients with HFpEF can be treated using Echo. Patients with ischemic HF should be treated using these modalities accompanied by appropriate revascularization and medications. プログラム・抄録集シンポジウム２（S02）心不全の最新の画像診断（MRI、CT、エコーなど） S02-1 S02-3 Eﬀectiveness of Novel Non-Invasive Measurement After-Load Indexas Predictor in Patients with Acute Decompensated Heart Failure 1） 2） 2） Masataka WATANABE 、Takahiro OHARA 、Takuya HASEGAWA 、 Hideaki KANZAKI2）、Kazuhiko HASHIMURA3）、 Masafumi KITAKAZE2）、Akira YAMASHINA1） Department of Cardiology, Tokyo Medical University、 2）National Cerebrarl and Cardiovascular Center, Osaka, Japan、3）Hanwa Memorial Hospital, Cardiovascular center 1） Aim: Because the methods of measurement after-load is not as straightforward available with noninvasive equipment nowadays, the clinical applicability of after-load remains poorly deﬁned in patients with systolic dysfunction. Methods and results: The primary efficiency end point was increasing cardiac output. Eleven patients categorized to be in the subset of Cold & Wet were enrolled; pulmonary artery catheter was introduced into all patients to investigate PCWP and systemic vascular resistance （SVR）. The combination of（the velocity of mitral regurgitation（MRV））/ （the velocity-time integral of left ventricular outﬂow tract（VTILVOT））and heart rate（HR）was formulated as an approximation of Ea. Compared to correlation between increasing cardiac output and the catheter- or echodoppler cardiogram-derived hemodynamic parameters. PCWP was not correlated well with % change CO, as well as, pre-treatment PCWP was not predicted increasing CO after the treatment.（r2=0.0489, P=0.3488; delta PCWP（%）versus % change CO, and r2=0.121, P=0.13, Y = -19.58 -0.3; prePCWP versus % change CO）. Catheter-derived SVR and AFI negatively correlated well with precent change CO.（r2=0.61, P> .0001, Y = 4.177; 1.58 delta PCWP（%）versus precent change CO, and r2=0.51, P=0.0004, Y = 5.08; 1.249 pre-PCWP versus precent change CO）Conclusion: The AFI provides a reliable noninvasive predictor of increasing CO in patients with heart failure. Assessment of Myocardial Fibrosis and Prognosis of Non-Ischemic Cardiomyopathies by Using Non-Contrast T1 Mapping Emi TATEISHI1）、Yoshiaki MORITA2） Department of Cardiology, Saiseikai Suita Hospital, Osaka, Japan、 Department of Radiology, National Cerebral and Cardiovascular Center, Osaka, Japan 1） 2） Myocardial ﬁbrosis is associated with worsening ventricular systolic function, progressive remodeling, and increased ventricular stiffness in patients with heart failure. Late gadolinium enhancement（ LGE）on cardiac magnetic resonance （CMR） has been established as an useful and less invasive method for evaluating myocardial fibrosis, and it plays an important role in the diagnosis of cardiomyopathies and the assessment of prognosis. Moreover, the novel CMR technique, T1 mapping, enables direct quantification of the extracellular volume（ECV）by the measurement of T1 relaxation time before and after gadolinium administration. Since ECV shows good correlation with histological collagen volume fraction, T1 mapping is a promising technique for accurate evaluation of not only focal ﬁbrosis, which can be assessed by LGE, but also diﬀuse myocardial disorder which cannot be detected by LGE. Recently, several studies have proposed that T1 mapping before gadolinium administration, non-contrast T1 mapping, is potentially valuable for the quantitative assessment of focal and diffuse diseased myocardium. T1 mapping may therefore serve as an eﬀective screening test for the patients with low pre-test likelihood for the presence of cardiomyopathy and those in whom contrast administration is contraindicated. S02-2 New Horizon of the Cardiac Function Assessment: From Tissue Tracking to Flow Tracking National Cerebral and Cardiovascular Center Despite the advances in echocardiographic technique, there still is discrepancy between patient condition and imaging result. This may be due to the fact that conventional measurements have limitation on detecting subtle myocardial tissue damage or impaired regional motion. New cardiovascular imaging technology has enabled us to track tissue characterization and visualize complex movement of myocardial contraction. Strain and strain rate derived by twodimensional speckle tracking are tools to detect regional and global early functional abnormalities without angle dependency. It has been applied to the assessment of resting ventricular function, the assessment of myocardial viability and stress testing for ischemia. The technique for tracking myocardium has recently been applied to track blood ﬂow pattern frame by frame. Flow of the blood may be immediately aﬀected by changes in left ventricular morphology and intracavity filling pressures. Therefore, flow may be a more robust marker for characterizing chamber ﬁlling dynamics. There is an alternative technique to visualize ﬂow patterns by using color Doppler and tissue tracking method. Clinical application of these techniques is still waiting but the pattern of diastolic volumetric filling may provide an index that links diastolic filling to systolic stroke volume. The aim of this session is to summarize the new technologies of echocardiography and to investigate the clinical application of the individual techniques. Heart Failure and ECG-Gated Single-Photon Emission Computed Tomography Naoya MATSUMOTO1）、Yasuyuki SUZUKI1）、 Atsushi HIRAYAMA2） Nihon University surugadai Hospital, Department of Cardiology, Tokyo, Japan、2）Nihon University School of Medicine, Department of Medicine, Division of Cardiology 1） First of all, myocardial perfusion single-photon emission computed tomography（SPECT）will be used for the differentiation of ischemic cardiomyopathy and nonischemic cardiomyopathy（DCM）. Basically, non-ischemic cardiomyopathy shows essentially normal perfusion and global hypokinesis of the left ventricle with an impaired ejection fraction. ECG-gated SPECT calculates regional wall motion（mm）, wall thickening（%）and time to maximum thickening（TTMT: msec）with QGS software. The patients with DCM showed higher maximum difference of TTMT （deltaTTMT）and coefficient of variation of TTMT （CVTTMT）than those in normal control subjects（16.4 vs 7.8, . These indices could p<0.0001 and 206 vs 103msec, p<0.0001） be a useful marker for the evaluation of the severity in patients with left ventricular dyssynchrony. TTMT is also a useful tool to evaluate the eﬀect of cardiac resynchronization therapy （CRT） . Dyssynchrony index （DI） which was derived from deltaTTMT may contribute to the evaluation and prediction of CRT. ECG-gated SPECT has a superiority to have those indices without time and eﬀort. 137 シンポジウム Makoto AMAKI、Akira FUNADA、Hiryuki TAKAHAMA、Takahiro OOHARA、 Takuya HASEGAWA、Yasuo SUGANO、Masanori ASAKURA、 Hideaki KANZAKI、Masafumi KITAKAZE、Toshihisa ANZAI S02-4 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S02-5 How Can We Use the Cardiac CT in Diagnosis and Management of Heart Failure? Yasushi KOYAMA Cardiovascular Center, Sakurabashi-Watanabe-Hospital As concern about cardiac CT, the radiation exposure and contrast media were limitations for a long time. In recent years, the reduction of radiation dose and contrast media were achieved by both the administration of ultra-short-acting β-blockers and the usage of radiation dose reduction technology such as iterative reconstruction. As the results, the basic cardiac function analysis in one cardiac cycle or several scans in one CT examinations has become possible in clinical setting with low radiation dose and less contrast media. For patients with morphological limitations of CT angiography （CTA）such as intermediate coronary artery stenosis and/or severe coronary artery calcification, the pharmacological stress CT perfusion （CTP）and FFR-CT are now available for the detection of ischemia. Moreover, the myocardial imaging such as "Delayed enhancement" on MRI, has been becoming possible for the assessment of myocardial viability with coronary artery trees on CT. In near future, the progress of dual source technology might also contribute to the myocardial viability imaging. In addition, the advanced cardiac electrophysiological functional evaluation with high temporal resolution is also now updating, for example, the preoperative and postoperative CRT, visual and quantitative assessment of dyssynchrony in patients with heart failure. The latest 4D-Imaging without dead angle might have great potential on physiological functional evaluation. In this meeting, I will present the comprehensive diagnosis of cardiac CT for heart failure patients using two approaches such as morphological and physiological assessment, while presenting cases. シンポジウム 138 プログラム・抄録集シンポジウム３（S03）HFpEF - 臨床 S03-1 Update on Heart Failure with Preserved Ejection Fraction Carolyn S.P. LAM National University Health System Singapore Heart failure with preserved ejection fraction （HFPEF）represents one of the greatest unmet needs in Cardiology currently. Barely 25 years ago, we did not believe that heart failure could exist in the presence of an apparently normal ejection fraction. We now know that HFPEF not only exists and can be diagnosed, but that it currently constitutes half the heart failure population in many parts of the world and will become the predominant type of heart failure in future. Furthermore, it is a highly morbid and deadly disease. Most signiﬁcantly, our attempts to extrapolate proven therapies in heart failure with reduced ejection fraction（HFREF）to this population have uniformly failed to improve outcomes in HFPEF, and in fact, this is a syndrome still in search of a cure. The controversies surrounding HFPEF is reflected in the transition of nomenclature used to refer to it, from diastolic heart failure to heart failure with normal systolic function, heart failure with normal ejection fraction, and now heart failure with preserved EF. This evolution also reﬂects our increasing understanding of this important syndrome. This lecture therefore aims to summarize the current state of understanding in HFPEF. S03-3 Lack of Inertia Force of Late Systolic Aortic Flow is a Cause of Heart Failure with Preserved Ejection Fraction Nobuyuki OHTE Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences Inertia force（IF）of late systolic aortic flow is observed in left ventricles with good systolic function. A lack of IF may be related to left ventricular（LV）diastolic dysfunction and the pathogenesis of heart failure（HF）with preserved LV ejection fraction（EF）. Accordingly, we examined the relationships between the IF and LV systolic and diastolic functions. IF was calculated from the LV pressure（P）-dP/ dt relation. The IF significantly correlated with the LV systolic function parameters such as LVEF and LV endsystolic volume index in patients with preserved LVEF. It also significantly correlated with the parameters of LV early diastolic function, such as the time constant τ of LV relaxation and the propagation velocity of LV early diastolic filling flow. Furthermore, in a retrospective outcomeobservational study in which combined subsequent HF and all-cause mortality were set as a study endpoint, fewer patients with IF reached the endpoint in comparison with patients without IF during follow-up. In conclusion, good LV systolic function speeds LV relaxation and enhances LV early diastolic ﬁlling through the IF. A lack of IF causes LV isolated diastolic dysfunction and brings a poorer outcome. One of the causes of HF patients with preserved LVEF is relative or mild systolic dysfunction, although LVEF is more than 50% in this category of patients. S03-2 S03-4 Respiratory Muscle Weakness in Patients with Heart Failure with Preserved Ejection Fraction Akihisa HANATANI、Sinichi IWATA、Yoshiki MATSUMURA、 Kenichi SUGIOKA、Shoichi EHARA、Kenei SHIMADA、 Minoru YOSHIYAMA Yoshiharu KINUGASA1）、Kensaku YAMADA1）、Takeshi SOTA2）、 Mari MIYAKI3）、Shinobu SUGIHARA1）、Masahiko KATO1）、 Kazuhiro YAMAMOTO1） Department of Cardiovascular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine Tottori University、2）Division of Rehabilitation Tottori University Hospital、3）Division of Clinical Laboratory Tottori University Hospital Approximately 30-50% of patients with heart failure have preserved left ventricular ejection fraction（heart failure with preserved ejection fraction: HFpEF）. But a prognosis of patients with HFpEF was reported to be poor similar to that of patients with heart failure with reduced ejection fraction（HFrEF）. The serum concentration of cardiac troponin T（TnT）is a speciﬁc and highly sensitive marker of myocardial injury and the diagnostic and prognostic value of TnT has been established in patients with HFrEF. But the prognostic value of TnT in patients with EFpEF is not clear. We examined the relationship between the high-sensitivity troponin T（hs-TnT）level and cardiac events in patients with EFpEF. From October 2011 to December 2013, 54 patients with EFpEF were administered in our hospital. We divided these patients into two groups, normal hs-TnT group （n=21）and high hs-TnT group（n=33）,and compared cardiac events（cardiac death and re-hospitalization due to worsening heart failure）in follow up periods. In high hs-TnT group, the event-free rate was almost significantly lower than that of normal hs-TnT group（P=0.06）. Our data suggest that measurements of hs-TnT may be useful to predict the prognosis in patients with HFpEF similar to HFrEF. 1） Background Previous studies have shown that respiratory muscle weakness（RMW）is associated with exercise intolerance in patients with heart failure with reduced ejection fraction. However, in patients with heart failure with preserved ejection fraction（HFpEF）,such relationship remains unclear. Methods The present study enrolled a total of 36 patients with HFpEF（mean age 77±22, 52.8% male, EF > 45%）who were hospitalized with HF in our institution. Respiratory muscle strength was assessed by a percent maximum inspiratory pressure to normal predicted value（%MIP）, and exercise tolerance was assessed by 6-minute walk distance（6MWD）before hospital discharge. Results RMW deﬁned as %MIP<70% was prevalent in 36.1% of patients. Patients with RMW had signiﬁcantly lower percent vital capacity to normal predicted values（%VC）and lower albumin level compared with those without RMW（all p<0.05）. They had also signiﬁcantly lower quadriceps muscle strength and 6MWD than those without RMW（all p<0.05）. Multivariate regression analysis showed that lower %MIP was independently associated with reduced 6MWD as well as higher age and lower quadriceps muscle strength（p<0.05）. Conclusions RMW is a frequent co-morbidity, and is independently associated with exercise intolerance in patients with HFpEF. Further investigations are necessary to clarify the beneﬁcial eﬀect of inspiratory muscle training in these patients. 139 シンポジウム Prognostic Value of High-Sensitivity Troponin T in Patients with Heart Failure with Preserved Ejection Fraction 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S03-5 Furosemide or Azosemide: Which is Better for Management of HFpEF? Shinichi HIROTANI Devision of Cardiovascular Medicine, Hyogo College of Medicine, Nishinomiya, Japan It remains undefined which loop diuretics is better for management of HFpEF. To address this issue, we performed a subanalysis of the J-MELODIC Study. The J-MELODIC Study was a prospective, multicenter, randomized study speciﬁcally aimed at comparison of the therapeutic eﬀects of furosemide, a short-acting loop diuretic, and azosemide, a long-acting one, in patients with heart failure（HF）and the result was long-acting diuretics are superior therapy. The endpoint of this subanalysis was a composite of cardiovascular death and unplanned admission to hospital for congestive HF in patients with EF >/= 45%. Of 320 patients enrolled in the J-MELODIC study, 209 patients were EF >/= 45%. The composite outcome was comparable between diuretics. However, subtracting patients with β -blocker, azosemide was better. シンポジウム 140 プログラム・抄録集シンポジウム４（S04）急性心不全における評価指標を考える S04-1 S04-3 Heterogenous Nature of Acute Heart Failure Syndrome and The Necessity of a Standardized Grading System for Its Clinical Presentation Characteristics, Management, and Outcomes for Patients During Hospitalization Due to Worsening Heart Failure in Japan Versus Europe and US Kazuhiko HASHIMURA Hiroyuki TSUTSUI CardioVascular Center, Hanwa Memorial Hospital, Osaka, Japan Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan ACE inhibitors/ARBs, beta blockers, mineral corticoid receptor antagonists and digoxin have shown effectiveness in HFrEF, but not in HFpEF. Both of HFrEF and HFpEF are considered a "syndrome", due to its heterogenous nature;（1）pathophysiology （arterial underﬁlling, volume accumulation, central volume shift and abnormal blood pressure control by carotid baroreceptor etc.）（2） , comorbid disease（hypertension, CKD, DM, lipid disorder, etc.）（3） , left ventricular geometry（normal, dilated, concentric hypertrophy, concentric remodeling, eccentric hypertrophy）and （4）clinical presentation（rapid or gradual onset, pulmonary or systemic congestion, body weight gain + or -, etc.）. This heterogeneity may have resulted in lack of signiﬁcant results in previous heart failure syndrome-related large-scale clinical trials. A more narrowed inclusion criterion is therefore essential in future studies.In addition to the heterogeneity of heart failure syndrome, the absence of a standardized criterion to evaluate the degree of pulmonary/ systemic congestion, and peripheral perfusion may have also complicated result interpretation in these trials. Due to this absence, a thorough clinical assessment analyzing the degree of congestion is not routinely performed during hospitalization and before discharge. Future practice should involve; 1）a subjective and objective grading system assessing volume status with dynamic postural change and 2）utilization of diagnostic devices capable of detecting asymptomatic congestion. S04-2 Heart failure（ HF）is a complex condition with substantial morbidity and mortality and healthcare needs and economic burden for repeated worsening. Current clinical profiles of patients hospitalized with worsening HF have been documented based on large-scale hospital registries such as The EuroHeart Failure survey（EHFS）in Europe and ADHERE and OPTIMIZEHF in the USA. However, the management strategies of worsening HF may be different from countries according to healthcare system. Thus, more complete understanding of characteristics, in-hospital management, and outcomes of these patients in an observational database is deﬁnitely needed in Japan. The Japanese Cardiac Registry of Heart Failure in Cardiology （JCARE-CARD）studied prospectively the characteristics and management in a broad sample of patients hospitalized with worsening HF in Japan and the outcomes including death and rehospitalization were followed in a web-based registry. The characteristics, clinical status, and laboratory data on admission were similar between JCARE-CARD and registries from the USA and Europe. Management was also similar except for higher use of carperitide and angiotensin receptor blocker. The most striking diﬀerence was the longer length of stay in Japan. These ﬁndings would be useful for the development of optimal management strategy for Japanese patients hospitalized with worsening HF. S04-4 Experience of Coordinating a Clinical Trial on Acute Heart Failure in Japan Shin-Ichi MOMOMURA Masanori ASAKURA Division of Cardiovascular Medicine, Saitama Medical Center Jichi Medical University, Saitama, Japan Department of Clinical Medicine and Development Acute decompensated heart failure is a life threatening condition and stabilization of hemodynamics has been thought to be the primary therapeutic target. To quantitatively evaluate hemodynamics, data obtained by pulmonary arterial catheterization such as cardiac output, pulmonary wedge pressure and etc. have been standard indicators for the evaluation of treatment eﬀect in ADHF. Indeed, these parameters were dramatically improved by intravenous administration of positive inotropic drugs including catecholamines and phosphodiesterase III inhibitors. However these drugs turned out not necessarily to improve survival of patients with ADHF. Clinical signs and symptoms including severity of dyspnea, rales, and the third heart sound are important predictors of prognosis of ADHF. Quantitative assessment of these parameters should be revisited as a marker of clinical studies.Since ADHF is associated high pre- and post- discharge mortality and morbidity, therapeutic measures to ADHF should be chosen in view of not only short-term hemodynamic improvement but also clinical outcomes including survival and readmission. Many recent clinical trials on ADHF actually adopt clinical outcomes for endpoints. Eﬃcient surrogate markers for clinical outcomes should also be sought. Biomarkers including BNP, ST2, galectin, NGAL, copeptin and etc. could be a good surrogate markers. Renal function could also be an indispensable endpoint, since worsening of renal function is known to be a strong predictor of mortality and morbidity in ADHF. Treatment strategy of chronic heart failure has changed dramatically over the last 20 years. Treatments for acute heart failure are also making steady progress. However, further development of therapies for acute heart failure is required. Poor post-discharge prognosis of patients hospitalized for acute heart failure is a big issue. We need to develop the new drugs in order to improve postdischarge mortality rate of patients with acute heart failure. Most clinical trials for approval of new cardiovascular drugs in Japan conducted by pharmaceutical companies. Investigator-initiated clinical trials for new drug approval have recently been conducted. We have conducted a multicenter randomized double-blinded clinical trial named Earlier trial to evaluate the efficacy of eplerenone on acute heart failure. We have faced many diﬃculties on coordinating a clinical trial such as a study design including a definition of study subjects or primary endpoints, a selection of participant hospitals, funding for conducting a trial, shortage in human resources for clinical trial, how to interact with stake holders. We would like to discuss these issues in this symposium. 141 シンポジウム Transition of Clinical Indicators in Acute Decompensated Heart Failure 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S04-5 The Clinical Evaluation of Drugs in the Treatment of Acute Heart Failure : The Regulatory Perspective Kaori SHINAGAWA Pharmaceuticals and Medical Devices Agency Acute heart failure（ AHF）is a growing public health problem, and very few treatments have been introduced in the last 10 years. Since it is diﬃcult to conduct large-scale conﬁrmatory trials for mortality in Japan, it is necessary to provide endpoints for HF trials in Japan. For this purpose, the guidelines on the clinical evaluation of drugs in the treatment of heart failure were issued in 2011. Requirements for a drug to receive approval of an indication for AHF are 1. improvements in short-term mortality and morbidity, and 2. at least maintain long-term mortality. Just improvement of hemodynamics is not sufficient, we also need a shortterm mortality beneﬁts or an improvement of clinical signs and symptoms related to hemodynamics.The evaluation of efficacy will depend on the pharmacological profile and mechanism of action of the drug and the expected therapeutic targets. On top of choosing the optimal primary endpoint, secondary endpoints should include endpoints related to symptoms and QOL. Issues for drug development for AHF include the wide variety of disease backgrounds, and the difficulty to reach consensus on how to measure and evaluate subjective endpoints.Moving forward, standardization and validation of end-points measures is critical. Future collaborative efforts between academia, industry, and regulatory agencies will be required in order to evaluate new therapies in the most eﬃcient way possible. シンポジウム 142 プログラム・抄録集シンポジウム５（S05）重症難治性心不全(NYHA3-2)へのSHDインターベンション治療 S05-1 Ballon Aortic Valvuloplasty as an Eﬀective Bridge to Transcatheter Aortic Valve Implantation for the Patients with Severe Aortic Stenosis Kentaro HAYASHIDA Keio University School of Medicine Transcatheter aortic valve implantation（TAVI）is widely accepted as an effective treatment for the patients with severe aortic stenosis who are inoperable or at high-risk for conventional surgical aortic valve replacement. Balloon aortic valvuloplasty（BAV）is now re-emerging as a promising therapeutic bridge to TAVI, especially in the patients with extremely high-risk condition, such as cardiogenic shock, very low left ventricular function and infection etc... In this presentation, we aim to clarify current indications of BAV in this contemporary TAVI era. S05-2 TAVI with Balloon-Expandable Devices for AS Patients at High-Surgical Risk in Japan Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan、2）Minimally Invasive Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan、 3） Department of Cardiology, Osaka University Graduate School of Medicine, Osaka, Japan 1） TAVI has recently been focused as a minimally invasive treatment for AS patients. After the approval of Edwards SAPIEN XT on October 2013, TAVI procedures are rapidly increasing also in Japan. In our institute, TAVI has aggressively been indicated for high-surgical risk patients with AS, so we reviewed clinical eﬃcacy of TAVI with the balloon expandable devices. Our heart team performed 192 TAVI to date, and Edwards SAPIEN valves were used in 141 cases（excluding 6 cases with 20mm prostheses）. The mean age of the cohort was 82.4 years. Eighty-nine patients（63%）were female. All patients had symptomatic severe AS with STS mortality risk of 12%. Optimal approaches were comprehensively selected case by case, considering anatomical condition of access route and aortic root complex.As a result, procedural success was achieved in all cases except one. Thirtyday and hospital mortality indicated 1.4% and 2.1%, respectively. The incidence of major intraoperative complications including coronary obstruction was 9.6% Strokes with obvious disablement occurred at the rate of 1.7%. Echocardiography revealed improvement of the aortic valve stenosis in all patients. The actuarial survival rate at one and three year after operation is 89% and 72%, respectively. In conclusion, despite of an issue of cost-beneﬁt and unknown long-term outcomes, TAVI would be promising alternative for high-risk AS patients. Percutaneous Mitral Valve Repair with The Mitraclip System for Patients with Functional Mitral Regurgitation Takashi MATSUMOTO Cardiovascular Center, Sendai Kousei Hospital Functional mitral regurgitation（MR）is commonly seen in patients with left ventricular dysfunction, and even if mild, is associated with limited quality of life and worsened mortality. As mechanical solution for functional MR, mitral valve （MV） surgery is eﬀective to reduce functional MR and improve quality of life. However, this has been underutilized because of a lack of evidence for survival beneﬁt and high risk features of the target patient population. Percutaneous MV repair with the MitraClip system（Abbott Vascular, Menlo Park, CA）is a catheter-based therapy to treat moderate to severe or severe MR. This novel device demonstrated comparable improvement of clinical outcomes as compared to conventional MV surgery, and had a better safety profile than surgery. Recent studies support the excellent safety proﬁle and potential clinical beneﬁt of the MitraClip procedure for patients with severe functional MR. In this presentation, I systematically review the current perspective of the MitraClip therapy for patients with functional MR. S05-4 Signiﬁcant Eﬃcacy of PTSMA for Drug Refractory HOCM Presenting Severe CHF Morimasa TAKAYAMA、Itaru TAKAMISAWA Department of Cardiology, Sakakibara Heart Institute Hypertrophic cardiomyopathy is mainly genetic disorder and 2/3 of patients develop intraventricular obstruction at rest or on provocation. Its symptomatic patients present exertional dyspnea, chest oppression and/or syncope. The advanced feature of left ventricular outflow or midventricular obstruction results in persistent dyspnea and restricts daily life significantly despite having normal or rather aggressive left ventricle. Exclusion of the obstruction had been achieved with surgical myectomy of interventricular septum, Morrow s operation, however undertaken rarely in Japan. Currently percutaneous alcohol septal myocardial ablation（PTSMA）has been introduced, and the fine procedure with super-selective contrast echo assessment provides amelioration of obstruction and symptomatic improvement even in NYHA 3-4 grade patients. Latest ACCF/AHA and ESC guideline include both surgical myectomy and PTSMA as "septal reduction therapy" as a recommended therapy for symptomatic patients. Our treatment series of the severe heart failure cases are presented and its issues will be discussed. 143 シンポジウム Kei TORIKAI1）、Toru KURATANI2）、Koichi MAEDA1）、Isamu MIZOTE3）、 Toshinari OHNISHI3）、Jota OHYABU3）、Yasuhiro ICHIBORI3）、 Satoshi NAKATANI3）、Yasushi SAKATA3）、Yoshiki SAWA1） S05-3 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S05-5 Eﬀects of Transcatheter Atrial Septal Defect Closure for Pulmonary Atrial Hypertension Yoichi TAKAYA、Teiji AKAGI、Yasufumi KIJIMA、 Koji NAKAGAWA、Shunji SANO、Hiroshi ITO Okayama University Hospital Objectives We aimed to assess the eﬀects of transcatheter atrial septal defect（ASD）closure in ASD patients with pulmonary arterial hypertension（PAH）. Methods Thirty-seven ASD patients with PAH who underwent transcatheter closure were enrolled. PAH was deﬁned as a mean pulmonary artery pressure（PAP） 25 mm Hg. Results As shown in Figure, systolic PAP improved signiﬁcantly at follow-up examination （57 to 35 mm Hg; p < 0.001）compared with baseline examination. The degree of improvement in systolic PAP was signiﬁcantly greater in patients receiving PAHspeciﬁc drugs therapy（n = 8）than in those not receiving these drugs therapy（n = 29）（47 vs. 18 mm Hg; p < 0.001）. Conclusions Transcatheter ASD closure was eﬀective for PAH. The combination of transcatheter closure and disease-targeted therapy may expand the therapeutic possibilities. シンポジウム 144 プログラム・抄録集シンポジウム６（S06）心不全における観察研究 S06-1 Observational Studies in Heart Failure Michel KOMAJDA Department of Cardiology and University Pierre et Marie Curie- IHU/ ICAN, Paris, France Observational studies are critical in chronic diseases such as heart failure in order to assess the management of this condition in real situation. Unlike clinical trials, patients enrolled in registries are not selected and are representative of the complexity of heart failure with usually multiple comorbidities. In addition, observational studies provide valuable information on the outcomes of heart failure, including death, cardiovascular death and rate of（re）hospitalizations. A uniform ﬁnding of registries is the fact that the rate of prescription of life saving medications is improving, whereas under dosage remains common. Geographic variations in the clinical profile and in the medical management of heart failure can be identified, the latter being the result of both economic conditions （aﬀordability）and medical traditions or culture. Due to huge diﬀerences in the organization of health care services across the globe, one critical factor to ensure representativeness of observational studies is the selection of centers where data collection is made（hospitals, emergency units, general practitioners…） In summary, observational studies are extremely important to conduct in order to assess whether international guidelines are implemented or not and, if not, to explore the reasons for the gap between guidelines and routine practice. S06-3 Japanese Cardiac Registry of Heart Failure in Cardiology（JCARE-CARD） Hiroyuki TSUTSUI Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan H e a r t f a i l u r e（ H F ）is a l e a d i n g c a u s e o f m o r t a l i t y and hospitalization for adults older than 65 years in the industrialized countries. The characteristics and outcomes of HF patients have been described by several epidemiological studies and large scale clinical trials, performed mainly in the United States and Europe, whereas very little information is available in Japan. The Japanese Cardiac Registry of Heart Failure in Cardiology（JCARECARD）prospectively studied the characteristics, treatment, and outcomes of a broad sample of patients hospitalized with worsening HF at teaching hospitals throughout Japan. Demographics, medical history, severity, treatment, and outcome data were collected and entered into a database via secure web browser technology. It enrolled 2,675 patients at 164 participating hospitals with an average follow-up of 2.2 years. It provided various important insights into the "realworld" characteristics, the prognostic predictors, and the improved management strategies of HF patients in routine clinical practice in Japan. S06-2 The Chronic Heart Failure Analysis and Registry in the Tohoku District（CHART） Study Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan The Chronic Heart Failure Analysis and Registry in the Tohoku District 2（ CHART-2）Study is one of the largest prospective observational multicenter cohort studies in Japan, designed to identify the characteristics, mortality and prognostic risks of patients with chronic heart failure（HF）and patients with cardiovascular disease（CVD）who are at high risk for development of de-novo HF. Between October 2006 and March 2010, a total of 10,219 patients with overt HF（Stage C/D）, structural cardiac disorder but without HF（Stage B）, or with coronary artery disease（ Stage A）were successfully enrolled, and are currently being followed-up. The mean patient age was 68.2± 12.3 years and male patients accounted for 69.8%. Overt HF was observed in 46.3% of patients（Stage C/D）,and 53.7% did not have HF but were at high risk for transition to de-novo HF（Stage A/B）. Compared with our previous CHART-1 study, the prevalence of ischemic etiology and cardiovascular risk factors, such as hypertension and diabetes, has increased, and prognosis has been improved along with implementation of evidence-based medications. Importantly, the trend of westernization of ischemic etiology was characterized mostly by an increase of patients with ischemic heart failure with preserved left ventricular ejection fraction. In this session, recent trends in the management and outcomes of CHF patients in the CHART studies will be presented. Observational Study on Heart Failure Using Failing Myocardial Samples Masanori ASAKURA1）、Hiroshi ASANUMA2）、Shin ITO1）、Kyung-Duk MIN1）、 Osamu SEGUCHI1）、Mitsuhiro NISHIGORI1）、Takeshi NAKATANI1）、 Takeshi TOMONAGA3）、Naoto MINAMINO1）、Masafumi KITAKAZE1） Department of Clinical Medicine and Development、2）Kyoto Prefectural University of Medicine, Kyoto, Japan、3）National Institute of Biomedical Inovation 1） The number of patients with heart failure is increasing with the aging of society. Patients with heart failure receive a variety of medications for heart failure such as human atrial natriuretic peptides, renin-angiotensin inhibitors, beta blockers, and aldosterone antagonists. Serelaxin, recombinant human relaxin-2, has recently been developed as a promising candidate drug for acute heart failure. Despite the progress of treatments for heart failure, poor prognosis of patients with heart failure is still a big issue. To solve this issue, we need to identify novel therapeutic targets for heart failure. We have searched for target molecules of heart failure using omics analyses of human, canine or murine failing myocardium. We found mitochondrial tumor suppressor 1 gene as a novel inhibitory factor against cardiac hypertrophy using exon array analysis of murine pressure-overloaded hearts. We have also searched for potential diagnostic targets for heart failure using proteomic analyses of canine failing hearts induced by high frequency pacing. Moreover, we have compared three omics data of failing myocardium from patients with dilated cardiomyopathy. These observational studies using transcriptomic, proteomic, and epigenomic analyses might provide novel targets for the development of novel therapies as well as biomarkers for heart failure. 145 シンポジウム Yasuhiko SAKATA、Kotaro NOCHIOKA、Masanobu MIURA、 Soichiro TADAKI、Ryoichi USHIGOME、Takeshi YAMAUCHI、 Jun TAKAHASHI、Satoshi MIYATA、Hiroaki SHIMOKAWA S06-4 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S06-5 Evidence of the Biomarkers From the Sub-Analysis Data of Clinical Trials and Registries Yukihito SATO Division of Cardiovascular Medicine, Hyogo Prefectural Amagasaki Hospital, Amagasaki, Japan Biomarkers are substances derived from organs, which can be measured and evaluated as indicators of normal biology, pathogenic process or pharmacological response to a therapeutic intervention. Their measurements is not subject to inter-observer variability. An ideal biochemical marker should be a prognostic indicator, assist in the early diagnosis of heart failure（ HF）, reliably reflect the therapeutic response, and help grading the risk associated with each stage of HF. While several biochemical markers have been studied for their prognostic value in the setting of chronic and acute HF, their clinical applications have not been systematically discussed. Moreover, change of ideal biomarkers should correlate the change of cardiovascular events. The relationship between cardiac remodeling and these biomarkers also should be elucidated. Finally, an ideal biochemical marker should be applicable to patients at the risk stage of HF. Biomarkers, such as CRP, BNP, collagen marker and high sensitive cardiac troponin has been reported as a prognostic marker of cardiovascular events in general population. In this symposium, we review biomarkers from the sub-analysis data of clinical trials and registries from, risk stage to overt HF. シンポジウム 146 プログラム・抄録集シンポジウム７（S07）チーム医療 S07-1 尼崎病院心不全チームにおける慢性心不全看護認定看護師の役割鷲田幸一兵庫県立尼崎病院尼崎病院では医師・看護師・心臓リハビリテーションスタッフ・理学療法士・管理栄養士・薬剤師の多職種で心不全チームを形成し、多職種での心不全患者の支援を行っている。2010 年から多職種心不全カンファレンスを開催し、心不全に対する知識や見解、課題を多職種で共有することから始め、心不全患者の問題に対して多職種で支援を行うことが可能となってきた。2012 年には慢性心不全看護認定看護師（CHFCN）が誕生し、2014 年から心不全看護外来を開設し、心不全チームの中で新たなポジションも出来た。心不全増悪を繰り返すコントロール困難な心不全症例や、終末期に向かう心不全患者の緩和ケアにおいて多職種支援の有効性を感じている。症例から見えてくる重要な点としては、多職種が同じ課題を認識し同じ目標に向かい支援することであり、また同時に各職種が専門性を保持しながら多面的に介入できるよう役割調整をし、包括的な支援を実現することである。そのために CHFCN が果たす役割と課題を提示し、多職種心不全チームの可能性と今後 CHFCN に期待される役割を検討したい。 S07-2 心不全チーム医療における医師の役割 ―チームのキャプテンに必要なものとは― 西裕太郎循環器診療におけるチーム医療は、外科手術や PCI、カテーテルアブレーション、デバイス治療さらには TAVI など専門性の高い治療手技に特化したチームと心臓リハビリテーションや栄養サポートチームなどの多職種協働型のチームがある。専門治療において医師は術者であり適応を判断し予後とリスクを説明し手技を施行して結果に責任を持つ。多職種協働チームでは医師は各職種がそれぞれの専門性を発揮できるようコミュニケ―ションと情報共有を行う。しかし心不全治療チームでは病期が進行すると専門治療と多職種協働介入によっても改善せず重症度が増し end-stage となる。ここで求められているのは治療のターゲットが予後改善の治療から症状緩和あるいは患者ニーズへの対応へシフトしていく過程での意思決定プロセスへの関与と具体的な症状への対応である。そこでは倫理的問題点の把握、患者・家族と向き合う自覚と意思決定を支援するコミュニケーション能力、緩和医療の知識と経験、チーム内での合意形成を導く方法の獲得、そして結果に対する責任が求められている。これらが循環器医にとって不可欠なものになりつつある。心不全在宅医療における多職種の役割弓野大、星敬美、伊東紀揮、吉田真希、堀部秀夫ゆみのハートクリニックこれからの心不全医療の新しいかたちとして、「心不全の在宅医療」が挙げられる。心不全の在宅医療の意義は、長期入院から在宅へ、再入院予防、急性増悪時の治療、在宅での看取りまでを行うことにより、生活を途絶することなく、在宅の場で生活の質を保ちながら療養を継続できることにある。在宅の場では、ひとりの患者に対して、家族、訪問診療医、訪問看護師、ソーシャルワーカー、ケアマネージャー、訪問理学療法士、訪問薬剤師、介護ヘルパー、民生委員など多施設多職種での関わりが必要であり、それぞれの疾患に対する知識の差が、患者のとらえ方に相違を生じさせている。多施設多職種間のコミュニケーションが患者の在宅療養継続のポイントであると捉え、当院では多職種症例カンファレンスの定期開催とコミュニケーションツールの開発を行っている。本セッションでは、心不全の在宅医療に関わる職種の役割について、ひとつの症例への個々の職種からのアプローチを複合交差体として表し、これからの心不全医療の発展に寄与することができるよう議論したい。 S07-4 心不全のメンタルヘルスケア-心理士の立場から庵地雄太 1,2）、水谷和郎 1）、菅野康夫 2）、安斉俊久 2） 1）神戸百年記念病院心大血管疾患リハビリテーションセンター、2）国立循環器病研究センター心臓血管内科部門心不全治療は日々進歩を続けているが「心（こころ）」不全への対応は広がっているのであろうか。循環器領域に従事する医療者は心不全患者へのメンタルヘルスケアの必要性を認識している。しかし、未だ十分なケアが実践されていない。その理由としてマンパワー不足、診療報酬の未確立、医療者側の不安などが挙げられる。平成 24 年、身体疾患患者へのメンタルヘルスケアを推進する国家プロジェクトが立ち上がった。その一環として兵庫サイコカーディオロジー研究会が設立。循環器疾患患者へのメンタルヘルスケア推進に取り組んでいる。神戸百年記念病院では心理士を常勤採用し、3 年間で 150 例以上の心疾患患者にメンタルヘルスケアを実践してきた。また、国立循環器病研究センターに本邦初となる循環器緩和ケアチームが誕生し、先天性心疾患患者や移植待機患者など幅広い心疾患患者にメンタルヘルスケアを行っている。メンタルヘルスケアの課題をどのように解決してゆけばよいのか。どうすれば「心」不全へのケアが広がってゆくのか。今回、心理士の立場から心不全患者へのメンタルヘルスケアの実践報告を行い、多くの示唆を得ると共に啓蒙・啓発につながることを期待する。 147 シンポジウム聖路加国際病院心血管センター循環器内科 S07-3 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S07-5 栄養サポートにおけるチーム医療の変革と将来宮澤靖社会医療法人近森会近森病院臨床栄養部少子高齢社会を迎え、医療現場では若くて元気な患者の減少とともに高齢者が急激に増加している。高齢患者の特徴は、低栄養や廃用、認知症であり、栄養とリハビリテーション、医療安全などのチーム医療を実践する必要性が高くなっている。栄養サポートは、食べるという人間として最も基本的な行為によって摂取されるものであり、医師、看護師はじめ多職種が取り組みやすく、すぐに結果が現れ、チーム医療の効果や良さが理解されやすいという利点を持っている。したがって栄養サポートチームを実践し、チーム医療が病院を変えるということを実感しやすいと思われる。しかしながら本来のこのような実感がないと感じるチームが多いのが現状であると思われる。それは「チーム医療」という概念が以前と違ってきていることと、各専門職種の業態の変化ならびに医療変革によるものと思われる。高齢化社会を迎えた本邦において、循環器系疾患が死因別疾患で第2位となってしまった。急性期、慢性期を問わず、チーム医療の概念を変え、仕組みを変えて各専門職種の能力を最大限に引き出すためにはどのような取り組みや意識改革が必要なのか当院の 10 年間の取り組みを元に検証する。シンポジウム 148 プログラム・抄録集シンポジウム８（S08）心不全における先進医療 S08-1 Gene Therapy for Heart Failure Roger J. HAJJAR Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai School, New York, NY One of the key abnormalities in both human and experimental heart failure（HF）is a defect in sarcoplasmic reticulum（SR）function. Deficient SR Ca 2+ uptake during relaxation has been identified in failing hearts from both humans and animal models and based on the ﬁndings that the SR Ca 2+ ATPase（ SERCA2a）expression and activity are decreased in HF and that gene transfer of SERCA2a improves key parameters of HF, our group launched the first clinical gene therapy trial in patients with HF using adeno-associated vectors（ AAV）. CUPID（Calcium Up-Regulation by Percutaneous Administration of Gene Therapy in Cardiac Disease）was designed to evaluate the safety proﬁle and the biological eﬀects of gene transfer of the SERCA2a cDNA by delivering a recombinant AAV1 （AAV1.SERCA2a）in patients with advanced HF. AAV1. SERCA2a treated patients, versus placebo, demonstrated improvement in multiple clinical parameters and in NYHA , VO2 max, NT-proBNP class, 6MWT（six minute walk test） levels, and left ventricle end-systolic volumes. Further clinical studies are now underway including an international study in 250 patients, testing whether AAV1.SERCA2a （1 x 1013 DRP）versus placebo, randomized 1:1, is an eﬀective therapy to reduce cardiovascular events in advanced HF. Furthermore, the recent success of the phase 1 and Phase 2 CUPID trials usher a new era for gene therapy for the treatment of heart failure. S08-2 A New Evaluation Method for Reverse Remodeling Viability of Heart Failure Machiko KANZAKI、Yoshihiro ASANO、Yasushi SAKATA Numerous studies tried to solve the pathophysiology of heart failure, but we can hardly know the point of no return in developing heart failure. If we can succeed in predicting the future prognosis of heart failure in the early stage, the earlier interventions might reduce the risk of cardiac death, propose acceptable therapeutic option, and improve a quality of life in the heart failure patients. If we intend to know the start point of the one-way deterioration, we have to catch the upstream of terminal phenotype. We have to catch the upstream of increasing fibrosis, the upstream of cell death, and, therefore, the upstream of gene expression changes. As the accumulating stress for gene expression can affect the epigenetic status and chromatin structure, we hypothesized that progression of heart failure might related to alter chromatin structure in cardiomyocytes' nuclei. Thus we aimed to design the pathophysiological study making a quantitative evaluation of the chromatin structure. In the present study we established the original method for automatic calculation of nucleic chromatin structure by electron microscopic analysis. We could clearly distinguish which group can avoid VAD implantation within 12 months after the biopsy in iDCM patients.We would like to discuss about the importance of the evaluation of chromatin structures for early prediction of poor outcome in patients with iDCM. Drug Discovery Against Heart Failure Using Human Ips Cells Atsuhiko NAITO Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan Heart failure is a clinical syndrome that occurs when the heart is unable to ﬁll and/or eject blood suﬃciently. Advances in molecular biology and gene targeting technology lead to the discovery of new eﬀective drugs against certain diseases, however, current pharmacotherapy against heart failure is limited to diuretics, renin-angiotensin-aldosterone axis inhibitors, βadrenergic receptor antagonist, whose effect was already proved in 1980's, suggesting the requirement of a "paradigm shifting" strategy for new drug discovery against heart failure. Induced pluripotent stem（iPS）cell technology is considered to provide a breakthrough to many research ﬁelds including drug discovery. Drug screening using human iPS cell-derived cells, is advantageous over traditional drug screening because we can observe the native molecular and physiological response against various molecules in the cell type of interest. We may also recapitulate the 'disease-phenotype' using iPS cells established from the patients of certain hereditary diseases and construct a phenotype-based screening system to discover a new drug against those diseases. We are currently conducting a national project "The Program for Intractable Diseases Research utilizing Disease speciﬁc iPS cells". Thanks to the help from the colleagues in the Japanese Heart Failure Society, we have successfully established many iPS cell lines mainly from the patients of cardiomyopathy. Today, we will introduce our approach toward new drug discovery against cardiomyopathy and heart failure beyond. S08-4 Current Perspectives on Cardiac Regenerative Therapy with Human Induced Pluripotent Stem Cells Jun FUJITA Department of Cardiology, Keio University School of Medicine, Tokyo, Japan Heart failure（HF）is the leading cause of death in developed countries. Heart transplantation is the only radical treatment of severe HF; however, donor shortage remains an unsolved problem. Induced pluripotent stem cell（iPSC）generation is a revolutionary technology as an infinite cell source for cardiomyocytes（CM）. Therefore regenerative medicine with iPSCs has promised to fulﬁll this unmet medical need. However, clinical application of iPSCs needs to be achieved step by step. The establishment of safe iPSCs in xeno-free condition must be a first step, while genome integration-free and oncogene-free reprogramming is necessary. Cell culture systems for massive amount of both undiﬀerentiated iPSCs and diﬀerentiated CM are also essential, because an adult heart contains more than 1x109 CM. Tumorigenicity is another potential of undifferentiated iPSCs. It will be a great tragedy, if it happens in a patient's heart. Thus, the diﬀerentiated CM from iPSCs must be puriﬁed to exclude any possibility of tumorigenicity. The transplantation strategies used for iPSC-derived CM are very important for the recovery of lost cardiac function. Preclinical studies with large animal models, such as pigs, must be performed to verify the safety and efficacy of iPSCs-derived CM transplantation. Feasible and carefully optimized techniques for each stage must inevitably be established to realize regenerative therapy for advanced HF using iPSC-derived CM. 149 シンポジウム Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan S08-3 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S08-5 Epigenetic Therapy as a Potential Novel Treatment for Chronic Heart Failure Ruri KANEDA、Tomohiko ONO、Keiichi FUKUDA Department of Cardiology, Keio University School of Medicine The evidences for a role of epigenetic regulation in the development of hypertrophy, contractility, energy metabolism, and fibrosis in the heart have been recently reported. On the treatment, HDAC inhibitors have been focused as valuable drugs for heart disease. We previously demonstrated that the distribution of H3K9me3 in the failing heart is quite different from that in control hearts both in animal models and clinical heart specimens. Therefore we focused on this heart failure-speciﬁc histone modiﬁcation and investigated the prognostic eﬃcacy of administering a histone H3K9 methyltransferase inhibitor, Chaetocin, to Dahl saltsensitive rats, an animal model of heart failure. Chaetocin has delayed the timing of transition from cardiac hypertrophy to heart failure and prolonged survival term in the animal model. The mitochondrial dysfunction was improved with inhibitor use in the failing heart. In ChIP-seq analysis, at 7,326 loci associated with repetitive elements, including regions neighboring mitochondrial genes, heart failure caused an increase in H3K9me3 alignments and a corresponding reduction with inhibitor use. At only 21 loci, heart failure was associated with a reduction in H3K9me3 alignments, and an increase with inhibitor use. These data suggest that excessive heterochromatinization of repetitive elements in the failing heart might impair pumping function via silencing of mitochondrial genes. H3K9 methyltransferase inhibitor may have promise as a novel therapy for chronic heart failure. シンポジウム 150 プログラム・抄録集シンポジウム９（S09）重症心不全の診断および治療戦略 S09-1 S09-3 Risk Stratiﬁcation in Patients with Chronic Heart Failure Using Cardiac Sympathetic Imaging with MIBG Immunomodulatory Therapy for Patients with Refractory Heart Failure Due to Dilated Cardiomyopathy Takahisa YAMADA、Shunsuke TAMAKI、Masatake FUKUNAMI Tsutomu YOSHIKAWA1）、Akiyasu BABA2）、Hitonobu TOMOIKE1） Division of Cardiology, Osaka General Medical Center 1） Sakakibara Heart Institute, Fuchu, Japan、 2）Cardiology, Kitasato Institute Hospital Despite recent advances in pharmacolocigal and nonpharmacological treatment, mortality and morbidity remains high in patients with chronic heart failure（CHF）. The risk stratification by predicting poor outcomes in patients with CHF can help physicians guide therapy. In CHF, cardiac sympathetic nerve overactivity contributes to the progression of the disease and is associated with poor outcomes. Cardiac MIBG sicntigraphy is the only one of an imaging tool to estimate cardiac adrenergic nerve function, and provides valuable information about the evaluation of CHF severity, the monitoring of clinical course and response to therapy, and prognosis. The prediction of sudden cardiac death（SCD）remains an important goal in CHF patients. We previously reported that cardiac MIBG imaging could be useful for the prediction of SCD in CHF patients and that MIBG imaging would also be a powerful predictor of SCD, compared with electrocardiographic parameters such as signal-averaged ECG, heart rate variability and QT dispersion. Furthermore, the combination of MIBG imaging and the clinical risk score such as Seattle Heart Failure Model could identify the subset at higher risk of poor outcomes in CHF patients. Recently, the large-scaled multicenter studies have provided the validation of the independent prognostic value of cardiac MIBG imaging in assessment of CHF patients. Cardiac MIBG imaging is reconﬁrmed to be a useful tool to risk stratify CHF patients. S09-2 Autoimmune abnormalities appear to be one of the predominant underlying disorders, as well as genetic abnormalities and acquired infection for the development of dilated cardiomyopathy（DCM）. Various antimyocardial antibodies are detected in the serum of patients with DCM. Recent findings have suggested that at least some of them are directly related to the pathophysiology of DCM. Immunoadsorption technique（IA）is one of the potentially promising therapeutic measures to remove these autoantibodies. As a proof of concept study, IA therapy was conducted in 16 patients with DCM（NYHA functional class III/IV, mean ejection fraction 18±2%）using a IgG-3 subclassspeciﬁc tryptophan column. Study subjects had autoantibodies directed against either β1-adrenergic or M2-muscarinic receptors. IA was performed for 1.5 hours each session, and repeated 3 to 5 times. IgG-3 subclass was removed to greater extent than other subclass as expected. Left ventricular ejection fraction measured by radionuclide ventriculography signiﬁcantly increased over the 3 months after completion of IA. Clinical trial comparing 5 times sessions and 10 times sessions has been completed, and awaits analyzing dataset. Conclusions: Our initial experience demonstrated safety and short-term efficacy of IA using a novel IgG3-speciﬁc tryptophan column for patients with advanced heart failure due to DCM. This therapy may be one of the options to rescue refractory heart failure due to DCM. S09-4 Current Status of Heart Transplantation in Japan Tsuyoshi SHIGA Koichiro KINUGAWA Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan The Department of Therapeutic Strategy for Heart Failure, The University of Tokyo, Tokyo, Japan The treatment goals for patients with severe heart failure are to improve prognosis and quality of life. Sudden cardiac death （SCD）, which is primarily caused by ventricular tachycardia （VT）/ﬁbrillation（VF）, accounts for approximately one-third of all deaths in heart failure patients. Therefore, the prevention of VT/VF is a key issue in the treatment of these patients. Immediate defibrillation by DC shocks is mandatory for the treatment of VT/VF associated with serious hemodynamic deterioration. If arrhythmia persists after several DC shocks, amiodarone or nifekalant is given intravenously. Atrial ﬁbrillation（AF）frequently occurs in patients with severe heart failure. It is recognized that AF leads to clinical deterioration and, even worse, heart failure. AF also increases the risk of mortality and morbidity in heart failure patients. Persistent AF in hemodynamically unstable patients should be promptly cardioverted. Amiodarone appear to be eﬀective for the strategy of maintenance of sinus rhythm in heart failure patients with AF. The mechanisms of arrhythmias associated with heart failure are complex and heterogeneous; they include functional and structural remodeling, as well as neurohormonal activation. Basic drug therapy, beta-blockers and angiotensin-converting enzyme inhibitors, and antiarrhythmics such as amiodarone prevent arrhythmias and SCD. Recently, there has been much progress with the catheter ablation technique, implantable cardioverter-defibrillators, and cardiac resynchronization therapy devices, which are now useful in selected patients. Heart transplantation（HTx）and durable ventricular assist device（VAD）are options to improve long-term survival of stage D heart failure patients. VAD can extend patients' survival with considerable improvement of quality of life, but there is some limitation for patients with VAD implantation in terms of daily life. In this regard, HTx is the only therapeutic tool to restore virtually normal daily life. However, in Japan, there are severe donor shortage even after the amendment of organ transplant law since 2010. If the current number of annual donors continues, total status 1 patients on waiting list might be more than 300 in several years, and as a result waiting period must be over 7 years. I will discuss how to manage stage D HF patients with mechanical assist device in such a tough situation, and also would like to propose to limit HTx eligibility with expansion of VAD indication. 151 シンポジウム Management of Arrhythmias in Severe Heart Failure 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S09-5 Role of Implantable LVAD as an Important Platform for End-Stage Heart Failure Koichi TODA、Teruya NAKAMURA、Shigeru MIYAGAWA、 Yasushi YOSHIKAWA、Satsuki FUKUSHIMA、Daisuke YOSHIOKA、 Tetsuya SAITOU、Takayoshi UENO、Touru KURATANI、Yoshiki SAWA Department of cardiovascular surgery, Osaka University, Osaka, Japan Objective: Mechanical circulatory support with an implantable left ventricular assist device（ LVAD）plays an important role in the treatment of end-stage heart failure patients waiting for heart transplantation. We reviewed our experiences of LVAD implantation to investigate their clinical impact in comparison with conventional surgery including surgical ventricular reconstruction （SVR）.Methods: Between 2005 and 2014, 86 consecutive patients with end-stage heart failure were supported by continuous flow implantable LVADs. During the same period 61 patients underwent SVR.Results: Preoperatively LVAD patients were younger and were more dependent on inotropic support. 30 days mortality was 1（1%）and 1 and 2 years survival was 95% and 85%, respectively in LVAD group. SVR group demonstrated signiﬁcant cardiac reverse remodeling indicated by reduction in LVESVI and increase in LVEF. One and 2 years survival after SVR was 82% and 68%, respectively and multivariate analysis identified preoperative pulmonary hypertension and LVESVI>150 ml/ m2 were signiﬁcant predictors of recurrence of heart failure in SVR group. Conclusions: Our results demonstrated good survival in LVAD patients who were young enough to be a candidate for heart transplantation. Selected patients among the patients who underwent SVR might have had survival beneﬁt by LVAD implantation or LVAD may provide us an important back-up for recurrent heart failure after conventional surgical approach. シンポジウム 152 プログラム・抄録集シンポジウム１０（S10）二次性心筋症（サルコイドーシスや緻密化障害など） S10-1 S10-3 Clinical Pictures of 134 Cases of Cardiac Sarcoidosis: A Multi-Institutional Study Hypertrophic Cardiomyopathy and Syndrome with LV Hypertrophy Shinichiro MORIMOTO1）、Hiroyuki TSUTSUI2）、Masahumi KITAKAZE2）、 Kengo KUSANO2）、Yoshikazu YAZAKI2）、Akihito TUCHIDA2）、 Fumio TERASAKI2）、Yoshio ISHIDA2）、Takatomo NAKAJIMA2）、Mitsuaki ISOBE2） Hiroaki KITAOKA、Toru KUBO、Yuichi BABA、 Naohito YAMASAKI Aoyama General Hospital, Aichi, Japan、 2）The Japanese Cardiac Sarcoidosis Research Group, Tokyo, Japan 1） [Aim] Cardiac sarcoidosis is a relatively rare disorder, the clinical pictures of which have not yet been adequately clarified. Also, although recently the existence of isolated cardiac sarcoidosis has been described, much remains to be learned about its details. [Method] We retrospectively investigated 134 cases of cardiac sarcoidosis from 9 institutions, and analyzed their clinical pictures.[Results] The 134 cases comprised a histologic diagnostic group of 61 cases（45.5%）, clinical diagnostic group 51 cases（38.1%）, isolated cardiac cases 17 cases , and a suspicious group 5 cases（3.7%）. Serum ACE levels were abnormally elevated in 38.3% of cases, while on myocardial biopsy noncaseous epithelioid cell granulomas were observed in no more than 26% of cases, similar to the results of previous investigations. On echocardiography, basal thinning of the interventricular septum was noted in 55 cases （41%）, with thinning found at other sites of the ventricular wall such as the inferior wall and posterior wall in 12 cases （9%）as well. On echocardiography, wall motion abnormalities were found in 63.2% of cases, and ventricular aneurysm in 5.6%. On Ga scintigraphy, accumulation in the heart was present in 46.2% of cases, whereas it was much higher, 85.2% of cases, on FDG-PET. Furthermore, on gadolinium-enhanced cardiac MRI, delayed myocardial enhancement was seen in 92.4% of cases. S10-2 Department of Cardiology, Neurology and Aging Science, Kochi Medical School, Kochi University Hypertrophic cardiomyopathy（HCM）is a common genetic cardiac disease that is mainly caused by sarcomeric protein mutations. Although the prognosis of HCM is various, sudden cardiac death, heart failure and embolic event mainly due to atrial fibrillation are important through whole life. Therefore, appropriate interventions are needed according to clinical stage of disease. Another important issue is distinguished syndrome with left ventricular hypertrophy such as mitochondrial disease, Fabry disease or storage disease from HCM. In particular, Fabry disease is important, because the eﬀective therapy such as enzyme replacement therapy has been progressed and the improvement of prognosis is expected.In this part, I would like to have a talk in those points of view. S10-4 The Problem of Diagnostic Delay of Fabry Disease Jun KOYAMA、Masatoshi MINAMISAWA、Ayako OKADA、 Hirohiko MOTOKI、Yuuji SHIBA、Atsushi IZAWA、 Yusuke MIYASHITA、Uichi IKEDA Taiki HIGO Department of Cardiovascular Medicine, Shinshu University School of Medicine, Matsumoto, Japan Background: Prognostic impact of regression of left ventricular noncompaction appearance after optimal treatment in adult patients with left ventricular noncompaction cardiomyopathy（ LVNC）is poorly understood. Methods and Results: Among 300 patients with non-ischemic dilated cardiomyopathy, we identiﬁed 23（7.7%）patients who fulﬁlled echocardiographic criteria of LVNC. We prospectively examined these 23 concecutive patients with LVNC. All patients underwent serial echocardiography. LV reversal remodeling （RR）was defined as an absolute increase in LV ejection fraction （EF）more than 10% at 6 months after optimal medical therapy and/ or device therapy. LV noncompaction areas were calculated as the subtraction from the outer edge to the inner edge of the LV noncompaction area at end systole. The mean follow-up period was 54 months（range from 10 to 97 months）. LVRR by our deﬁnition was observed in 9 patients（39.1%）at 6 months. The changes in the LV non-compaction area showed signiﬁcant corelation with the changes in LVEF（r=-0.78, p<0.0001）and LV global longitudinal strain （r=0.61, p<0.002）. In Kaplan-Meier analysis, cardiac death occurred in 7 patients（50%）in the non-LVRR group and in no patients in the LVRR group（P = 0.003）. Conclusions: Regression of LVNC appearance is associated with the improvement of LV systolic function. The high adverse outcome rate in non-LVRR necessitates early recognition and appropriate therapeutic intervention. Cardiovascular Medicine, Kyushu University Hospital Fabry disease is one of genetic disorders which involve multi-organ system such as heart, kidney, and brain. It is caused by genetic deficiency of alfa-galactosidase A which transmitted through an X-linked gene. Clinical characteristics of Fabry disease often mimic those of hypertrophic cardiomyopathy（HCM）and often be misdiagnosed. However, recent approved alfa-galactosidase enzyme replacement therapy would enable to prevent the progression , or regression in somce cases, of organ damages if the patient is diagnosed earlier. In that point of view, the major problem concerning management of Fabry disease is the diagnostic delay. It is reported that it tends to be more than 10 years before Fabry disease patients are correctly diagnosed since the characteristic symptoms appeared. It is very important for us to be more familiar with early signs and symptoms of Fabry disease, and to make a screening of Fabry disease in patients suspected of HCM as well. Moreover, when a certain patient is diagnosed as Fabry disease, family screening will enable early diagnosis of new patients. The earlier the diagnosis of Fabry, the more eﬀective the enzyme replacement therapy would be. Additionally, we should know that measuring enzyme activity is very useful screening way in making diagnosis of Fabry disease in male patients, but we should consider even genetic screening in making diagnosis with female patients. 153 シンポジウム Left Ventricular Noncompaction Cardiomyopathy in Adult 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S10-5 Peripartum Cardiomyopathy ∼Recent Results of Basic and Clinical Research∼ Chizuko KAMIYA Perinatology and Gynecology Department, National Cerebral and Cardiovascular Center, Osaka, Japan Peripartum cardiomyopathy（PPCM）is a rare disease that occurs during pregnancy, and up to 5 months postpartum, in previously healthy women. Early signs and symptoms of PPCM, including dyspnea on exertion, peripheral edema, and body weight gain, may often mimic normal physiological findings of pregnancy. Therefore, early diagnosis is sometimes difficult. Advanced maternal age, pregnancy-related hypertension including preeclampsia, twin pregnancy, and tocolytic therapy are known as risk factors of PPCM. In order to prevent severe heart failure and maternal death, peripartum women with the above risk factors should be observed cautiously and must immediately undergo a cardiac examination as needed.Although its etiology remains unknown, recent ﬁndings have suggested that an increase in oxidative stress may aggravate the proteolysis of full-length prolactin, and anti-angiogenic prolactin fragments, called prolactin-related vasoinhibin, may subsequently contribute to the deterioration of PPCM. Therefore, anti-prolactin therapy（APT）, which suppresses the secretion of prolactin through the administration of a dopamine agonist such as bromocriptine, was introduced as a novel and disease-speciﬁc treatment for PPCM. From the results of a Japanese nationwide prospective survey, which is a prospective and observational study, APT showed more improvement of cardiac function in the acute phase, but did not change left ventricular ejection fractions after 1 year. S10-6 Diagnosis and Management of Takotsubo Cardiomyopathy Satoshi KURISU、Yasuki KIHARA シンポジウム Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan Takotsubo cardiomyopathy has become accepted worldwide as a distinct clinical entity since the first report by Sato et al in 1990. Takotsubo cardiomyopathy usually occurs in postmenopausal elderly women, and is characterized by chest symptoms, electrocardiographic changes and transient left ventricular apical wall motion abnormalities after emotional or physical stress. In the clinical setting, takotsubo cardiomyopathy is an important disease which should be differentiated from acute myocardial infarction promptly for the appropriate management. Left ventricular apical wall motion abnormalities are usually resolved during a period of days to weeks, and the prognosis is generally favorable. However, several acute complications have been reported such as congestive heart failure, cardiac rupture, left ventricular apical thrombosis or arrhythmias. Monitoring clinical course is essential to prevent or treat acute complications. Several possible mechanisms including multivessel coronary artery spasm, coronary microvascular dysfunction and catecholamine toxicity have been proposed to explain takotsubo cardiomyopathy, but its pathophysiology is not well understood. It is necessary to clarify the precise pathophysiology for establishing the optimal management of takotsubo cardiomyopathy. We will summarize the current knowledge on the diagnosis and management of takotsubo cardiomyopathy. 154 プログラム・抄録集シンポジウム１１（S11）臨床研究を真に志す人のために S11-1 New Regulatory System for Clinical Research in Japan Yasuhiro FUJIWARA Strategic and Planning Bureau, National Cancer Center The Ethical Guidelines for Epidemiological Research （initial release 2002）and the Ethical Guidelines for Clinical Research（initial release 2003）, both of which relate to public health and medical research, are revised every five years. Concerned parties raised the need to coordinate these two guidelines, pointing out that recent multi-faceted advances in health research have complicated the distinction between them. Then, MEXT and MHLW launched a joint revision committee in February 2013. Meanwhile, the discovery of data manipulation in the clinical trials of valsartan, the hypotensive agent marketed by Novartis Pharma, triggered the establishment of the MHLW Committee on Clinical Research of Antihypertensives（ August 1, 2013）. This committee released its oﬃcial report in April 2014. With these events as a backdrop, the Joint MEXT and MHLW committee announced a draft version of the Ethical Guidelines for Human Medical Research in May 2014.The new guideline consists of nine chapters: Chapter 1 General provisions; Chapter 2 Researcher responsibilities; Chapter 3 Study protocol; Chapter 4 Institutional review board; Chapter 5 Informed consent ; Chapter 6 Personal information; Chapter 7 Management of serious adverse events; Chapter 8 Quality assurance; Chapter 9 Miscellaneous provisions. Most notable section is Chapter 8 for preventing data fraud; the principal investigator of a study involving invasive procedures（excluding negligibly invasive techniques）will be subjected to monitoring and auditing. S11-2 S11-3 Amendment of Pharmaceutical Aﬀairs Law 山下雄大厚生労働省医薬食品局審査管理課医療機器・再生医療等製品審査管理室 Based on the amendment of Pharmaceutical Affairs Law （PAL）which is to be implemented on 25 November 2014, the Ministry of Health, Labour and Welfare is introducing regulations taking into account characteristics of medical device, which will result in acceleration of medical device marketing under more rational regulations. The name of PAL is changed to "Act on Securing Quality, Eﬃcacy and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics（PMD Act）". This change intends to clarify the scope of PMD Act includes medical device. S11-4 The Development of Cardiovascular Drugs in the Future Shoji SANADA Toshiki SUGITA Research and Development Division, Health Policy Bureau, Ministry of Helth, Labourand Welfare, Government of Japan Office of New Drug II, Pharmaceuticals and Medical Devices Agency, Tokyo, Japan In the major countries including Japan, each novel medical agents and technologies should undergo systematic validation of their safety and efficacy through the clinical trials under regulation of Pharmaceutical Affairs Law （PAL）before their practical labeled use with medical coverage. Currently, the Ministry of Health, Labour and Welfare of Japan（MHLW）is operating the Advanced Medical Service System that can serve as a qualified gateway into PAL-regulated clinical validation, through evaluating novel agents and technologies including Firstin-human use with specifically permitted clinical protocols under selective medical coverage. The MHLW permits currently 37 clinical trial protocols in some speciﬁc qualiﬁed institutes and with some operators respectively, which can evaluate targeted agents and technologies under offlabel use or beyond PAL permission. In this session, we will introduce how this system might practically work for supporting the establishment and PAL approval of novel medical agents and techniques, including introduction of some speciﬁc examples as well as current revolution of the system. Ministry of Health, Labour and Welfare（MHLW）released the guideline for clinical evaluation of drugs for heart failure on March, 2011. This guideline provides the standard procedure to conduct and evaluate non-clinical and clinical studies which are conducted for new drug application. Using this guideline, academia and venture companies as well as pharmaceuticals companies, will , increasingly, find opportunities for new drug development in future. However, even if academia and venture companies who have candidates of innovative drugs, they are not always familiar with regulatory system and drug development strategies. In order to create innovative drugs originating from Japan, Pharmaceuticals and Medical Devices Agency（PMDA）started new scientiﬁc consultation service, named 'Pharmaceutical Affairs Consultation on R&D Strategy' on July, 2011. This consultation system is mainly for academia and venture companies who has very progressive idea or studies, but little experience and knowledge about regulation. Through this consultation, the guidance and advice on non-clinical and early-stage clinical studies, which conform to pharmaceutical regulation, and ultimately determine the approval of submissions. As of March, 2014, a total of 307 Pre-consultations about drugs were carried out, and 50 of those were category 2 drugs （including cardiovascular drugs）. This system is expected to provide new, and eﬀective strategies for drug development, eventually leading to the approval of innovative products. 155 シンポジウム Current Status of Advanced Medical Service System in the Cardiovascular Field in Japan 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S11-5 The Outlook of the Cardiovascular Devices Development in the Future Mami HOU Pharmaceuticals and Medical Devices Agency A title of the the Pharmaceutical Affairs Law is changed to "a law about quality, effective and safe securing of the Pharmaceuticals and Medical Devices" by the amended Pharmaceutical Affairs Act, as revised in November 2013. The Ministry of Health, Labour and Welfare works on construction of the regulation on the basis of a characteristic of the medical devices. In a Japan revival strategy, the medical devices development is placed with the important policy. Innovative Japanese medical device development is expected, but there are many companies hesitating about development of expensive medical device of the novelty from the diﬃculty of corporate scale and the clinical trial. There are some problems in the clinical trial of the medical device, such as diﬃculty of blinded trial, physician s procedural technical bias which inﬂuence eﬀectiveness and safety. I think that we could design a feasible appropriate clinical trial if we narrow down the points which should be clariﬁed in clinical trial from evidence accumulated, and /or a non-clinical trial result. In the cardiovascular areas, medical device development aiming minimally invasive procedure as a substitute of the surgery, and improvements in quality of life is pushed forward. So, it is very important that the development strategy that fixed its eyes on approval application from an early stage. S11-6 我が国の循環器領域における臨床研究の将来宮田俊男日本医療政策機構シンポジウムアベノミクス第三の矢の目玉の一つとして、2015 年 4 月より日本医療研究開発機構が始動する。今後、基礎研究の成果について出口まで一貫した支援が期待される。 PMDA と連携した新しい評価方法を構築するためのレギュラトリーサイエンスも推進される。また健康・医療・介護領域において医療機関間のデータの共有化も進み、ビッグデータの活用も期待される。今後の我が国における循環器領域における臨床研究の将来について考えてみたい。 156 プログラム・抄録集シンポジウム１２（S12）心不全の分子メカニズム S12-1 S12-3 Small-Molecule Inhibitors of MAP4K4 Suppress Cardiac Muscle Cell Death Mitochondrial DNA as a scavenger of Mitochondrial ROS in Cardiac Remodeling Michael D. SCHNEIDER Tomomi IDE、Masataka IKEDA、Kenji SUNAGAWA Imperial College London, UK Kyushu University, Department of Cardiovascular Medicine, Fukuoka, Japan Strategies to rescue cardiac muscle cell number after ischemic injury potentially include suppressing cardiac muscle cell loss through next-generation methods to enhance cardiomyocyte survival. We have implicated the protein kinase MAP4K4 in cardiac muscle cell death, on the basis of diverse criteria including human tissue characterisation, gain-of-function mutations that mimic the activation seen in mouse and human heart disease, and cardioprotection in culture by MAP4K4 shRNA. Building on an initial screen and 3D field-point modeling, we have developed potent, specific, non-toxic hits that inhibiting only 3 to 5 out of >140 kinases, have in-cell activity against human MAP4K4, and confer protection to cardiac muscle cells in culture. Thus, MAP4K4 is a well-posed target for further drug development, towards proof of activity in an animal model of human heart disease. S12-2 Intra-Mitochondrial ATP Concentration Reﬂects The Cellular ATP Availability and Determines The Cardiac Contractility Department of Medical Biochemistry, Osaka Universtity Graduate School of Medicine, Osaka, Japan ATP is the main cellular energy source and is mostly generated by mitochondria. Heart muscle consumes large amount of ATP and its metabolism is known to be important for cardiac function. ATP depression caused by various diseases such as cardiomyopathy and ischemic heart disease leads to the decline of cardiac contractility. Cardiologists have investigated the ATP metabolism by measuring intracellular ATP concentration; however the precise evaluation of ATP availability remains diﬃcult. To overcome this diﬃculty, we developed the method of real-time measuring of the intramitochondrial ATP concentration（[ATP]mit）. Because there are no ATP buﬀering enzymes in the mitochondrial matrix, [ATP]mit well indicated the ATP production and availability. In fact the inhibition of ATP synthesis or the hypoxic condition rapidly decreases the [ATP]mit, while the cytosolic ATP concentration still remained normal. Using this method, we identified the novel molecules that increase the ATP production rate in cardiomyocytes. These molecules increase the ATP production in the hypoxic condition and preserve the cardiac contractility. In this symposium, I would like to discuss about the meaning of measuring ATP availability in the various pathological conditions of heart and the possibility of [ATP]mit modifying proteins as a therapeutic target for heart failure. S12-4 Nutrient Axis as a Pathophysiology of Heart Failure Tetsuo SHIOI Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan Hemodynamic system, sympathetic nervous system, renin angiotensin system, and natriuretic peptide system are important pathophysiology of heart failure, and these concepts have been valuable for elucidating the mechanisms, as well as diagnosis and treatment of heart failure. Heart failure is associated with changes in metabolism of heart, including substrate alteration, mitochondrial dysfunction, and decreased energy reserve. Heart failure is also associated with systemic metabolic abnormalities, such as insulin resistance and cachexia. In heart failure, decreased cardiac function limits the availability of nutrients of organs and modifies systemic energy metabolism. Recent experimental ﬁndings have suggested that systemic metabolic condition can modulate cardiac metabolic condition, as well as cardiac function. Thus, a vicious cycle that decreased cardiac output causes systemic metabolic abnormality and the abnormal systemic metabolism further decreases cardiac function, can be postulated. The hypothetical pathophysiology, nutrient axis, would deserve being tested, since the results would potentially improve the management of patients with heart failure. It would also be of interest, to examine the relationship between the nutrient axis and the other pathophysiological mechanisms. 157 シンポジウム Seiji TAKASHIMA Mitochondria are important organelle as a source of energy as well as oxidative stress. It has been believed that increased mitochondrial oxidative stress damages mitochondrial DNA （mtDNA）, which causes dysfunction of respiratory chain, and further mtROS production in cardiac remodeling. In fact, mtDNA decreased, and oxidative stress is increased in failing myocardium. We deﬁned the role of mtDNA copy number in cardiac remodeling using two kinds of molecule, mitochondrial transcriptional factor A（TFAM）and mitochondria NA helicase, Twinkle, both of which are known to regulate mtDNA copy number. Overexpression of TFAM in isolated myocytes reduces the immediate superoxide production from mitochondrial respiratory chain, and the subsequent redox sensitive signaling in nucleus such as MMP2, and MMP9. Moreover, the overexpression of either molecule in mice increased mtDNA about two times compared to wild type and attenuated eccentric hypertrophy accompanied by a suppression of MMP2 as well as MMP9 from the early stage of volume overload under the same level of antioxidants, respiratory enzymes, and hemodynamics. The level of reactive oxygen species（ROS）production decreased in myocardium from both transgenic mice, however, the level of oxidized mtDNA increased in those transgenic mice. We found an increase of mtDNA in myocardium will be protective from cardiac remodeling by reducing ROS. Targeting mtDNA may be a novel strategy for the treatment of HF. 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S12-5 Immunometabolic Cell Communication in Heart Failure Ichiro MANABE Department of Cardiovascular Medicine, The University of Tokyo, Tokyo, Japan Chronic inflammation underlies the development of various non-communicable diseases. Obesity induces active inflammation in visceral adipose tissue, which promotes inflammation in distant tissues. On the other hand, inflammatory processes lead to metabolic dysfunction at the tissue as well as systemic level. As such, immunity and metabolism appear to be inextricably linked and coordinated by common regulatory axes. Previously we demonstrated that cardiac ﬁbroblasts are essential for the adaptive response of the heart to pressure overload. Cardiac fibroblasts paracrine factors, including IGF-1, and induce hypertrophy in cardiomyocytes. In addition to fibroblasts, we found that pressure overload activates cardiac tissue macrophages, which are pivotally involved in the adaptive response in part by controlling metabolism within cardiomyocytes. Moreover, we found that kidneys aﬀect the cardiac macrophage activation and function. These ﬁndings suggest that the heart adaptively responds to pressure overload by intricate immunometabolic mechanisms that involve multiple tissues. シンポジウム 158 プログラム・抄録集シンポジウム１３（S13）心不全と呼吸管理 S13-1 S13-3 Beneﬁts and Risks of Oxygen Therapy in Acute Decompensated Heat Failure Unloading Eﬀect of Positive Airway Pressure Therapy Masamitsu SANUI、Hideyuki MOURI、Tadashi KAMIO Tsuyoshi SHINOZAKI、Takeshi ISHIDUKA、Noriko ONOUE、 Nobuhiro YAMAGUCHI、Hiroshi FUJITA Jichi Medical University Saitama Medical Center, Department of Anesthesiology and Critical Care Medicine For maintaining oxygen delivery to vital organs, oxygen is one of the most universal medications in various critically ill conditions including acute decompensated heart failure （ADHF）. However, its clinical benefits are not clearly documented in the literature. In most ADHF cases, oxygen is routinely administered as ﬁrst-line therapy, while potential harms of oxygen to the heart are often overlooked. Those potential deleterious eﬀects include reduction in heart rate, increase in systemic vascular resistance, impairment of cardiac relaxation and increased LV filling pressures [1,2]. In acute myocardial infarction, oxygen administration may constrict the coronary arteries, decrease oxygen delivery, and worsen myocardial ischemia [3]. Clinicians should balance the beneﬁts of oxygen therapy with its harms. In my part, a review of the clinical and experimental data on oxygen therapy in ADHF will be conducted. Also, as highﬂow nasal oxygen therapy, a newly introduced, easy-to-use modality of oxygen administration is gaining popularity, clinical data and our experiences of will be reviewed. References: 1. PMID 20350990, 2. PMID 11502645, 3. PMID 22017777 S13-2 Respiratory Care Using NPPV for Patients with ADHF: Principal Role of PEEP, CPAP, BiPAP and ASV 1） Cardiovascular Center, Nippon Medical School Chiba Hokusoh Hospital、2）Intensive Care Unit, Nippon Medical School Chiba Hokusoh Hospital、 3）Intensive Care Unit, Nippon Medical School Hospital、 4） Department of Cardiovascular Medicine, Nippon Medical School Patients with acute decompensated heart failure（ADHF）present with clinical features of orthopnea and hypoxic respiratory/ circulatory failure due to acute pulmonary edema. Emergent respiratory care to improve the tissue oxygenation and cardiovascular hemodynamics should be urgent. In the former endotracheal intubation era, we reported intermittent positive pressure breathing with optimal-level PEEP significantly decreased HR, PCWP, and PaCO2, and significantly increased PaO2, pH, and Stroke Work Index in patients with ADHF due to AMI（Jpn Heart J, 1986）. Induction of NPPV using nasal CPAP showed significant decrease in HR, mean PAP, PCWP, and acute phase emergent intubation rate and in-hospital mortality compared with the conventional care in patients with ADHF due to AMI（Jpn Circ J, 1998）. Over the two decades in our ICU, the rate of BiPAP use was increased from 22.7% to 66.5% in patients with ADHF, and total hospital stay was signiﬁcantly shortened following BiPAP Vision era. The retrospective analysis revealed that predictor of successful BiPAP Synchrony or BiPAP Vision application was pH7.20（AUC: 0.725）and pH7.03（AUC: 0.910）, respectively（J Cardiol 2010）. ASV use for ADHF and refractory CHF is also currently focused（SAVIOR-R and SAVIOR-C, 2014）. Principal roles of NPPV in ADHF management are reviewed. Background）Positive airway pressure（ PAP）therapy decreases preload, leading to a decrease in stroke volume based on Frank-Starling's low in healthy persons. Several reports, however, showed that PAP therapy increased stroke volume in patients with chronic heart failure （CHF）. These conflicting observations may be explained by diastolic ventricular interaction, which is a notion that the compliance of one ventricle inﬂuences that of the other under conditions of high pericardial pressure. Methods）To test this hypothesis, the immediate effect of PAP therapy （end-expiratory pressure 5±1 mmHg）to LV end-diastolic diameter（ LVDd）and velocity-time integral（VTI）in LV outflow were investigated in 5 patients with stable CHF . Sampling data （LVEF 37±19 %, NT-BNP 3814±2957 pg/ml） were averaged using 5 consecutive beats in patients with sinus rhythm and 10 consecutive beats in patients with atrial ﬁbrillation. Results） PAP therapy increased LVDd from （p<0.05）, and VTI from 17.8±2.7 58.3±8.5 mm to 60.9±9.9mm cm to 20.2±3.2 cm（p<0.01）, but did not change heart rate. Correlation coeﬃcient of percent change of VTI to percent change of LVDd was 0.79. Conclusions）Unloading effect of PAP therapy increased LV stroke volume in a manner dependent on LV volume. Diastolic ventricular interaction and Frank-Starling's low may underlie this observation. S13-4 Do Adaptive Servo-ventilation Improve Prognosis in Heart Failure Patients? Akiomi YOSHIHISA Department of Cardiology and Hematology, Advanced Cardiac Therapeutics, Fukushima Medical University, Fukushima, Japan Chronic heart failure（CHF）is a prevalent syndrome with poor prognosis, and is associated with co-morbidities such as arrhythmia, chronic kidney disease, anemia, and sleep-disordered breathing. Adaptive servo ventilation （ASV）is a ventilator support system specifically designed to normalize ventilation in CHF patients with or without SDB. ASV can regulate the airway ventilation according to the demand based on the variable tidal volume, improve pulmonary congestion, and increase cardiac output. We demonstrate that short and long term impacts of ASV on CHF patients from a view point of 1） ventricular arrhythmia, 2）chronic kidney disease, and 3）anemia. In summary, ASV decreased ventricular premature complex, and increased left ventricular ejection fraction and glomerular filtration rate. Furthermore, ASV improved long term prognosis in patients with CHF and CKD, and with CHF and anemia. Adaptive servo ventilation might be a promising useful tool for CHF as an important non-pharmacotherapy. 159 シンポジウム Yoshihiko SEINO1）、Akihiro SHIRAKABE2）、Noritake HATA2）、 Shinhiro TAKEDA3）、Wataru SHIMIZU4） Department of Cardiovascular Medicine, Sendai Medical Center, Sendai, Japan 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S13-5 Pulmonary Rehabilitation of Heart Failure Hiroko MIYAZAKI The Rehabilitation Medicine, Kyoto-Katsura Hospital, Kyoto, Japan As illustrated in Wasserman's cogwheel, there are close relations between blood circulatory system and respiration system. Pulmonary physical rehabilitations, such as changeof-position method and hand-assisted respiration etc., are useful for the patients of heart failure using respirator for respiratory insufficiency. Those rehabilitations develop clearing secretion, improving gas exchange and early leaving from respirator. And also those prevent the patients from the disorder of DLD caused by bed rest, i.e., are useful to prevent them from disuse syndrome. Aerobic exercise aiming AT and muscle training are recommended for the stable chronic heart failure patients and for the patients with chronic pulmonary disease such as COPD. In the patient with both chronic heart failure and COPD, the exercise prescription should be done safely considering the more critical disorder. For example, if the heart failure is the more serious, the rehabilitation prescription should be done aiming AT evaluated by CPX. But on the contrary, if the pulmonary disorder is the more critical, the patient is probably unable to aim at AT because of dyspnea and hypoxia. The rehabilitation should be performed as follows, medication of bronchiectatic drug beforehand or dosage of oxygen during exercise, assisting ventilation such as NPPV, observing dyspnea and SpO 2 as guideposts. Pulmonary rehabilitation prevent the patients of heart failure from and improve respiratory and cardiac disorder. シンポジウム 160 プログラム・抄録集シンポジウム１４（S14）急性心不全を予防するために S14-1 心不全の再入院を予防する！ -ハートチームの役割衣笠良治、杉原志伸、山田健作、加藤雅彦、山本一博鳥取大学医学部病態情報内科学人口の高齢化とともに心不全患者は年々急増している。心不全患者は生涯、何回も急性増悪をきたし、そのたびにれるような苦しみを味わう。繰り返す再入院を予防するにはどうすればよいであろうか？欧米では 20 年以上前から多職種チームによる包括的介入の有効性が報告されている。しかし、日本でのとりくみは大きく遅れており、日本の文化、医療システムにあったプログラムの作成が急務である。プログラムにかかせないのは標準的な医学的介入を十分におこなうことである。例えば、β遮断薬は収縮不全の患者に有効性が確立されているにもかかわらず、実地臨床では使用率、使用量ともに低いことが指摘されている。医師の知識不足、努力不足による再入院が少なからず存在することを認識しなければならない。更に、医学的介入の効果を最大限に発揮するためには、患者教育、リハビリー、福祉サービスの導入などメデイカルスタッフと協力した包括的な介入が不可欠である。当院では多職種介入を主体とした独自の心不全再入院予防プログラムを作成して診療にあたっている。本シンポジウムでは当院での取り組みについて紹介する。 S14-2 外来診療における急性心不全の予防∼心不全看護外来の果たす役割とアウトカム∼ 仲村直子【背景】慢性心不全患者の増加に伴い、急性増悪による再入院の予防が課題であり、外来診療は重要な役割を担っている。【目的】心不全看護外来開設から 3 年間の介入を急性心不全予防の視点で振り返り、心不全看護外来の果たす役割とアウトカムを明らかにする。【方法】対象：心不全入院歴があり、2 回以上心不全看護外来を受診した 42 名（男性 29 名、69.0%）。年齢、基礎疾患、左室駆出率（EF）、受診理由、内服薬、転帰、再入院の有無、入院経路などを単純統計で分析する。、心【結果】平均年齢 69.6±10.7 歳、虚血性心疾患 21 名（50.0%）筋症 10 名（23.8%）、弁膜症 3 名（7.1%）、高血圧性心疾患 3 名（7.1%）、その他 5 名（11.9%）であった。平均 EF36.3±16.3%、 EF20% 未満の患者が 8 名（19.0%）であった。心不全の再入院は 14 名（33.3%）、のべ 40 回に及び、3 年間に死亡した患者は 10 名（23.8%）であった。外来で内服調整された患者は 21 名（50.0%）であった。【考察】心不全看護外来では、心不全患者の体調を崩しやすい季節や活動を把握し、事前に対処できるが、それだけでは再入院を避けられない。今後は、再入院の経路や在院日数の短縮、在宅療養の連携などをアウトカムに看護外来を評価する必要がある。心不全患者の服薬アドヒアランス向上を目指して ∼薬剤師の立場から∼ 増田有紀広島大学病院薬剤部心筋塞二次予防ガイドラインで推奨される薬剤は、抗血小板薬、β遮断薬、ACE 阻害薬、ARB、脂質代謝異常改善薬等であり、適切な薬物療法の推進には、服薬アドヒアランスの向上が欠かせない。しかし、病識や服薬に対する認識不足から正しい服薬が出来ていないことを多々経験する。広島大学病院心不全センターでは、多職種カンファレンスや心不全教室などを開催し、患者への介入および教育を行っている。薬剤師は、患者への服薬指導やカンファレンスにて服薬アドヒアランスの評価および効果・副作用のモニタリング、薬物相互作用の確認、腎機能に応じた投与設計などの薬学的管理を行い、ファーマシューティカル・ケアの実践に取り組んでいる。現在は、心筋塞・心不全手帳を用いた地域連携パスを使用して、退院後も在宅においてその治療かつ予防に重点をおいた介入を行っている。心不全患者は、高齢化していることや合併症など多様な問題を抱えている場合が多く、問題解決には、多職種が専門性を発揮し連携をとることが不可欠であり、問題点とゴールの共有化が重要である。当日は、心不全センターにおける薬剤師の具体的な介入について紹介する。 S14-4 心不全症例における心エコー検査の役割勝木桂子大阪大学医学部附属病院超音波センター近年、慢性心不全症例における治療目的は再入院予防に重点が置かれている。ここに心エコー検査はどのように関わるべきであろうか？生活習慣や服薬指導、リハビリテーション、治療効果判定や増悪所見の有無を簡便にチェックする検査法として有用であり、ハートチームの中では「モニター的な役割」が求められていると考える。【心エコーで評価する項目】・心不全を来した原疾患（弁膜症など）の増悪はないか・心室壁運動（左室駆出率）・心房、心室の大きさ・左室拡張末期圧の推定・心不全増悪を助長する二次性弁逆流の程度・下大静脈径（中心静脈圧のおおまかな推定）・心拍出量の推定・肺動脈圧の推定特に重症心不全例では上記項目のわずかな変化でも緩やかな増悪の始まりを示す一方で、単なる技術的エラーである可能性もある。これらを的確に判断し、再現性のある正確なデータを報告するのが心エコー技師の義務である。即ち、ハートチームの中で「患者に働きかける」ことがない異質な存在である我々技師はデータを出すだけで満足せず、わずかな所見の変化でも積極的にチーム内にフィードバックし、患者の治療状況や他検査の結果を把握する必要がある。 161 シンポジウム神戸市立医療センター中央市民病院看護部 S14-3 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S14-5 心不全患者の予後因子としてのADL 当院心不全チームの取り組みと理学療法士の役割齋藤洋亀田総合病院リハビリテーション室本邦の高齢化率（65 歳以上人口が総人口に占める割合）は、今後一貫して増加することが予測されている。慢性心不全に対する運動療法介入は心不全の増悪を予防したという報告はあるが、その一方で高齢者に対する運動療法の効果は限定的であることも報告されている。急性心不全に対する運動療法の効果は示されていないが、急性心不全症例に対する疾病管理を含む包括的な心臓リハビリテーション介入は予後を改善する可能性がある事が示されている。当院では多職種心不全チームにて急性心不全症例に対する包括的な介入を実施しているが、その中で理学療法士は、特に廃用症候群を予防する目的に入院早期より段階的に ADL 練習を開始している。これまで高齢心不全患者における ADL の予後との関わりは報告が少ないが、当院では理学療法士が認知機能を含む ADL を心不全増悪における重要な予後因子として認識し、検討してきた。ADL の何が心不全患者の予後に影響しているのか、また入院中の ADL を高く保つ介入が予後を改善する可能性があるのかを含め、本シンポジウムでは理学療法士による ADL 練習や疾病管理について検討したい。 S14-6 国立循環器病研究センターにおける食事業の展開 ∼かるしおレシピの均てん化∼ シンポジウム村井一人、上ノ町かおり、佐藤友紀、北川冬華、竹田博幸、時田和敏、糸林俊夫、中谷武嗣国立循環器病研究センター臨床栄養部栄養管理室 [ 背景 ] 心不全患者において食事療法は重要である。入院中は提供された病院食を喫食せざるを得ず食事療法は遵守されやすいが、病院食は栄養管理、材料単価、労働力、衛生管理など守るべき要素が多く、嗜好面では不評になりがちである。そして退院後は、嗜好に任せた食事になったり、自己での炊事が困難なため食事療法が遵守できないことが多い。[ 目的 ] 食事療法は、循環器疾患の進展予防のため重要であり、病院食はその教材になる物と考える。我々はできるだけ美味しい食事が提供できるよう病院食の改革に取り組んだ。[ 展開 ] その結果「懐石料理を食べているようだ。」「家での食事よりずっと美味しい。」との声が多く寄せられるようになった。さらに " 入院以外でもこの食事を提供してほしい。" との声が医師、患者などより強く寄せられ、料理教室や国循食の料理を活かした弁当の販売や、企業の社員食などに提供するなど、広く事業展開した。また、出版した「国循の美味しい！かるしおレシピ」は続編を合わせ 33 万部発行した。その他、循環器疾患の制圧に食方面から介入するため全国的な食事コンテスト（S-1g）も開催した。今後、これら事業による結果を検証したい。 162 プログラム・抄録集シンポジウム１５（S15）慢性心不全 S15-1 S15-3 心不全患者の退院支援における慢性心不全認定看護師の役割慢性心不全患者に対する退院支援ファイルの活用とカンファレンスの実際壽慶奈津子岡田悦代地方独立行政法人りんくう総合医療センター国立循環器病研究センター看護部近年心不全患者は増加傾向であり、患者が抱える問題として生活習慣の改善困難、独居や高齢者世帯など社会的問題から治療で病状が軽快しても、退院後心不全が再燃する現状がある。そのため、患者の QOL 向上を考え心不全患者特有の退院支援を実践する必要があると考えた。入院時スクリーニングを行い、退院後心不全管理が難渋すると予想される患者に問題解決思考で看護介入を行った。その結果、A 氏は心筋塞を発症後、セルフモニタリング行動を獲得し、心負荷を軽減するよう社会資源を活用し高齢母親の介護という役割遂行ができた。B 氏は重症心不全で2年間転院を繰り返していたが、家族とテーブルで食事ができるよう活動耐性を高めた。ストレスフルの家族はレスパイトケアを受け入れ、役割緊張のリスクを回避できた。30 歳代の C 氏は生活習慣病から心不全を呈した。得意な家事を積極的に行うことで自己効力感を高め、生活習慣を改善した。今回の看護介入から、心不全患者の退院支援における慢性心不全認定看護師の役割を、多職種で患者の活動耐性を高め退院に向けてマネジメントする、再入院因子を分析し社会資源を活用する、適切な情報提供を行うことと見出した。心不全患者の多くは入院中に医療者から受けた教育内容を実際の生活に組み込むことが容易ではない。その理由の 1 つとして患者のこれまでの生活背景や価値観などの情報収集の不十分さから個々の状態に応じた退院支援に至っていないことが挙げられる。私達看護師は心不全患者が病とどのように向き合い人生を歩んでいきたいのか、患者の意思を支援する役割を担っている。当病棟では心不全患者への退院支援に力を入れているが、心疾患を抱えた患者が社会資源を有効に活用することができないまま退院するケースも少なくない。そこで今回、患者の住宅環境や社会資源の利用など社会背景に焦点をあてた退院支援ファイルを作成した。看護師が患者をとりまく環境について重点的に情報を収集する習慣をもつことで、受け持ち患者へのプライマリー意識を高めるだけではなく、患者自身やサポートをする家族が入院中から早期に退院後の生活について考える機会をつくることができた。本シンポジウムでは、慢性心不全 stageC ∼ D 期にある拡張型心筋症を基礎疾患にもつ慢性心不全患者の退院支援の実際について報告し、退院支援に必要な看護の視点および具体的方法について皆様とともに考えたい。 S15-2 S15-4 療養者の生活安寧に関する訪問看護学的考察 ∼慢性心不全を抱える高齢者をいかに支えるか∼ 中麻規子村田直子広島大学病院心不全センター兵庫県看護協会資格認定教育部当院心不全センターは心不全患者の再入院率低下、QOL 改善のため、多職種協働で包括的心臓リハビリテーションや疾病管理を実践し、在宅療養や社会復帰を目指し、地域連携体制づくりに取り組んでいる。心不全センター専従看護師は院内で横断的に活動し、医師や病棟看護師、理学療法士など院内の多職種の他、地域の介護支援専門員などから相談を受けている。依頼は困難事例への対応などがあり、面接を行って倫理調整、家族支援、行動変容カウンセリング、退院後のテレナーシングなどを実践している。また、全診療科から依頼を受付けている心不全多職種チームへのコンサルテーションでは、カンファレンスの運営や職種間調整などを行っている。 2013 年度のカンファレンス対象者は 79 件であり、各々が持ち寄った情報を統合、ケアの方向性を検討し、在宅生活を視野に入れたサービスのコーディネーションや多職種間の調整（社会資源の導入、退院調整、病状説明支援、至適運動量の評価、自己管理支援など）を行っている。退院後は患者の生活状況を診療録や対面で確認し、必要に応じてフィードバック、サービスの再調整を行い、在宅で療養生活が送れるよう支援する役割を担っている。慢性心不全療養者は、心不全の増悪による再入院を繰り返すことが多い。慢性心不全治療ガイドライン（2005）によると、高齢心不全患者の予後改善には、多職種による退院前患者教育の強化、退院後の社会資源の積極的活用、訪問看護や電話によるフォローアップが有効であると言われている。訪問看護の役割は、疾病管理を生活の中に取り入れ、療養者と家族の希望する生活を支えることである。限られた訪問時間の中で、療養者の病状や生活状況のアセスメント、入浴介助やリハビリを行いながら、生活を調整している。主治医の意見や退院時共同指導で得た情報は、訪問看護師が行う病態アセスメントの質を向上させ、より良い在宅療養生活を療養者や家族に提案できると考える。今回、急性増悪入院の後、退院した 2 事例を紹介する。1 例目は、突然死の可能性を告知されたが、訪問診療と訪問看護を利用し、現在も在宅療養を継続している 80 歳代の男性である。一方、2 例目は退院後も病状が安定せず、1 ヶ月後の外来受診の際に病院の廊下で死亡した 90 歳代の女性である。これらの事例を訪問看護の視座から省察し、病院と在宅が 1 つのチームになるための情報共有について議論したい。 163 シンポジウム慢性心不全患者の在宅療養支援・地域連携推進に向けた心不全センター看護師の役割第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S15-5 重症慢性心不全患者に対する在宅ASV療法と心房細動合併心不全患者に対するアブレーション治療選択の意義竹内素志 1）、武居明日美 2）、吉田明弘 3） 1）医療法人社団竹内内科、2）神戸労災病院循環器内科、3）神戸大学大学院医学研究科循環器内科学分野不整脈先端治療学部門高齢化社会にあって慢性心不全患者のさらなる増加が予想され標準的薬物治療に加わる新たな治療法が望まれている。慢性心不全患者に対し在宅治療可能な陽圧換気療法（CPAP/ ASV）をクリニックにて導入、また心房細動合併心不全患者に対して連携病院にてアブレーション手術を施行し心機能改善効果を検討した。対象は当院通院中の症候性慢性心不全患者 107 例（男性 63 例、女性 44 例、平均 75 歳、NTproBNP>900pg/mL）。基礎疾患の内訳は高血圧 56 例、虚血性心疾患 21 例、心筋症 16 例、弁膜疾患 14 例であった。対象患者 107 例中 70 例（65%）に心房細動の合併を認めた。NTproBNP 値、心エコー左室内径短縮率 : %FS の推移を観察した。標準的薬物治療に加えて睡眠呼吸障害合併心不全患者 8 例に CPAP 治療、重症心不全患者 6 例に ASV 治療を施行した。また心房細動合併心不全患者15例に連携病院にてアブレーション手術を施行し入退院前後で評価した。CPAP 治療追加群では NT-proBNP 値が低下したが %FS に変化を認めなかった。一方 ASV 治療追加群、アブレーション手術群では NTproBNP と %FS の両指標に有意な改善を認めた。以上から慢性心不全治療追加オプションとしての在宅 ASV 療法、並びに心房細動合併心不全患者に対するアブレーション治療選択の有用性が示唆された。シンポジウム 164 プログラム・抄録集シンポジウム１６（S16）心不全における心房細動の治療の意義 S16-1 S16-3 Management of Atrial Fibrillation in Heart Failure: Overview Catheter Ablation of Atrial Fibrillation with Concomitant Heart Failure Shinsuke MIYAZAKI Koichiro KUMAGAI Cardiovascular center, Tsuchiura Kyodo Hospital Heart Rhythm Center, Fukuoka Sanno Hospital, Fukuoka, Japan Chronic heart failure and atrial fibrillation are 2 major disorders that are closely linked. Their coexistence is associated with adverse prognosis. As both share common risk factors, their pathophysiology is highly interrelated and a lot of patients present with both conditions. Anticoagulation and rate control are important. Control of heart rate is always prudent though still not precisely defined. Elderly patients derive the most benefit from anticoagulation, but are also more prone to bleeding complications. Routine use of antiarrhythmic drug therapy for maintenance of sinus rhythm carries concerns of risk and limited eﬃcacy. Catheter ablation for maintaining sinus rhythm is feasible for some patients, but further studies are needed to deﬁne the risks and beneﬁts. A role remains for AV junction ablation and pacing, with consideration of biventricular pacing to prevent dyssynchrony induced by chronic right ventricular pacing. Further progress toward improved understanding the complex relationship between atrial ﬁbrillation and heart failure should improve management strategies. Catheter ablation for the treatment of atrial ﬁbrillation （AF） is currently recommended by guidelines as a second-line therapy in patients with paroxysmal and persistent AF after treatment with at least one antiarrhythmic drug has failed and, under special circumstances, can be oﬀered as ﬁrst-line therapy. The randomized trials support the statement in the guidelines that catheter ablation of AF is more eﬀective than antiarrhythmic drug therapy in maintaining sinus rhythm. AF with concomitant heart failure remains a challenging combination when rhythm control therapy is needed. The recommendations for antiarrhythmic drug therapy leave amiodarone as the only available antiarrhythmic drug in this setting. Many patients are rendered asymptomatic or mildly symptomatic by amiodarone therapy, especially when heart failure and heart rate are well controlled. In patients who suffer from symptomatic AF recurrences on amiodarone therapy, catheter ablation remains as the sole choice for reliable rhythm control therapy. The main principles of rhythm control therapy apply to this group of patients as well, speciﬁcally that rhythm control therapy is indicated to improve AF-related symptoms. The likelihood of maintaining sinus rhythm after catheter ablation is lower and the procedure-related risks may be higher in heart failure patients. In selected patients suﬀering from heart failure and treated in highly experienced centers, catheter ablation of AF may provide an improvement in left ventricular function. S16-2 Management of Patients with Heart Failure and Atrial Fibrillation; is Catheter Ablation a Hoping Star? Cardiocascular Center, Sakurabashi Watanabe Hospital Atrial fibrillation（AF）and heart failure（HF）often coexist in the same patients. AF drives HF, and HF also drives AF. So interruption of this vicious cycle is very important. However, because maintenance of sinus rhythm by antiarrhythmic drugs（ AADs）is difficult very frequently, and AAD have risk of advertise events, such as lethal arrhythmia and HF, the prognosis of rhythm control strategy using AAD was not superior to that of rate control strategy. Catheter ablation for AF was the most effective strategy to maintain sinus rhythm today. The previous studies consistently reported that AF ablation improved left ventricular ejection fraction（LVEF）in AF patients with HF. Meta-analysis of previous 8 trials revealed that LVEF improved in 10.9%（95% conﬁdent interval; 7.3-14.3%）by AF ablation in HF patients. Recently, two clinical trials were reported, in the both of which persistent AF patients with HF were randomized to AF ablation group and medical treatment group. These trials consistently revealed that AF ablation can improve LV function, functional capacity, and HF symptoms compared with rate control. CASTLE-AF, RAFT-AF trials, and AMICA trial, which address the role of catheter ablation versus medical therapy for management of AF in substantially larger numbers of HF patients than current study, were on-going now, and their outcome will be reported soon. Pharmacological Treatment of Atrial Fibrillation in Patients with Heart Failure Tsuyoshi SHIGA Department of Cardiology, Tokyo Women's Medical University, Tokyo, Japan Atrial fibrillation（AF）frequently occurs in patients with heart failure. It is recognized that AF leads to clinical deterioration and results in worsening heart failure. AF also increases the risk of mortality and morbidity in patients with heart failure. ESC guideline 2010 introduces treatment recommendations for the management of AF in patients with heart failure. 1）Background heart failure treatment should be optimized, 2）Oral anticoagulant is generally Ventricular rate control is indicated when AF is present, 3） required. Beta-blockers are preferred over digitalis and have favorable eﬀects on mortality and morbidity in patients with systolic heart failure. 4） The rhythm control strategy has not been shown to be superior to rate control in heart failure patients with AF（AF-CHF trial）. However, restoration of sinus rhythm may improve symptoms and hemodynamics in heart failure patients with AF. Amiodarone can be safely used in patients with heart failure. In patients with AF and severe and unstable heart failure, intravenous amiodarone should be used to maintain sinus rhythm. The goal of pharmacological management is to improve in survival and quality of life in heart failure patients with AF. 165 シンポジウム Koichi INOUE S16-4 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S16-5 Clinical Impact of Cardiac Resynchronization Therapy in Patients with Atrial Fibrillation Takashi NODA1）、Kengo KUSANO1）、Ikutaro NAKAJIMA1）、 Toshihisa ANZAI1）、Masaharu ISHIHARA1）、Satoshi YASUDA1）、 Masafumi KITAKAZE1）、Hisao OGAWA1,2） Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan、2）Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan 1） Cardiac resynchronization therapy（CRT）is an effective therapy for patients with systolic dysfunction and a ventricular conduction delay. However, observational study and sub-analysis of a randomized clinical trial suggest that the beneﬁts of CRT are reduced among patients with atrial ﬁbrillation（AF）. We divided consecutive 133 CRT patients into two group; 35（ 26%）CRT patients with AF and 98 （74%）CRT patients with SR and the baseline characteristics were similar in both groups, except for gender distribution of male. The follow-up data revealed that the incidence of lethal arrhythmic events including ventricular tachycardia, ventricular fibrillation and sudden cardiac death was signiﬁcantly higher in the CRT patients with AF compared to the CRT patients with SR （Figure） . CRT patients with AF could be at a high risk for lethal arrhythmic events. シンポジウム 166 プログラム・抄録集シンポジウム１７（S17）HFpEF - 基礎研究から S17-1 S17-3 Pathophysiolgy of Heart Failure with Preserved Ejection Fraction; Evidence Based Medicine Medicine and Novel Approach Heart Failure with Preserved Ejection Fraction is Strikingly Exaggerated by Dysfunction of Autonomic Nervous System Takayuki HIDAKA、Yasuki KIHARA、Hideya YAMAMOTO、 Yukiko NAKANO、Satoru KURISU、Yoshihiro DOHI、 Toshirou KITAGAWA、Ken ISHIBASHI、Tatsuya MARUHASHI Takuya KISHI Hiroshima University Graduate School of Biomedical Sciences and Health Heart failure is closely associated with dysfunction of autonomic nervous system, such as sympathoexcitation and/or parasympathetic withdraw. Although β-blockers has established benefits on heart failure with reduced ejection fraction, heart failure with preserved ejection fraction（HFpEF）would not have consistent benefits of β -blockers. HFpEF are supersensitive to volume overload, and stressed blood volume are mainly controlled by baroreflex system. Major risk factors of HFpEF also promote atherosclerosis and thereby baroreﬂex failure. Therefore, we hypothesized that baroreﬂex failure plays a pivotal role in the pathogenesis of HFpEF independent of left ventricular dysfunction. We mimicked normal baroreflex by matching carotid sinus pressure（ CSP）controlled by a servocontrolled piston pump to instantaneous atrial pressure（AP）, and baroreflex failure（FAIL）by maintaining CSP at a constant value regardless of AP in normal rats. In FAIL, critical（left atrial pressure reached 20mmHg）infused volume（Vi）strikingly decreased, while AP at the critical Vi increased. In addition, we determined that bionic baroreﬂex system was able to fully reverse the volume intolerance in the FAIL. Recently, we showed that afferent vagal nerve stimulation（AVNS）resets the baroreflex neural arc and induces sympathoinhibition, suggesting that AVNS could in part attribute to the beneﬁcial impacts on HFpEF. In conclusion, we consider that dysfunction of autonomic nervous system, such as baroreﬂex failure, exaggerates HFpEF via induction of striking volume intolerance. The problems associated with heart failure with preserved ejection fraction（HFPEF）is increasingly important due to the transition to an aging society. However, we are faced with the fact that there is no consensus based on scientific evidence for the treatment and methods to improve prognosis and reduce medical cost in the high-risk population and patients with HFPEF. Nowadays, while left ventricular hypertrophy and diastolic dysfunction remain to be as central dogma in pathophysiology of HFPEF, the accumulation of several evidence has revealed that the mechanisms of HFPEF is highly complex and that cardiac dysfunction other than diastolic abnormality and extra cardiac factors such as increased arterial stiﬀness, abnormal ventricular-arterial coupling, endothelial dysfunction and abnormal response to exercise also contribute to the onset and progression of this syndrome. Here, we will discuss what is known and unknown about pathophysiology of HFPEF and explore a novel approach to the unresolved problems. S17-2 Involvements of Inﬂammatory Mediators in the Pathophysiology of Chronic Heart Failure with Preserved Ejection Fraction Cardiovascular Division, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan、2）Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan 1） Specific therapeutic strategies for chronic heart failure with preserved left ventricular（LV）ejection fraction（HFpEF）have not been established. Although inﬂammation contributes to cardiac remodeling such as cardiac ﬁbrosis in heart failure, inﬂammatory mechanisms and mediators involving in the development of HFpEF remain unclear. From screening of serum samples in HFPEF patients, several cytokines and chemokines（IL-16, CXCL9, stem cell factor, Eotaxin, and IP-10）were found to be candidates involved in HFpEF.Among them, serum interleukin-16 （IL-16）levels showed speciﬁc elevation in patients with HFpEF and was correlated with E/e, left atrial volume index（LAVI）, and diastolic wall strain（DWS）. Serum IL-16 levels were also elevated in a rat model of HFpEF and positively correlated with LV end-diastolic pressure, lung weight and LV myocardial stiffness constant. Enhanced cardiac expression of IL-16 in mice induced an increase in cardiac ﬁbrosis and LV myocardial stiﬀness, accompanied by increased macrophage inﬁltration into LV. Treatment with anti-IL-16 neutralizing antibody ameliorated cardiac fibrosis in the mouse model of angiotensin II -induced hypertension without affecting systemic blood pressure. Our data indicate that IL-16 is a mediator involved in LV myocardial ﬁbrosis and stiﬀening in HFpEF, and that the blockade of IL-16 could be a possible therapeutic option to treat HFpEF. S17-4 Impact of Adaptive Servo-Ventilation on Cardiovascular Function and Prognosis in Patients with HFpEF and Sleep-Disordered Breathing Akiomi YOSHIHISA、Satoshi SUZUKI、Yasuchika TAKEISHI Department of Cardiology and Hematology, Advanced Cardiac Therapeutics, Fukushima Medical University, Fukushima, Japan Eﬀective pharmacotherapy for HFpEF is still unclear. Sleep-disordered breathing（SDB）causes cardiovascular dysfunction causing factors of HFpEF. However, it remains unclear whether adaptive servoventilation（ASV）improves cardiovascular function and prognosis of patients with HFpEF and SDB. Thirty-six patients with HFpEF and moderate-severe SDB（LVEF 56.0%, apnea hypopnea index 36.5/ h）were assigned to two groups: 18 patients treated with medications and ASV（ASV group）and 18 patients treated without ASV（NonASV group）. NYHA class, Cardiac function including LVEF, left atrial volume index（LAVI）, E/E', vascular function including flow mediated dilatation（FMD）and cardio-ankle vascular index（CAVI）, and levels of BNP were determined before and 6 months later. Patients were followed to register cardiac events after enrollment （follow-up 543 days）.ASV therapy improved cardiac diastolic function and decreased CAVI and BNP（NYHA class: 2.3 to 1.5, LAVI: 48.6 to 42.6 ml/m2, E/E': 12.8 to 7.1, CAVI: 9.0 to 7.7, BNP: 121.5 to 58.1 pg/ml, P<0.0125, respectively）. LVEF and FMD did not signiﬁcantly change in either group. Importantly, the event-free rate was significantly higher in the ASV group than in the Non-ASV group（94.4% vs. 61.1%, log-rank P<0.05）. ASV may improve prognosis of HFpEF patients with SDB with favorable eﬀects such as improvement of symptom, cardiac diastolic function and arterial stiﬀness. ASV may be a useful therapeutic tool for HFpEF patients with SDB. 167 シンポジウム Toshiaki MANO1）、Shunsuke TAMAKI2）、Yasushi SAKATA2）、 Tohru MASUYAMA1） Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society シンポジウム１８（S18）日本における大規模研究の進め方 S18-1 Controversial Points and Future Direction of Clinical Trials in Japan Nobuyuki SHIBA International University of Health and Welfare Hospital Large clinical trials are essential to develop evidence-based clinical guidelines, which help physicians to improve the prognosis of patients. An investigator-initiated clinical trial （IIT）is the most popular style of clinical trials in Japan. The primary aim of IIT is academic rather than commercial purpose and the objectives of studies are not usually explored in sponsored trials. However, there are several problem points in performing IITs. First, the successful commencement, procession, and completion need many challenges such as; 1）the cooperation of a multidisciplinary research team, 2）knowledge and experience in the concepts and details of clinical trials, and ethical / legal adequate ﬁnancial resources for conducting considerations, 3） the trial. Second, surrogate markers may be adopted to predict a clinical outcome because of the cost and time constraints. Finally, extrinsic / intrinsic motivators must be considered to increase participants. Future research may be conducted more properly based on the following improvements; 1）Promotion of education about the clinical trials for medical stuﬀ and students, 2）To perform clinical trials under systematic management, 3）Open / aboveboard funding, 4）Promotion of developing clinical "big data" in the wide area, which will help the commencement of large epidemiological / observational studies, 5）The effective / appropriate utilization of information technology such as cloud-based electronic health record system. S18-2 Academic Trials: For What and How They Should be Done Shinichiro UEDA シンポジウム University of Ryukyus The most important issue in conducting any clinical research is to have clear purpose i.e. sensible clinical questions from clinical practice. Study design should be determined by the purpose of study but not by a hierarchical "pyramid of evidence". There are roughly two types of clinical research. Seeds driven research examines efficacy of new drugs for the approval by regulatory agencies and needs driven research is intended to resolve clinical questions. The former needs very strict study design i.e. double blind, randomised controlled trials with restrictive criteria for eligible patients and end-points under the strict regulation and guidance（ICH-GCP）with a few exceptions. Observational study design may fit the later but RCTs also are applicable as pragmatic trials in less restrictive design. Pragmatic RCTs may also ﬁt comparison of strategies of care. For example, intensive control of cardiovascular risk factors such as blood pressure is better to be compared to standard control by a RCT rather than a cohort study. However, unlike pharmaceutical trials, researchers in academic trials are haunted by concern about cost, enrollment of patients and quality control. Appropriately constructed registries of patients may help researchers overcome such obstacles. Prospective or even retrospective collection of welldeﬁned outcomes and variables may allow researchers to conduct clinical trials let alone sensible cohort studies, case-control studies and cross-sectional studies based on one registry. Proper data management and central statistical monitoring of registries by biostatistician may improve quality of data at lower cost. 168 S18-3 Clinical Study Design and Data Analysis Satoshi MORITA Department of Biomedical Statistics and Bioinformatics, Kyoto University Graduate School of Medicine, Kyoto, Japan Basic statistical knowledge may be required to understand statistical methods. What clinical investigators need, however, is to appropriately interpret data / results observed in clinical trials, not statistical knowledge. This lecture will provide fundamental and useful statistical "skills" to design clinical trials and analyze data from them. S18-4 How to Organize Clinical Research Support System in an Institution on the Conduct of Large Studies Shuichi KAWARASAKI The University of Tokyo Hospital Managing clinical research in high evidence level requires randomized large sample size and collaboration with multi institutions. However, as the size of a clinical study becomes large, conduct of such a study becomes more complicated, and involvement of specialists knowledge are highly required. In Japan, where clinical studies are frequently without abundant budget, it is diﬃcult to outsource works required to conduct a study. In addition, it will be expected to perform monitoring and audit under the upcoming guideline for clinical research. Under those circumstances, it is essential to set up a well-organized clinical research support within the institution with robust support from each specialists with the knowledge in biostatistics, data management, monitoring and audit. By showing the result from analysis of around 300 clinical studies which were applied for IRB in past ﬁve years in our hospital, discussion on the new clinical research support system at an institution under the new guideline will be addressed. プログラム・抄録集シンポジウム１９（S19）重症心不全治療の現状と今後 S19-1 S19-3 重症心不全治療の現状と今後内科の立場から 1） 1） 2） 2）肥後太基、井手友美、田ノ上禎久、富永隆治、砂川賢二 1）九州大学病院循環器内科、2）九州大学病院心臓血管外科 1）最近の植込型左室補助人工心臓（VAD）の保険償還をうけ、重症心不全の治療として将来の心臓移植手術を前提とした VAD 植込み術が普及しつつある。それに伴い心臓移植までの数年にもおよぶ長期の待機期間中の管理体制構築が重要になりつつある。当院では、ハートセンターという単一の診療ユニットで内科と外科が連携して患者管理に関わり、退院後も両者が共同で診療を行う体制を整えた。同時に多職種から構成される VAD カンファレンスを通じて、VAD の設定のみならず創部の管理や日常生活指導、栄養サポートや運動療法、精神状態の評価など、ハートチームとして包括的な管理を行うことで、患者が安心して長期の移植待機期に臨めるよう努めている。重症心不全治療においていまや LVAD や心臓移植といった治療はもはや珍しい治療ではなくなりつつあり、内科医といえども、いや内科医こそが補助人工心臓治療や心臓移植治療に十分精通したうえで、適切な患者選択、多職種と連携した長期の移植待機、移植後管理に努めていく必要があると考えられる。 S19-2 東北大学病院における重症心不全患者の治療選択の現状秋葉美紀東北大学病院臓器移植医療部／看護部本邦では植込み型補助人工心臓は心臓移植待機患者にのみ使用することができ、その心臓移植登録の適応年齢は 65 歳未満まで拡大された。当院でも心臓移植と植込み型補助人工心臓装着の適応となる重症心不全患者の紹介は増加している。植込み型補助人工心臓装着患者は、在宅治療が可能であり、さらに、条件がえば社会復帰も可能である。2014 年 8 月現在で植込み型補助人工心臓装着患者は 16 名で、そのうち 12 名が在宅治療へ移行しており、6 名は社会復帰している。しかし、植込み型補助人工心臓装着には様々な条件があり、患者が重要視するのは「24 時間 care giver の存在」と「自動車運転の禁止」である。東北地方は公共交通機関が限られているため「自動車の運転ができない＝日常生活を送れない」と考える患者が多い。また、高齢の二人暮らし世帯が多いのも特徴に挙げられる。さらに、心臓移植には多額の臓器搬送費用負担が求められる。このような様々な事情を考慮し、心臓移植医療を躊躇する患者もいるのが現状である。患者、家族の治療選択時には、的確な情報を提供し、意思決定支援を行うことが重要である。 S19-4 心臓移植後患者に対するレシピエント移植コーディネーターの役割大岡智学 1）、新宮康栄 1）、若狭哲 1）、橘剛 1）、松居喜郎 1）、原守 2）、絹川真太郎 2）、山田聡 2）、筒井裕之 2）、小林真梨子 3）久保田香北海道大学大学院医学研究科循環器呼吸器外科、2）北海道大学大学院医学研究科循環病態内科学、3）北海道大学病院臓器移植医療部移植後患者は、VAD から解放されるが、新たに免疫抑制療法や厳重な感染管理、食事管理などを要す。移植後の合併症や免疫抑制剤による副作用の予防が長期予後を左右するが、それらの合併症は患者の自己管理で回避できるものも多い。レシピエント移植コーディネーター（RTC）は、心臓移植後も長期継続したケアを行っている。RTC は退院指導パンフレットを作成し、それをもとに病棟看護師が指導を行う。RTC はそれを評価し退院後の継続ケアにつなげている。退院後は、自己管理表による評価などの日常生活指導を行い、必要時には栄養士による栄養指導の依頼や調整、精神的ストレスに対しては、臨床心理士の介入依頼を行っている。また体調不良時の相談窓口となり、合併症発症時の専門医への受診手配や、体調不良時の初期対応や継続加療を近医へ依頼する。さらに社会復帰支援として患者との仕事内容の相談のみならず、 VAD 装着中の脳合併症により麻痺の残存など移植後の社会復帰に影響を及ぼしている場合もあり、職場への情報提供を行う。このように移植後患者は、包括的なチーム医療を継続する必要がある。そのため RTC は多職種との連絡・調整の中心的役割を担っている。 1）【背景】当施設は、改正臓器移植法施行に併せ、新規認定された心移植実施施設である。院内体制構築から約 4 年が経過し、植込型補助人工心臓（VAD）治療を経て、心臓移植実施に至った。【ハートチーム構築の過程】数名の working group から始まった体制構築は、総勢 40 名弱の multidisciplinary team となり、定期カンファレンス（週 1 回）を開催している。啓発・意識向上を目的とした院内勉強会、院外啓発活動とした教育的講演を市内・市外で開催した。移植実施へ向け、計 3 回院内シミュレーションを実施し心臓移植実施マニュアルの brush up を行った。【移植適応患者の現状】2010 年 7 月以降 15 名の移植適応申請を行った。現時点での待機患者は 10 名（うち 1 名は施設変更）。植込型 VAD 装着下の待機患者は 6 名（4 名が在宅待機）、内 1 名は事後検証申請。植込型 VAD 装着後死亡・右心補助追加例はないが、体外式 VAD1 名を失った。心移植 2 例を実施し、外来管理を行っている。【展望と課題】本邦の移植待機は、待機期間の延長により欧米における永久使用と同等となる。ハートチームとして、時機を逸しない適応検討及び申請と抗凝固療法・感染・右心不全に対する質の高い長期管理が要求される。大阪大学医学部附属病院移植医療部 169 シンポジウム北海道大学における重症心不全治療の現状と今後 −ハートチーム構築から心移植へ− 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S19-5 補助人工心臓と共に生活する患者を支えるということ山中源治東京女子医科大学病院看護部内科的治療の限界にある末期の重症心不全患者には、心臓移植が必要である。しかし、日本での心臓移植待機期間は平均 1000 日近い状況にあり、ほとんどの心臓移植待機患者は補助人工心臓を装着している。 2011 年に保険償還された植込型補助人工心臓は、耐久性の向上やコントローラ・バッテリーの小型化により、退院することが可能となり、QOL の向上が期待されている。一方で、さまざまな合併症の問題も残されており、最悪の状況では、生命が危機的状況に陥ることもある。合併症予防には、患者・家族を含めたチーム全体で取り組む必要がある。さらに、精神的なケアを必要とする患者も少なくない。医学的に問題がない患者であっても、過去や他者と比較し、生活や人生に不満や不安を抱える者もいる。VAD と共に生活する患者を支えるためには、その患者の人生行路を理解しようと努めることからケアは始まる。 S19-6 重症心不全治療の現状と今後（臨床工学技士の立場から）久保仁シンポジウム東京大学医学部附属病院医療機器管理部重症心不全に対する治療は、内科と外科それぞれの治療法の進歩や技術の向上により効果的な治療が可能になった。一方で、治療抵抗性の重症心不全では、補助人工心臓の装着を行い、心臓移植へ移行していく症例も多くなっている。植込み型補助人工心臓を装着した患者は、一部制限はあるものの自宅療養や社会復帰が可能となる。自宅療養に移行するためには患者と介護者に補助人工心臓についてのトレーニングを実施するが、介護者が高齢である場合も多く、教育法や習得度の判断が難しいケースも多くなっている。また、自宅療養に移行した後のトラブルも少なくなく、様々なトラブルの状況を見極め対応するには、外来受診時の機器 check だけでは難しく、当院では定期的に在宅患者と web カメラを用いて情報交換を行う取り組みを実施している。ここでの情報を医療チームの中で共有する事で、在宅中に発生した問題への対処が迅速に行える様になった。この一連の治療は、入院から移植に至るまで様々な医療職種と患者がチームとして連携する事ではじめて成立する治療であると考える。当院での重症心不全治療への取り組みと今後の課題について臨床工学技士の立場から考えてみたい。 170 S19-7 補助人工心臓装着患者および心臓移植後患者の QOLと社会復帰堀由美子 1）、伊藤文代 2）、中谷武嗣 3） 1）国立循環器病研究センター看護部移植部、2）国立循環器病研究センター看護部、3）国立循環器病研究センター移植部【はじめに】院内待機を要する体外設置型補助人工心臓（体外設置型 VAD）から在宅管理が可能な非拍動流型植込型補助人工心臓（植込型 VAD）が保険償還され、待機患者の QOL の向上が期待された。今回、VAD 装着患者と心臓移植後患者の QOL と社会復帰の現状を調査したので報告する。【方法】対象：1）VAD 患者 43 名（体外設置型 5 例、植込型 38 例）。平均補助期間 518±304.1 日 2 移植後患者 58 名。平均移植後年数 5.4± 4.2 年。調査内容：Karnofsky Performance Status （KPS）と社会復帰状況を調査した。【結果】 KPS：VAD 患者 64.7±16.4（植、移植後患者 97.4±6.1 であっ込型 69.5±10.9、体外設置型 38±4.5）た。2）社会復帰：VAD 患者では復職・復学（主婦を含む）48.8%、休職 25.6%、退職 25.6% であった。移植後患者では復職・復学は 70.7%、就職準備中 25.9％、無職 3.4％であった。【結語】心臓移植後患者の QOL は良好で社会復帰も可能であったが、 VAD 患者では、植込型における QOL は、体外設置型と比べて改善するが、社会復帰が課題である。プログラム・抄録集シンポジウム２０（S20）心不全と弁膜症 S20-1 Non-pharmacological Therapy for Functional Mitral Regurgitation Makoto AMAKI、Akira FUNADA、Hiroyuki TAKAHAMA、Takahiro OOHARA、 Takuya HASEGAWA、Yasuo SUGANO、Masanori ASAKURA、 Hideaki KANZAKI、Masafumi KITAKAZE、Toshihisa ANZAI National Cerebral and Cardiovascular Center Severe mitral regurgitation（MR）is a frequent complication of end-stage cardiomyopathy that contributes to heart failure and predicts a poor survival. The mechanisms of functional MR are not fully understood, though several factors are proposed.（1）Mitral annular dilatation and papillary muscles displacement due to left ventricular（LV）remodeling will lead to restricting leaflet motion toward closure.（2）Impaired LV systolic function decreases transmitral pressure force acting to close the mitral leaflets. Despite surgery is the gold standard therapy for degenerative MR, surgery for functional MR is controversial as the MR is the consequence and not the cause. Bolling ﬁrst demonstrated surgical improvement in LV ejection fraction and decrease in end diastolic volumes in patients with functional MR over 3 to 5 years. There was also improvement in functional class in his series of patients. However, there has been no randomized trial for the treatment of functional MR. Moreover recent reports show no long term survival beneﬁt of adding mitral annuloplasty to coronary bypass graft surgery. Percutaneous therapies for secondary MR have generated much interest, and many different percutaneous technologies are being developed. Future data from randomized trials will help clarify when and in whom these therapies are applicable. The purpose of this session is to review and to seek for the further possibility of non-pharmacological therapy to functional MR. S20-2 S20-3 Indication of Mitral Valve Plasty or Replacement for Functional Mitral Regurgitation in Non-Ischemic Dilated Cardiomyopathy Joji HOSHINO、Tadashi ISOMURA Hayama Heart Center ObjectiveBecause functional mitral regurgitation （FMR） causes by not only annular dilatation but also mitral （MVP） for FMR required both tethering, mitral valve plasty annuloplasty and correction of sub-valvular lesion including papillary muscle plication or second chordal cutting. We reconsidered the indication of MVP or replacement （MVR）for FMR in non-ischemic cardiomyopathy（DCM）. Patients and methodsBetween 2008 and 2013, we operated 118 patients with DCM. MVP was performed in 95, MVR in （SVR） in 69 patients. 23, and surgical ventricular restoration The patients were divided into two groups（ MVP-group and MVR-group）and relationship between left ventricular dimension（LVDd）, volume（ESVI）, ejection fraction（EF）, E/e, degree of MR, EROA, LVMI, af, concomitant SVR and the difference of operative technique for FMR was analyzed.ResultsThe concomitant SVR was performed more in patients with MVP than those with MVR. However, the LVDd,EDVI, EF,E/e,EROA, degree of MR,LVMI, af showed no statistical differences between two groups. ConclusionSurgery for FMR in DCM, MVP is indicated in patients with SVR, however, MVR is indicated in mitral procedures without SVR. S20-4 Papillary Head Optimization for Functional Mitral Regurgitation Norio TADA Masashi KOMEDA1）、Tatsuya OZAWA1）、 Minoru MATSUHAMA1）、Shinji MASUYAMA1）、 Hideki KITAMURA2）、Kiyoshi YOSHIDA3）、Takehiro OHTA4） Cardiology, Sendai Kousei Hospital, Sendai, Japan MitraClip is a percutaneous treatment of mitral valve regurgitation（MR）with edge-to-edge repair based on surgical Alﬁeri technique concept. This is a less invasive therapy without a need of open-heart surgery and cardiopulmonary pump. Clinical trials have shown MR reduction and symptom improvement after MitraClip procedure. MitraClip is expected to be an alternative therapeutic option for heart failure with functional MR and early introduction to Japan is warranted. 1） Cardiovascular Surgery, Kansai Heart Center, Takanohara Central Hospital, Nara, Japan、2）Cardiovascular Surgery, Nagoya Heart Center, Nagoya, Japan、3）Cardiology, Sakakibara Hospital, Okayama, Japan、 4） Cardiology, Kansai-Heart Center, Takanohara Central Hosiptal, Nara, Japan [Background] Reparative surgery for functional mitral regurgitation （MR）sometimes suffers from late recurrence. Tethering of the posterior leaflet is a major cause which facilitated us to develop papillary head optimization（PHO）.[Method] 38 patients（mean age 68, 27males）who had elective PHO where both papillary heads were connected in each papillary muscle and resuspended anteriorly in the past 4 years were studied in: LVDd, LVEF and MR by echocardiography at preoperative, postoperative before discharge, and late postoperative（ mean 456 days）time. They were divided to 3 groups and were analyzed.[Results] There was no hospital death.1）Ischemic FMR（IMR Group,12pts）; LVDd changed from 62mm （preop.）to 58（late postop.）, LVEF from 27% to 32, and MR from 3.5 to 1.6（p<0.01）. There was no redo and no late death.2）Non-ischemic FMR（FMR Group,16pts）; there was 1 reoperation and one late death. LVDd improved from 64 to 56, EF from 24 to 35, MR from 3.4 to 1.4（all p<0.01）.3）MR due to secondary DCM（Secondary MR Group,10pts）: LVDd improved from 64 to 50,EF from 42 to 55,MR from 3.3 to 1.3 （all p<0.01）without late death.[Conclusions] PHO showed excellent results after the surgery. However, in ischemic group LV function did not improve signiﬁcantly. Also, there was a redo case in non-ischemic group which shows necessity of further improvement for sick patients. 171 シンポジウム Percutaneous Mitral Valve Repair for Functional Mitral Regurgitation: MitraClip 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society シンポジウム２１（S21）緩和ケア S21-1 S21-3 非がん疾患に対する緩和ケア 1） 2） 2）木澤義之、坂下明大、山口崇、余谷暢之病院における心不全患者の緩和ケアの現状と課題 2）神戸大学大学院医学研究科先端緩和医療学分野、2）神戸大学附属病院腫瘍センター緩和ケアチーム 1）緩和ケアとは、「生命を脅かす病に関連する問題に直面している患者と家族に対し、痛み、その他の身体的、心理社会的、スピリチュアルな問題を早期に同定し、適切に評価し、対応することを通して、苦痛を予防し緩和することにより、患者と家族の Quality of Life を改善する取り組みである」とされている。緩和ケアの専門性は、まさに「症状緩和」と「Death and Dying（死にゆく人をどう支えるか）」双方にある。我が国においては、西欧諸国と同様に 1980 年代よりホスピス・緩和ケア病棟からその普及が始まりがん医療を中心に発展してきた。しかしながら、緩和ケアの対象はがん患者・家族だけではない。また、非がん患者にも痛をはじめとした様々な身体症状や気持ちのつらさがあり、緩和が必要であることが種々の研究から明らかとなってきている。本演題では、非がん疾患の緩和ケアの特徴を述べ、実際にどのように臨床実践を行っていったらよいかについて考察する。特に診断時からの意思決定支援と終末期ケアに焦点を当てて論じていきたい。 S21-2 当院での取り組みから見る心不全における緩和ケアの解決すべき課題シンポジウム大石醒悟 1）、宮田大嗣 1）、大西哲存 1）、谷口泰代 1）、田中奈緒子 2）、川合宏哉 1）兵庫県立姫路循環器病センター循環器内科、2）兵庫県立姫路循環器病センター看護部 1）当院は循環器専門病院として多数の循環器診療に携わっているが、2011 年以降取り組むべき課題として心不全の緩和ケアについて学習し、臨床現場で実践している。取り組みの中で、長期に渡る経過を説明し、希望と現実を患者側、医療者側で調整し意思決定を行う、アドバンスケアプランニングが悪性腫瘍のみならず慢性心不全にも十分に適応可能で、かつ緩和ケアの実践に最も重要であるという認識に至っている。一方で慢性心不全における緩和ケアの実践には解決すべき課題は非常に多いことを実感しており、本発表では、アドバンスケアプランニングの障壁（患者・疾病関連、医療者関連、医療連携等の社会資源関連）を中心に課題を挙げ、問題意識を共有しその解決法を検討することで本シンポジウムが心不全における緩和ケア推進の一助となることを期待する。 172 河野由枝国立循環器病研究センター循環器疾患は、心移植をはじめとする高度医療やデバイスの進歩により心疾患患者の予後は延長している。予後の延長は、慢性心不全患者の増加を意味し、増悪と軽快を繰り返しながら末期に至るという病みの軌跡を踏まえて、心疾患とともに生きていく患者とその家族を支える関わりが求められている。しかしながら現状は、ACP（advance care planning）がなされておらず、それは患者自身がエンドオブライフケアについて考える機会を阻み、セルフケアアドヒアランスの低下に繋がっていると考える。また、急変時には患者の意向がわからず、家族や医療者に倫理的なジレンマを生じさせる。このような状況の中、当センターでは ACP と終末期医療を支援することを目的に、循環器緩和ケアチームを発足させた。 ACP の実施とその教育、末期の症状マネジメント（麻薬の使用・鎮静のあり方など）や治療の差し控え・DNAR などの倫理的問題に対して主治医チームとともに患者の QOL の維持・向上を目指して活動している。腎機能障害の多い心疾患患者に使用できる麻薬がない、長期療養を強いられている強心剤持続点滴患者の在宅療養などの課題に対する検討が必要である。 S21-4 心不全の在宅看取り弓野大、星敬美、伊東紀揮、吉田真希、堀部秀夫ゆみのハートクリニック末期心不全患者の end of life をどのようにマネージメントするかがこれからの循環器医療の大きな課題となっている。末期心不全患者は、高度医療機関に外来通院し、増悪の度に救急搬送され、長期入院している現状がある。この背景には、高齢化、先進医療の普及とともに、独居や認知症、併存疾患の合併が多い高齢者心不全の地域での受け皿が整っていないという現状がある。このため心不全患者を外来診療から訪問診療、在宅での看取りまで、包括的かつ一連の管理を行う施設が求められている。当院は、都心部で心不全患者を多職種で包括的に管理することを目指し、外来から在宅訪問診療までを行っている。本セッションでは、現在われわれが取り組んでいる心不全患者の在宅管理、その中でも在宅看取りに焦点をあて、様々なケースから問題点を提示し、これらの心不全医療の一助になるよう議論したい。プログラム・抄録集シンポジウム２２（S22）循環器領域におけるビッグデータの作り方 S22-1 Future Directions in Heart Failure Registry in Japan Hiroyuki TSUTSUI Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan Heart failure （HF） registry is essential to describe the clinical epidemiology of HF patients and assess the diagnostic and therapeutic processes. However, the cohort of HF patients is diverse in terms of age, sex, etiologies, medical history, clinical characteristics, treatment, and outcomes. To translate the information obtained from HF registry to better patient care, it is essential to standardize the framework of registry including 1）screening and recruitment, 2）demographics, 3）previous cardiac diagnosis, risk factors, medical history, 4）acute presentation（clinical characteristics）, 5）test reporting and observation care, 6）patient course including response to treatment, 7）outcomes, and 8）follow-up period and establish the consistent database of patient selection, demographics and medical history of eligible patients, intervention or evaluation protocols, outcome measures, and time intervals for measurements. It is also essential to combine the clinical data in the clinic and/or hospital with the daily life data including physical status, diet, and exercise during work and at home. With the accumulation of such data, big data computing and research would be possible in HF. We need to improve the interpretability of research in the future HF registry and contribute to the improved patient care through better application of evidence-based medicine. S22-2 Nationwide Registry of Heart Failure with Preserved Ejection Fraction-JASPER Study Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center Heart failure with preserved ejection fraction（HFpEF）is unresolved and growing public health problem. Previous randomized clinical trials have failed to show the beneﬁcial eﬀects of cardiovascular drugs, which can improve clinical outcomes in patients with heart failure with reduced ejection fraction（HFrEF）. Although heterogeneous condition consisting of multiple co-morbidities has been postulated as the cause of the negative results, the precise pathophysiology of HFpEF remains to be elucidated. In addition, previous clinical trials targeted outpatients with HFpEF, rather than hospitalized patients with acute decompensated heart failure（ADHF）. To clarify the actual condition of HFpEF, we started nationwide web-based registration of HFpEF（JApanese heart failure Syndrome with Preserved Ejection fRaction [JASPER] study）among patients with hospitalized ADHF since 2012. Patients with EF >=50% or fractional shortening >=25% admitted to nationwide core institutes are included for the study population. The interim data showed that most patients with this registry had severe diastolic dysfunction, in contrast to the results of sub-analysis of I-PRESERVE study showing only 4% of the study population had severe diastolic dysfunction. By including hospitalized ADHF patients in core institutes, HFpEF population became less heterogeneous and the distinctive pattern of acute exacerbation in HFpEF patients has been clarified. Such information may contribute to clarify the eﬀective treatment for real HFpEF and to identify patients responsible for such treatment. Introduction of the Clinical Eﬃcacy Evaluation Registry Facilitated by MCDRS and CAIRS Takahide KOHRO Department of Clinical Informatics, Jichi Medical University, Tochigi, Japan Background Recently, electronic health records（EHR）systems are increasingly introduced into Japanese hospitals, especially large or educational ones. This means that in such hospitals, most clinical information is recorded digitally. However, usually when doctors and researchers want to use this information, they have to manually type the information again into another computer. This is not only cumbersome but also leads to errors.Methods We had developed a data registry system, which enables researchers to collaborate over 'the cloud'. Beginning this April, we started improving the system whereby data can be obtained not only through manual typing but half-automatically from EHR systems. This is done by ﬁrst exporting EHR data into SSMIX2（which stands for Standardized Structured Medical record Information eXchange）format. As for coronary angiography and interventional data, data is stored and provided through the Coronary Angiograph and Interventional Report System （CAIRS）, which we had developed.Results The registry system, called MCDRS（which stands for Multi-purpose Clinical Data Repository System）is still in development. However, clinical data is collected through usual clinical practice. Our initial primary target diseases are coronary artery disease and heart failure. We plan to analyze these data combined with hospital administration data to evaluate not only clinical questions related to these diseases but also cost-eﬀectiveness of several treatments. S22-4 Three Key Issues to Lead a Valuable "Big Data": Suggestion from the experiences of the Registry Naoki SATO Cardiology and Intensive Care Unit, Nippon Medical School MusashiKosugi Hospital Cardiovascular diseases, especially heart failure, are a major and growing public health burden and the leading cause of hospitalization. To improve the present critical condition such as "heart failure pandemic", we should create "big data" and analyze it. We conducted the high-quality of registry, the ATTEND（acute decompensated heart failure）registry, which was started from 2007 and ﬁnished at a follow-up rate of 99.8%. From our experiences in the ATTEND registry, we would like to suggest the following three key issues to lead a valuable "big data": 1）appropriate data contents, 2）easy data collection, 3）speedy data analysis. First, the data content should be minimum and essential. Don t add too much additional contents except the data inputted automatically, otherwise it leads to wrong interpretations by lots of missing data. Second, the easiest way to collect the data should be created in the position of an inputting person. The system which transfer the data automatically to the database should be built. Third, the fastest way to analyze should be developed by good statisticians and engineers. These three points should be consider to create a valuable and useful "big data" in the cardiovascular ﬁeld. 173 シンポジウム Toshihisa ANZAI、Toshiyuki NAGAI、Yasuo SUGANO、 Takahiro OHARA、Hideaki KANZAKI、Yasuhide ASAUMI、 Teruo NOGUCHI、Kengo KUSANO、Satoshi YASUDA、Hisao OGAWA S22-3 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S22-5 Large-Scale Registry Study of Patients with Chronic Heart Failure-Lessons From the CHART-2 StudyHiroaki SHIMOKAWA Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Background: Evidence-based medicine is important to improve the prognosis of patients with chronic heart failure（CHF）. To obtain informative evidence to develop effective treatment for HF, some diﬀerent types of big data have been accumulated in cardiovascular research area. We have successfully enrolled 10,219 consecutive CHF patients in our Chronic Heart failure Analysis and Registry in the Tohoku District-2（CHART-2）study. Method: The CHART-2 study is a prospective, observational, and multicenter cohort study to elucidate the characteristics, mortality and prognostic risk of CHF patients in Japan. In this large-scale study, a server computer, which was accessible at any time through internet, was used to build a multicenter clinical research network database.Results: To conduct the CHART-2 study, the Tohoku Heart Failure Association was established in collaboration with 24 hospitals. The database was designed so that the privacy of patients was protected by removing personal information. The collected data were cleaned up for data mining and knowledge discovery. To collect, manage, and analyze the stored data, it was necessary to secure qualiﬁed specialists including clinical research coordinators, data managers, and biostatisticians. These specialists contributed to the design of the study protocol, written informed consent, and data analysis. Conclusions: To make big data from a large-scale cohort study, collaboration with specialists in various areas is important. シンポジウム 174 プログラム・抄録集シンポジウム２３（S23）心不全患者の栄養管理はどうする？ S23-1 S23-3 今どきの心不全診療では栄養管理に何を求めるのか？心不全とサルコペニア猪又孝元絹川真太郎 1）、福島新 1）、眞茅みゆき 2）、筒井裕之 1）北里大学医学部循環器内科学 1）循環器疾患におけるこれまでの栄養管理とは、制限をかけることであった。すなわち、動脈硬化予防としての脂質管理、糖質管理、体重管理に向けての食事療法である。しかし、 obesity paradox の報告以来、特に心不全の領域での低栄養が注目され始めた。さらには、いわゆるカヘキシーがサルコペニアやサイトカイン過剰を通じて心不全予後を左右している事実が判明した。しかし、現場での介入法については、研究がようやく緒に就いた段階で、具体的実践にはまだほど遠い。一方で、実際の栄養指導の現場では、心不全患者に行われる指導内容のほとんどが減塩である。患者指導でのニーズも極めて大きいことを実感する。しかし、不思議なことに、臨床栄養に関する学会などで減塩が語られる機会は少ない。その理由のひとつとして、高血圧領域と異なり、心不全での減塩のエビデンスは意外にも少なく、臨床の現場でどのように減塩を実践すべきかが一般化されていないことがあげられる。それに加え心不全管理において、最近では特に急性期管理での減塩が治療予後を改善していない事実や、尿中 Na 測定の臨書的意義の不確かさが指摘されている。現在の心不全管理は、臨床的意義が多方面に広がり、ときに理解が困難にすらなっている。予防に始まり、心不全予後、さらには心不全徴候と、それぞれ有効な治療内容が異なることすらある。そのような現況を鑑み、心不全管理の基本を押さえ、心不全患者における栄養管理について概説する。本邦および欧米の疫学研究で、心不全における Obesity Paradox と言われる現象が観察されている。すなわち、心不全患者では肥満を有する方が予後良好であった。しかしながら、これは痩せていることが予後不良と密接に関わっていると考えるべきである。痩せの要素の中で、筋肉は重要であると考えられる。筋力の低下や筋量の減少が心不全患者の予後悪化と密接に関連しているばかりでなく、日常生活動作の低下や QOL の低下をもたらすことが報告されている。加齢に伴う筋肉量の減少および筋力の低下をサルコペニアと呼ぶが、心不全患者でもサルコペニアと同等の状態を呈する患者の割合が高い。一方でこのような筋肉減少を引き起こす原因はまだはっきりと示されていない。重症心不全患者では食欲低下，安静時エネルギー消費量の増加，消化管吸収能障害，腎機能障害，肝機能障害から低栄養状態となり得、サルコペニアの発症とも関連している可能性がある。我々の最近の検討では、心不全患者における骨格筋萎縮と栄養状態の指標が密接に関連することが示された。したがって，栄養状態および筋肉量，筋力を適切に評価し介入方法を探究することが必要であると考えられる。 S23-2 高齢患者における摂食嚥下機能清水洋子鳥取大学医学部付属病院リハビリテーション部 S23-4 心不全患者の栄養サポートにおける管理栄養士の今後の展望宮島功、宮澤靖近森病院栄養サポートセンター我が国の高齢化率は増加の一途をたどっている。高齢化の進行は心不全の増加に反映するとされ、JCSRE-CARD 研究において、心不全患者のうち 80 歳以上の占める割合は 28.6％であった。高齢心不全患者の問題は、合併症や認知症が多い、骨格筋の減少、ADL の低下など様々である。また、慢性心不全などの慢性疾患による悪液質（カヘキシア）が低栄養状態を進行させる。さらに、高齢者では生理的に腎機能低下を認め、近年では心不全患者での腎機能が予後予測因子となることが明らかとなり、心腎症候群の考えが広まっている。従来、心不全患者の栄養サポートは「減塩・水分管理」が主であった。しかし、高齢心不全患者が増加する現在では、「減塩・水分管理」を基本とし「栄養状態の維持・改善」「心不全の再発・、再入院予防」「合併症の増悪予防」、を目的に、管理栄養士も個々の患者の病態、病期、基礎心疾患を把握した上で、適切な栄養アセスメントのもと早期からの適正な栄養サポートが重要であると考える。心不全患者における栄養サポートについての報告は少なく、今後さらなる発展が必要である。 175 シンポジウム摂食嚥下とは、食べ物を認識し、口に入れて咀嚼し食塊を作り、それを口腔から咽頭、食道、胃へと送り込むための一連の運動であるとされる。摂食嚥下障害の原因疾患は、神経疾患、頭頸部疾患等が挙げられているが、高齢者においては、更に誘発要因としてあげられるものが多くなる。加齢に伴う様々な機能低下とあわせ、近年原発性サルコぺニア（筋肉量減少と筋力の低下）、二次性サルコぺニア（加齢以外を起因としたもの）が述べられるようになり、栄養、運動の大切さが注目されるようになった。嚥下関連筋群（舌、舌骨上筋群）にもサルコぺニアが起こると言われて久しい。加齢による機能低下は個人差が大きく少しずつ低下していくため、環境と機能は順応し日常生活を送る中でも大きな問題なく過ごすことができることが多い。しかし、何らかのきっかけで二次性サルコぺニアの状態に陥った時、嚥下機能の低下が起こってくる。そのため、虚弱高齢者では明らかな直接的原因がなくても、急性疾患で入院し安静加療、絶食を経て食事再開したときに誤嚥を呈することがある。ここでは、高齢患者の摂食嚥下障害の特徴と対応、リハビリについて概説する。北海道大学大学院医学研究科循環病態内科学、2）北里大学看護学部第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society S23-5 心不全患者における栄養評価中屋豊公立学校共済組合四国中央病院臨床研究センター我が国では血清アルブミン値（Alb）が栄養状態の指標として用いられることが多い。しかしながら、Alb は炎症、肝疾患、代謝亢進など栄養以外の因子の影響を受け、栄養状態を表す良い指標でない（Alb を用いた栄養評価指標なども）。心不全でも、Alb は体水分量、肝うっ血、腸管からの蛋白漏出、炎症などの影響を受け、栄養状態よりもむしろ疾患の重症度を反映する。そのため、予後を見る指標としては良いが、栄養状態の評価や栄養補給の効果の判定には不向きである。SGA などの栄養評価ツールでは、体重減少および BMI の低下、特に筋肉の減少が栄養評価で重要な項目であるが、心不全においては浮腫、胸水などの影響があり、正確に評価することが困難なことが多い。現在、栄養状態を評価する最も良い指標とされているのが、体細胞量および筋肉量である。これらの計測には DEXA （浮腫の無い例ではインピーダンス法も）が有用であるが、これらは特殊な機器を必要とする。身体計測や歩行能力などによる筋肉の量や機能についての計測も行われる。このように、心不全の栄養評価では単独では良い指標がないため、多くの所見に基づき総合的に判断する必要がある。シンポジウム 176 プログラム・抄録集シンポジウム２４（S24）心不全における他臓器連関 S24-1 Heart Failure as a Whole Body Disease. Stefan D. ANKER University Medical Center, Göttingen, Germany Chronic heart failure（CHF）is a complex disease aﬀecting many body systems. It involves neurohormonal activation, endothelial dysfunction, inﬂammation, liver dysfunction, anemia and iron deﬁciency, as well as metabolic changes including insulin resistance and skeletal muscle wasting and cachexia. These abnormalities are interlinked. One theory linking several of these abnormalities is the Endotoxin Hypothesis of inﬂammation in CHF. Patients with CHF develop gut abnormalities leading to impaired permeability, local ischemia and gut oedema. When this develops, bacterial endotoxin （i.e. LPS）may cross the gut barrier and when it is then insufficiently cleared from the blood stream in the liver, increased amounts of LPS can cause inflammation. Also in situations where no absolute increase of LPS is observed, this may still be an important trigger of inﬂammation in CHF because neurohormonal activation can ‒ amongst many things ‒ cause increase endotoxin sensitivity of immune competent cells. Also this will result in tissue inﬂammation. Consequences of tissue inflammation are also anemia and iron deficiency, as has been shown in several studies. CrP and hepcidin are important mediators of changes in iron uptake and tissue storage, resulting in development of functional iron deﬁciency. Lastly, wasting process accompanied by development of abnormal insulin sensitivity and resulting in lipolysis and muscle wasting can result from this cascade of metabolic changes. We believe, that therapeutically targeting these abnormalities will be useful. Clinical developments are underway. S24-2 S24-3 Heart Failure as a Dysfunction of Dynamic Circulatory Homeostasis Mediated by Brain "Astrocyte" Just Like Central Processing Unit Takuya KISHI Department of Advanced Therapeutics for Cardiovascular Diseases, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan Circulatory homeostasis is associated with interactions between multiple organs, and dysfunction of dynamic circulatory homeostasis is considered to be heart failure. Recently we showed that arterial baroreflex failure induces striking volume intolerance indeoendent of left ventricular（LV）dysfunction and steepens the renal pressurediuresis relationship. These results strongly suggest that brain mediates the dynamic circulatory homeostasis. We also have demonstrated that angiotensin II type 1 receptor（AT1R）-induced oxidative stress and /or inﬂammation mediated by toll-like receptor 4 in the rostral ventrolateral medulla（RVLM）, which is known as a vasomotor center, causes prominent sympathoexcitation in heart failure model rats. In the brain, astrocytes are more abundant than neurons, and normal astrocytes have little AT1R. However, targeted deletion of AT1R in astrocytes strikingly improved survival with prevention of LV remodeling and sympathoinhibition in myocardial infarction-induced heart failure. Moreover, AT1R-induced oxidative stress and tumor necrosis factor α-induced antioxidant nuclear factor erythroid 2-related factor 2 dysfunction decreased astrocytes in heart failure. These results indicate that AT1R in astrocytes, not in neurons, have a key role in the pathophysiology of myocardial infarctioninduced heart failure. We would like to rise a new concept that astrocytes work as a central processing unit integrating neural and hormonal inputs into the brain, and that the dysfunction of dynamic circulatory homeostasis mediated by astrocyte causes heart failure. S24-4 Cardio-Respiratory Coupling, Pulmonary Hypertension and Cardiac Function Hiroshi ASANUMA1）、Hiroyuki TAKAHAMA2）、Miki IMAZU3）、 Hideyuki SASAKI3）、Madoka IHARA3）、Tetsuo MINAMINO4）、Seiji TAKASHIMA5）、 Masaru SUGIMACHI6）、Masanori ASAKURA2,3）、Masafumi KITAKAZE2,3） Akihiro HIRASHIKI1）、Takahisa KONDO1）、 Toyoaki MUROHARA2） Department of Cardiovascular Science and Technology, Kyoto Prefectural University School of Medicine, Kyoto, Japan、2）Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan、 3） Department of Clinical Research and Development, National Cerebral and Cardiovascular Center, Osaka, Japan、 4）Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan、5）Department of Medical Biochemistry, Osaka University Graduate School of Medicine, Osaka, Japan.、6）Department of Cardiovascular Dynamics, National Cerebral and Cardiovascular Center, Osaka, Japan 1） Hyperphosphatemia is found in the majority of patients with end-stage renal disease. Recent studies have also documented that hyperphosphatemia is associated with cardiovascular diseases and increases both mortality and morbidity, and we found hyperphosphatemia in patients with chronic heart failure（CHF）and a signiﬁcant positive correlation between serum phosphate levels and plasma BNP levels. Therefore, we tested whether precipitated calcium carbonate, a drug for hyperphosphatemia, mediates beneficial effects on left ventricular dysfunction in the canine pacing-induced heart failure model. In beagle dogs, we induced heart failure by 6 weeks of rapid right ventricular pacing at 230 bpm using a pacemaker with or without precipitated calcium carbonate at a daily oral dose of 100mg during forth to sixth week. Neither blood pressure nor heart rate at basal conditions diﬀered between the groups treated with and without precipitated calcium carbonate 6 weeks after the onset of the study. Left ventricular ejection fraction increased, and both mean pulmonary arterial pressure and pulmonary capillary wedge pressure decreased in the precipitated calcium carbonate-treated group compared with the untreated group. The administration of precipitated calcium carbonate decreased plasma phosphate levels compared with the untreated group. Thus, we conclude that the reduction of serum phosphate levels is beneﬁcial for the pathophysiology of CHF and may provide an important novel therapeutic target in patients with CHF. 1） Department of Advanced Medicine in Cardiopulmonary Desease, Nagoya Graduate School of Medicine, Nagoya, Japan、2）Department of Cardiology, Nagoya Graduate School of Medicine, Nagoya, Japan The severity of exertional dyspnea during daily life is difficult to determine through outpatient interviews or measures obtained during the resting condition. Objective parameters are essential for assessing exercise capacity and cardiopulmonary reserve, especially for patients with severe heart failure, including pulmonary hypertension（PH）and severe chronic heart failure reduced ejection fraction （HFrEF）.For evaluating these patients, the 6-minute walking distance, though used frequently, is not suﬃciently accurate. To increase assessment accuracy in patients with PH or HFrEF, we perform cardiopulmonary exercise testing（CPX）. In patients with pulmonary arterial hypertension at baseline and 3, 6, and 12 months after PAH-speciﬁc treatment, mean peak VO2 was 11.99, 13.70, 14.60, 14.97 mL/kg/min and VE/ VCO2 slope was 61.0, 50.9, 49.5, and 43.6, respectively. CPX was performed without adverse eﬀects in all patients with PH （mean pulmonary arterial pressure > 25 mmHg; n=95）or left heart disease（n=377）, except for 1 patient with PH（1.05%）, who experienced transient supraventricular tachycardia just after exercise, and 1 patient with HFrEF（0.26%）, who had transient low blood pressure due to a stress-induced vasovagal reaction. We recommend early initiation of routine CPX testing to monitor disease severity and progression and therapeutic eﬀects in patients with PH or HFrEF. 177 シンポジウム Development of New Heart Failure Treatment in Consideration of Cardiorenal Syndrome 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society 教育講演１（EL1）塞後心不全のTR研究（EPO-AMI-II試験）南野哲男大阪大学大学院医学系研究科循環器内科心筋塞は急性期死亡率が依然高い疾患である。また、塞後慢性期には心不全へ進展するため、急性心筋塞に対する新しい治療法の開発は重要なアンメットニーズである。私たちは、大型動物を用いた基礎研究において、エリスロポエチンが心筋細胞死を抑制し、同時に血管新生を促進する結果、塞後慢性期心機能を著明に改善することを報告した。さらに、急性心筋塞患者（41 名）を対象とした臨床試験において、心筋塞急性期におけるエリスロポエチン静脈内単回投与により慢性期心機能が著明に改善することが明らかになった（EPO-AMI-I 試験）。そこで、急性心筋塞患者に対する EPO 投与による慢性期心機能改善効果を検討するため、多施設共同プラセボ対照無作為化二重盲検並行群間比較試験（EPO-AMI-II 試験）を開始した。本研究は、全国 26 施設が参加し、低心機能（左室駆出率 50% 未満）をともなう初発急性心筋塞患者を対象とする。主要評価項目は、心筋シンチにより評価した慢性期左室機能改善効果である。本研究では、急性心筋塞患者を対象とする " 質の高い " 臨床試験を実践し、日本発の治療法の創出をめざす。教育講演２（EL2）成人先天性心疾患における心不全の多様性および治療の実際と問題点に関して八尾厚史東京大学保健・健康推進本部教育講演先天性心疾患（CHD）に対する外科的手術の進歩により、現代では出生率 1% で誕生した CHD 患者のほとんどは成人化する。そして、手術により修飾を受けた新しい疾患群成人先天性心疾患（ACHD）が形成されている。 ACHD において、最も大きな問題の一つが心不全である。その治療指針は多くが経験的なものであり、薬物治療に関しては一般の心不全に比べて重要視されてはいない。さらに、ドナー不足やその解剖学的特性もあり、最終的な手段である心臓移植も本邦ではほとんど施行されていない。この問題に関しては、多臓器不全例が多いこともあり、今後も心臓移植に持ち込める例はかなり限りがある。本教育講演では、ACHD 心不全に関して病態を大きく 5 つに分けて解説をしてみたい。すなわち、体心室左室・右室不全、肺心室左室・右室不全、単心室循環不全である。これらの病態での治療に関して総論的に言及することとする。また、すべての ACHD 病態に関して述べるのは不可能であるため、今回は Fallot 四徴症術後を例に、どういった心不全が発生し、どう治療していくのかに関して解説を試みる。疾患・修復術特異的な心不全発症機序とその治療の概略を理解いただければ幸いである。 178 プログラム・抄録集教育講演３（EL3） BNP：発見、発展から未来へ南野直人国立循環器病研究センター研究所分子薬理部 1988 年の BNP 発見から 25 年が過ぎた。発見当初は神経系で作動するペプチドと推定されたが、その後の研究により、BNP も ANP と同様に心臓より産生・分泌されるペプチドホルモンであることが明らかとなった。さらに、圧・容量負荷による産生亢進、血中濃度の変動は BNP が ANP を凌駕し、心不全の診断マーカーとしては ANP に優ることが証明され、世界で汎用されるに至った。発見から診断法確立における研究において、日本人の貢献は極めて大であった。 BNP については、新しい事実も積み重ねられている。心不全重症化により proBNP の増加が報告されているが、この原因が proBNP への糖鎖付加亢進に由来し、糖鎖の立体障害により低活性の proBNP から活性型 BNP-32 への変換が阻害されると推定されている。そこで、京大の錦見らと共同し、proBNP と BNP-32 比率などが診断マーカーとならないか検討を行っている。他の報告も含め、ここ 5 年程で BNP 研究が再活性化してきた感がある。本講演では、同じ受容体に作用する ANP と BNP、そして多様な内在分子型と活性強度、循環制御や診断について、生化学的な立場からお話ししたい。教育講演４（EL4）経皮的左心耳閉鎖術松本崇仙台厚生病院心臓血管センター 179 教育講演心原性脳塞栓症は心房細動患者の生命を脅かす重要な合併症である。従来、その予防目的に経口抗凝固薬投与を原則として生涯にわたり施行してきた。しかし、その有効性に疑いはないものの長期投与による出血性合併症は大きな課題と考えられている。その一方で、近年、心房細動患者の脳塞栓症予防目的に経皮的左心耳閉鎖術が登場した。心原性脳塞栓症を引き起こす血栓はその約 9 割が左心耳に発生すると報告されており、左心耳を閉鎖することで心原性脳塞栓症を防ぐのが本治療法のコンセプトである。本演題では経皮的左心耳閉鎖術の治療の実際、主要臨床試験の結果、そして欧米での動向を概説したい。第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society 教育講演５（EL5）心不全の病理羽尾裕之兵庫医科大学病院病理部心不全では心筋の肥大・変性・脱落が起こる。このような過程で傷害を受けた心筋細胞は核の大型化や異常切れ込み像・心筋細胞径の増大や狭小化・心筋細胞の配列の乱れや分岐異常が認められる。正常心では心筋細胞の配列や構造保持にコラーゲン等の細胞外基質が重要な役割を果たしている。心不全を引き起こす心筋塞・心肥大・心筋症などでは、心筋の瘢痕化や間質の線維化に細胞外基質の代謝が関与し、病態と密接に関連している。心不全末期では細胞外基質による心筋細胞の保持機能の喪失により、心拡大が起こる。また心臓には心筋細胞以外にも線維芽細胞・血管平滑筋細胞・内皮細胞・脂肪細胞などの細胞成分が含まれており、これらの細胞も心臓のリモデリングに関与している。心不全では全身臓器へも様々な影響を与え、これらの臓器障害が予後を規定する場合も多い。本教育講演では剖検症例や心筋生検材料を用いて、心不全を引き起こす様々な病態における心筋組織の形態学的な変化のマクロ・ミクロ像を呈示したい。また心不全動物モデルを用いた自験例のデータの一部を含めて、心筋リモデリングの分子メカニズムについても言及する。教育講演６（EL6）非侵襲的陽圧換気療法（NPPV）で患者を救うために覚えておきたいこと渡邉雅貴東京医科大学循環器内科教育講演 1980 年代の後半より、呼吸器疾患、特に慢性閉塞性肺疾患領域で開発が進められていた NPPV は心不全治療に用いられるようになった。特に急性心不全の際にみられる低酸素血症は、当初気管挿管の回避が一義的と考えられていたが、酸素化の速やかな改善、呼吸仕事量の軽減のみならず、急性心不全の際の不安定化した血行動態の改善にも寄与するこが知られるようになり、ﬁrst line therapy となっている。現在本邦で用いられている NPPV はフローバイ方式であり、人工呼吸器に比べて気道・肺胞損傷のリスクが低く、人工呼吸関連肺炎の発症も発症も少ないと期待されている。しかしながら NPPV は非侵襲的ながらしっかりと急性心不全患者においても十分に前負荷を軽減することができます。また、NPPV による胸腔内陽圧化は収縮期の左室 transmural pressure を減ずることにより後負荷を減らすことができる。これは前方拍出の増加をもたらし、心不全治療としては理にかなったものである。本教育講演では、NPPV で心不全患者を救うために必要なメカニズムと、覚えておきたい事柄を実臨床での症例を交えながら、わかりやすく解説を行う。 180 プログラム・抄録集教育講演７（EL7）ハイリスクAS患者に対する低侵襲治療 -TAVI鳥飼慶 1）、坂田泰史 2）、倉谷徹 3）、澤芳樹 1）大阪大学大学院医学系研究科心臓血管外科、大阪大学大学院医学系研究科循環器内科、大阪大学大学院医学系研究科低侵襲循環器医療学 1） 2） 3）治療の低侵襲化の波は structural heart disease の領域にまで及んできており , その代表とも言える TAVI はハイリスク AS 患者に対する低侵襲治療として注目されている . 先進諸国では人口の高齢化から変性性の AS 患者が増加しており , 一方で人口の高齢化自体が , 患者の高齢化 , また多岐にわたる併存合併症を増加させ , ハイリスク患者の増加につながっている . 現時点における AS の標準的治療は弁置換術であるが , 開心術の適応が困難と判断されるハイリスク患者に対する低侵襲カテーテル治療として TAVI が登場したのが 2002 年のことで , 以後全世界的に急速な普及しつつある . 本邦においてもバルーン拡張型のサピエン XT と自己拡張型の CoreValve ReValving System の治験が行われ , 2013 年 10 月に前者が保険収載された . 本邦では , 安全な TAVI の普及を目的に , 関連 4 学会から構成される協議会の認定を受けた施設でのみ同手技が行われることが許されている . 致死的な術中合併症の存在や , 依然不明な長期成績等の問題はあるが , TAVI は弁膜症の治療体系を大きく変え得る有効な治療法として期待されている . 教育講演 181 第18回日本心不全学会学術集会 The 18th Annual Scientific Meeting of the Japanese Heart Failure Society ハートチーム心不全講座１（HT1）心不全ってなに？安斉俊久国立循環器病研究センター心臓血管内科心不全とは、生体の要求する血液量を心臓が拍出不可能となることによって生じる症候群と一般に定義される。しかしながら、心臓はポンプとしての機能以外に各種のホルモンを分泌し、神経体液性因子を賦活化させることによって悪循環を形成することが明らかにされ、致死的不整脈による心臓突然死も死因の多くを占めることから、近年では、心機能異常、神経体液性因子活性化、運動耐容能低下、体液貯留、生命予後不良を特徴とする症候群としてとらえられるようになった。また、一口にポンプ機能障害といっても、収縮障害だけでなく拡張障害も関与しており、病態は多様性を極めている。さらに、レニン・アンジオテンシン系をはじめとした神経体液性因子は、生命維持にとって必須の機構であるが、ナトリウム利尿ペプチドとの均衡が崩れることで心不全の発症に関与し、その背景には心臓だけでなく腎臓や脳など全身臓器との連関が考えられている。心不全とは、様々な代償機構が破綻をきたした状態であり、治療にあたっては、全身の状態を把握しながら各臓器の過剰な反応を制御し、心臓の機能回復を図ることが重要になる。ハートチーム心不全講座２（HT2）心臓MRIを用いた心不全の評価石本剛兵庫県立がんセンター放射線部心不全の評価における心臓 MRI の役割は，心機能解析と心筋性状評価である．心臓の動きを観察する cine MRI は，心エコー検査や X 線左室造影検査にはない多くの利点がある．cine MRI は，心筋と血液（心内腔）の良好なコントラストが得られるため心機能解析の再現性が高く，血流によるアーチファクトも少ないため弁をはじめ心臓形態の評価も可能である．また tagging は心筋評価だけでなく心膜炎等による心内膜癒着の評価にも有用とされている．心筋性状評価として用いられる遅延造影（LGE）モジュールの目的は，心筋塞等の虚血性心疾患や心筋症，サルコイドーシス等の非虚血性心疾患の鑑別があげられる．これらを LGE パターンから決定または除外することが LGE MRI の大きな役割である．また LGE の transmural extent を計測することにより心筋バイアビリティの評価が可能であり，さらに急性心筋塞例において微小循環閉塞（MVO）の有無は予後評価に重要な指標となる．本講演では，これらの内容を中心に心臓 MRI 検査について紹介する．ハートチーム心不全講座 182 プログラム・抄録集ハートチーム心不全講座３（HT3）心臓CTによる心不全患者の機能解析と撮影ポイント堀江誠桜橋渡辺病院放射線科近年 MDCT は、冠動脈造影検査に代わり、非侵襲的心臓画像診断法として、広く臨床の現場で使用されるようになってきた。また MDCT の多列化及び、ガントリー回転速度の高速化により、短時間で心臓全体のスキャンが可能となってきた。また得られた膨大な画像データから、画像処理技術の進歩により、形態評価である冠動脈狭窄及び、プラーク評価、機能性状評価である心機能評価、心筋性状評価など多くの情報を提供できるようになってきた。当院の機能性状評価として、左室機能評価や、ATP 負荷心筋虚血評価、心筋 viability 評価、 dyssynchrony 評価を行っており、逐次近似法による Denoise 技術によって、低電圧撮影が可能となり、使用造影剤の減量及び被ばく線量の低減で、複数回の撮影が、一度の検査で、従来の被ばく線量以下で撮影可能となった。また dyssynchrony 評価は、左室壁運動の拡張、収縮のズレを解析し、dyssynchrony の有無を判定する。また CRT ペースメーカー治療後の効果判定にも有用である。これらの当院で行っている機能解析を症例を提示しながら、また心不全患者の、撮影条件や、気をつけておかなければならないポイントなどについて議論、検討を深めたいと思います。ハートチーム心不全講座４（HT4）心不全チーム医療の重要性佐藤幸人兵庫県立尼崎病院循環器内科わが国では高齢化社会を迎え心不全患者は今後増加するものと思われる。この予測は学会や本でも取りあげられ、心不全のガイドラインでは種々の推奨度合いの高い薬剤、治療法が並んでいる。しかし、ACE 阻害薬、ARB、 β遮断薬のような class I、エビデンスレベル A の薬剤であっても医師の処方に任せていると 50% 前後の処方率という施設もいまだに多い。従来の心不全診療は、患者も内容をよく理解しておらず、生命予後改善薬は心不全診療に関心のある医師のみが処方しているという状態であった。そこで、今後クローズアップしてくるのが多職種の力、チーム医療の力である。患者自身が心不全を理解し、看護師、薬剤師、栄養士、リハビリスタッフが共通の資材を用いて入院中から通院中まで連続して状態をチェックすることにより、ガイドライン順守率は徐々に向上することが知られている。折しも慢性心不全看護認定制度が発足し、各地で卒業生たちが中心となって多職種研究会が発足し始めている。その一方で具体的な運営方法、介入点については未知の部分も多い。本セッションでは、心不全チーム医療の介入点と方向性について概論する。ハートチーム心不全講座 183