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− 北風政史会長講演

Transcription

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
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。
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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.
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
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
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
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
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
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
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.
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
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
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
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
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 postdischarge 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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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.
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
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
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
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
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
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
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
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
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
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
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.
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−
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。
シンポジウム２０（S20）心不全と弁膜症
S20-1
Non-pharmacological Therapy for Functional
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
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
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。
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
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
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
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
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
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
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
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。
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
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
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
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

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− 北風政史会長講演

Transcription

Similar documents

Shinshu University Institutional Repository SOAR-IR

SAMPLE

22646s.indd 16 2014/03/19 20:50

å¦ ç å é è¦ é

call for contribution letter

ææé²æ¢æ©è½ä»ãæ©å¨:è¡æµææ

心尖部心室瘤および持続性心室頻拍を合併した左室中部閉塞性肥大 1 Mid-Ventricular Obstructive Hyper-

ELSO-GL_Capiox_core_information

ï¼WCDï¼ã®è¨åºä½¿ç¨ã«é¢ããã¹ãã¼ãã¡ã³ã

開催の案内 - 日本歯周病学会

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− 北風 政史 会長講演

Transcription

Similar documents

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− 北風政史会長講演