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 ポスター1(P01)心肥大・心リモデリング P-001 Myocardial Afadin Contributes to Cardiac Remodeling During Chronic Pressure Overload Dimitar ZANKOV、Hisakazu OGITA Department of Biochemistry and Molecular Biology, Shiga University of MedicalScience 一般演題 ︵ポスター︶ Adaptor protein afadin and transmembrane protein nectin form cell-cell adhesion system that is essential for the embryonic development, tissue physiology, and behavior of some malignancies. In the heart afadin(paired with nectin)is located in the intercalated disks of cardiomyocytes but its function there is still unclear. We generated conditional knockout mice deficient in myocardial afadin(m-afa-/- mice)to explore the consequences of afadin loss. There was no detectable change in phenotype of m-afa-/- mice compared to littermate controls. In vivo monitoring of blood pressure, cardiac function and dimensions(echography)has not revealed significant differences. In a similar manner, heart weight, morphology, histology(HE staining), intercalated disks structure (confocal images)were indistinguishable between the two groups. Involvement of afadin in cardiac pathophysiology is evaluated in the hearts confronting pressure overload for 4 weeks by subcutaneous infusion of angiotensin II(ang). Ang treated control mice developed hypertension and cardiac hypertrophy; Massons s trichrome stained histological preparations demonstrated collagen deposits around the arterial vessels in ventricles and in some areas between myocytes. There was no deterioration of cardiac function. Hearts of ang treated m-afa-/- mice remodeled in a similar way except for the significantly less degree of fibrosis. Our data suggest involvement of myocardial afadin in cardiac remodeling during chronic pressure overload, and now underlying mechanisms are investigated. P-002 Unexpected Localization of AMPK at the Intercalated Disc Yasunori SHINTANI、Shohei YASHIROGI、Issei YAZAWA、 Seiji TAKASHIMA Medical Biochemistry, Osaka University Graduate School of Medicine, Suita,Japan AMP-activated protein kinase(AMPK)is a central player of cellular energy homeostasis. AMPK activation is triggered by energy deprivation, increased ratio of AMP/ATP. AMPK has been reported to be involved in cellular polarity, proliferation and migration, however, its substrates and downstream signalling on these cellular aspects has been unclear. We have recently established infrared confocal microscopy which enabled us to eliminate background signals from tissue section so that we can sensitively detect relatively weak signals even from phosphorylated kinase in immunohistology. Here we found an unexpected subcellular localization of AMPK at the intercalated disc in the heart by using the infrared confocal microscopy. By screening unknown substrates of AMPK at the junction fraction from the heart, we identified a couple of molecules which also localized at the intercalated disc. We confirmed these substrates were phosphorylated by AMPK in vitro and identified phosphorylation sites within them. By using phosphorylation specific antibodies, we found they were also phosphorylated at the intercalated disc by AMPK in vivo.These data propose a novel biological function of AMPK at the intercalated disc. Further investigation will be warranted. 258 P-003 Activation of PPAR Alpha During Heart Failure Maintained Myocardial Function and Energetics in Mice Transverse Aortic Constriction(TAC)Model Satoshi KAIMOTO、Atsushi HOSHINO、Yoshifumi OKAWA、 Makoto ARIYOSHI、Kuniyoshi FUKAI、Motoki UCHIHASHI、 Kazunori ONO、Shuhei TATEISHI、Eri IWAI-KANAI、Satoaki MATOBA Department of Cardiovascular Medicine, Graduate School of Medical ScienceKyotoPrefecturalUniversityofMedicineKyoto,Japan Background: Failing heart loses its metabolic flexibility and relies more on glucose as its preferential substrate. A key regulator of this substrate shift is peroxisome proliferator-activated receptorα (PPARα). However the role PPARα and the effect of modulating fatty acid oxidation(FAO)are still unclear in heart failure. Method and Results: After eight weeks of transverse aortic constriction(TAC), left ventricular function was decreased with the reduction of PPARα expression. TAC-operated mice were randomly allocated into two groups : a HF group of untreated mice with heart failure, and a WY-HF group of mice with heart failure receiving WY14643(specific PPARα agonist). Eight weeks after TAC, LV construction was preserved significantly in the WY-HF group with reduction in fibrosis relative to HF-group. The levels of PPARα targeted genes involved in fatty acid metabolism were significantly increased and BNP was significantly reduced in the WY-HF group in comparison with the HF group. Myocardial high energy phosphates i.e., ATP measured by HPLC were significantly preserved in the WY-HF group.Conclusions: These data suggest that activation of PPARα during heart failure improved myocardial function and energetics. Modulation of FAO will be a new therapeutic strategy for heart failure. P-004 RyR2 Stabilization by Inhibition of CaMKIIMediated Aberrant Ca2+ Release Suppress Arrhythmogenesis in Cardiac Troponin T-Related Hypertrophic Cardiomyopathy Shinichi OKUDA、Masakazu FUKUDA、Takayoshi KATO、 Tetsuro ODA、Shigeki KOBAYASHI、Takeshi YAMAMOTO、 Masafumi YANO Department of Medicine and Clinical Science, Division of Cardiology, YamaguchiUniversityGraduateSchoolofMedicine,Japan Cardiac troponin T(cTnT)mutations that increase myofilament Ca2+ sensitivity cause Familial Hypertrophic Cardiomyopathy(FHC), which leads to sudden cardiac death. However, the underlying mechanism by which the cTnT mutations lead to lethal arrhythmia remains elusive. Here, we investigated the pathogenic role of phosphorylation-mediated aberrant Ca2+ release via cardiac ryanodine receptor(RyR2)and therapeutic effects of dantrolene, which was found to correct inter-domain interactions of RyR2, in transgenic mouse(TG)model with FHCrelated cTnT mutation(TNT-delta160E). In 6-months-old´s TG, there was no appreciable difference in the structural features of hearts, compared with non-TG. In response to isoproterenol(ISO; 10nmol/L), the Ca2+ spark frequency(SpF:s-1m1 )was much higher in TG cardiomyocytes(ISO-TG: 7.9±0.6; p<0.01)than in nonTG cardiomyocytes(3.6±0.4). It was largely reversed by CaMKII inhibitor {KN93(1μM), 5.0±0.4; p<0.05}, but not by PKA inhibitor{H-89(1μM), 7.6±0.3;n.s.}. ISOTG(but not ISO-treated non-TG)showed spontaneous Ca2+ transient(sCaT)after 5Hz pacing, whereas it was attenuated only by KN-93. Moreover, dantrolene(1 μM)attenuated ISO-induced SpF(5.2±0.3; p<0.05 vs ISO-TG), time from peak to 70% decline of Ca2+ transient and sCaT in TG cardiomyocytes. In FHC-linked cTnT-mutated hearts, aberrant Ca2+ release through defective RyR2 was induced by beta-adrenergic stimulation, and subsequent CaMKII activation. Inhibition of CaMKII-mediated aberrant Ca2+ release by stabilizing RyR2 might be a new therapeutic target for preventing the development of arrhythmias in FHC. プログラム・抄録集 ポスター2(P02)心不全と他臓器連関を考える P-005 Dahl食塩感受性高血圧ラットにおける鉄欠乏は 貧血の原因か? 佐々木 尚子 1)、真鍋 恵理 2)、志方 敏幸 1)、増山 理 2)、 野 健 1) 兵庫医療大学 薬学部 医療薬学科、2)兵庫医科大学循環器内科 1) Altered Hypercapnic Chemosensitivity in Conscious Nephrectomized Rats with Myocardial Infarction Tadakazu HIRAI1)、Satoshi NUMA1)、Takashi OHORI1)、 Shuji JOHO1)、Hidetsugu ASANOI2)、Hiroshi INOUE1) 1) The Second Department of Internal Medicine, University of Toyama, Japan、2)ImizuCityHospital Background: Chronic kidney disease(CKD)is an important risk factor for poor outcomes in patients with heart failure( HF). Although exaggerated sympathetic activation could lead to adverse outcome in cardiorenal syndrome, precise mechanism of enhanced sympathetic activation remains unclear. This study was designed to evaluate circadian variations of hypercapnic chemosensitivity and sympathetic tone in nephrectomized rats with HF. Methods: Rats underwent subtotal nephrectomy and surgically induced myocardial infarction (MI). After acclimatization to a 12h light-dark cycle, blood pressure (BP)and heart rate were continuously recorded in conscious rats with CKD and MI by using radiotelemetry pressure transducer. To evaluate hypercapnic chemosensitivity rats were intermittently exposed to 5-min hypercapnic conditions(13%CO2+20%O2)every one hour. Sympathetic tone was assessed by low-frequency components(0.15-0.79Hz)of diastolic BP variability(LFdp). Results: Serum creatinine was increased in CKD rats than those in Sham rats(1.0± 0.3 mg/dl vs 0.5± 0.1 mg/dl, p < 0.05). A transient increase in LFdp was observed during the awaking period in rats with MI+CKD(n=7)when compared to those in SHAM(n=7) (883 ±165 vs 541±165(SE)mmHg2, p<0.05). In rats with MI and CKD, CO2 chemoreflex gain during the awaking period was more enhanced than those of sham rats(p<0.05). Conclusion: In rats with CKD and HF, transient augmentation of chemoreflex gain during the awakening periods could contribute to enhanced sympathetic tone. P-006 Altered Renal Gene Expression in Mice with Heart Failure Induced by Pressure Overload Kazuhiro SHINDO、Masanori ASAKURA、Kyung-Duk MIN、 Miki IMAZU、Hiroki FUKUDA、Masafumi KITAKAZE C l i n i c a l R e s e a r c h a n d D e v e l o p m e n t , N a t i o n a l C e r e b r a l a n d CardiovascularCenter,Osaka,Japan B A C K G R O U N D C a r d i o - r e n a l i n t e r a c t i o n( C R I )a f f e c t s pathophysiology of heart failure(HF)through various mechanisms. However, the impact of renal gene expression on both acute and chronic HF has not been fully unveiled. AIM We aimed to search the genes responsible for CRI using murine pressure overloaded HF model induced by transverse aortic constriction(TAC). METHODS We created TAC and sham mice and conducted echocardiogram followed by sacrifice at 3 days or 8 weeks after operation. RNA samples were corrected from mid-portion of the kidneys and gene expression levels were analyzed by DNA microarray. Obtained data were further analyzed using Ingenuity Pathway Analysis(IPA). RESULTS We compared TAC mice with shams at 3 days(4 TACs vs 2 shams)or 8 weeks(4 TACs vs 4 shams).From 45101 probe sets on the chip, we identified 64(3 days)and 26(8 weeks)up-regulated probe sets with fold-change >1.5. IPA gave us the information about the location and functions of each molecule and we found that these up-regulated genes included secretory proteins and receptors which might be contributed to organ-organ interaction via circulating blood flow, namely PRLR, ADIPOQ, GREM, IGFBP and PSAP. CONCLUSION We identified up-regulation of several genes cording secretory proteins and receptors in kidneys under HF by comprehensible gene expression analysis. They might contribute to the pathophysiology of HF. P-008 VEGF Signaling of the Diabetic Heart by Endothelin Antagonism: Endothelin-A Antagonism and Endothelin-A/-B Antagonism Yumi MIYAUCHI1)、Jesmin SUBRINA1,3)、Satoshi SAKAI2)、 Nobutake SHIMOJO1,3)、Hidekazu MARUYAMA1,2)、Taizo KIMURA2)、 Yoshihiro SEO2)、Satoshi HOMMA2)、Kazutaka AONUMA2)、Takashi MIYAUCHI1,2) Life Science Center for Tsukuba Advanced Research Alliance, University of Tsukuba、2)Division of Cardiology, University of Tsukuba, Tsukuba, Japan、 3)Division of Emergency Medicine, University of Tsukuba,Tsukuba,Japan 1) To study the differences in effectiveness by two types of endothelin (ET)receptor antagonists(selective ET-A or dual ET-A/B antagonists)on the streptozotocin(STZ)-induced rat diabetic hearts(type I diabetes)at functional and biochemical/molecular levels, citrate saline(vehicle)or STZ were injected to rats. The ET-A/B dual receptor antagonist(SB209670)and the ET-A receptor antagonist(TA-0201)were applied to these rats. One week after injection, animals were separated into those receiving SB209670, TA0201or vehicle by 4-week osmotic mini-pump. The VEGF level and percent fractional shortening in the diabetic heart was significantly decreased than in the non-diabetic heart, whereas SB209670 and TA-0201 treatments greatly and comparably prevented this decrease. SB209670 treatment was more effective in reversing decreased expressions of KDR and phosphorylated AKT, downstreams of VEGF angiogenic signaling, than TA-0201 treatment. (Conclusions and Discussion)The present study showed that TA-0201 or SB209670 improved % fractional shortening and VEGF levels of the diabetic hearts in a similar extent, suggesting that ET-A blockade and dual ETA/-B blockade are similarly effective in improving cardiac dysfunction of the diabetic rats. In addition to this finding, the data of improvement in KDR mRNA and pAKT levels by SB209670, but not TA-0201, also suggests that dual ET-A/-B blockade may be effective in improving intracellular signaling systems by these components in the diabetic(type I)rat heart. 259 一般演題 ︵ポスター︶ 【目的】慢性心不全患者の貧血には鉄欠乏が合併するが、それ が貧血の原因かどうかは不明である。慢性心不全のモデル動 物である Dahl 食塩感受性高血圧(DS)ラットは鉄欠乏を伴う 正球性正色素性貧血を発症する。我々は DS ラットの貧血が 鉄補充で改善するかどうかを検討した。【方法】雄性 DS ラッ トをコントロール群(con 群)、高食塩食群(HS 群)、高食塩 食+鉄静注群(HS+Fe 群)の 3 群に分けた。HS 群、HS+Fe 群 には 6 週より 8%NaCl 食を負荷し、貧血が出現し始める 10 週 齢から、HS+Fe 群には含糖酸化鉄注射液 0.2mL (鉄 4mg に相 当)を、HS 群には生理的食塩水を週 1 回尾静脈から注射した。 14 週齢にてサンプリングを行った。【結果】血圧、左心室重量、 血清クレアチニン値は HS 群において上昇し、体重、ヘモグ ロビン値、血清鉄は減少した。これらの指標の鉄補充による 改善は見られなかった。脾臓において、HS 群では貯蔵鉄が 枯渇しており鉄剤静注により con 群と同等に回復しても血清 鉄は上昇しなかった。【結論】DS ラットの貧血に対して、静 注による鉄補充は無効であり、鉄欠乏は貧血の主な原因では なく、鉄の利用障害が存在していることが示された。 P-007 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 ポスター3(P03)心不全の基礎研究における話題 P-009 P-010 Survivin Mediates Protective Effect of Insulin Against Doxorubicin-Induced Cardiotoxicity Via Akt/mTOR/p70S6K/sp1 Pathway Role of O-linked N-acetyl Glucosamine Posttranslational Modification in Intermittent Hypoxia-Induced Cardiac Remodeling Beom Seob LEE1,3)、Jaewon OH2,3)、Seok-Min KANG2,3) Mizuho SASAKI1)、Takatoshi NAKAGAWA2)、Atsuo NOMURA1)、 Ryuji KATO1)、Yoshio IJIRI1)、Takehiro YAMAGUCHI3)、Yasukatsu IZUMI4)、 Minoru YOSHIYAMA3)、Michio ASAHI2)、Tetsuya HAYASHI1) 1) GraduatePrograminScienceforAging,YonseiUniversity、2)Cardiology Division, Yonsei University College of Medicine、 3)Cardiovascular ResearchInstitute,SeveranceCadiovascularHospital,Seoul,Republicof Korea 一般演題 ︵ポスター︶ Background and Objective: Insulin inhibits ischemia-reperfused induced myocardial apoptosis through the PI3K/Akt/mTOR/survivin pathway. Survivin has an anti-apoptotic effect against Doxorubicin(DOX)induced cardiotoxicity. However, whether survivin mediates the protective effect of insulin against DOX injury remains undetermined. This study is aimed to investigate whether survivin plays a role in the anti-apoptotic effect of insulin against the DOX injury in the cardiomyocytes and further to determine the signaling mechanism involved. Methods and Results: We observed that insulin had anti-apoptotic effect against DOX injury by demonstrating reduced caspase-3 activity(from 4.1± 0.3 to 2.8±0.3, p<0.05)and apoptosis index(from 4.1±0.04 to 1.9±0.03, p<0.05), concomitantly increased cell viability( 55.2±7.6% vs. 84.5±0.8%, p<0.05). Transcript and protein levels of survivin were significantly reduced by DOX, which were recovered by insulin through the activation of Akt/mTOR/p70s6k and protein level of Sp1. Pretreatment with rapamycin, a specific mTOR inhibitor or p70s6k inhibitor blocked insulin-induced recovery of sp1 protein expression level against DOX injury. To further ascertain the role of survivin in insulin-induced protective effect, cardiac myocytes were transfected with siRNA of sp1 or survivin. The Sp1 or survivin siRNA significantly blunted the anti-apoptotic effect of insulin against the DOX injury. Conclusions: Our results suggest that survivin mediates protective effect of insulin against DOX-induced cardiotoxicity via Akt/mTOR/p70S6K/Sp1 pathway. LaboratoryofCardiovascularPharmacotherapyandToxicology,Osaka University of Pharmaceutical Sciences, Takatsuki, Japan、2)Department of Pharmacology and Osaka Medical College,Takatsuki, Japan、 3) DepartmentofCardiovascularMedicine,OsakaCityUniversityGraduate School of Medicine, Osaka, Japan、 4)Department of Pharmacology, OsakaCityUniversityGraduateSchoolofMedicine,Osaka,Japan 1) Background: Intermittent hypoxia, a major phenomenon in the sleep apnea syndrome (SAS), is relevant to cardiovascular events, especially in patients with diabetes mellitus (DM). The aim of this study was to evaluate the role of O-Linked N-Acetyl Glucosamine (O-GlcNAc)posttranslational modification in cardiomyocytes exposed to intermittent hypoxia, using DM and O-N-acetylglucosamine transferase transgenic(OGT-Tg)mice. Methods: Male db/db, OGT-Tg, and wild type mice were exposed to intermittent hypoxia (IH; 1 minute of 5% oxygen followed by 5 minutes of 21% oxygen)for 14 days. HEK (Human Embryonic Kidney)293 cells were kept under sustained hypoxia(3-4 %)for 4, 24, 48 hours. Heart was excised and O-GlcNAc modified proteins, OGT, microtubuleassociated protein 1 light chain 3(LC3)were detected by Western blotting.Results: Although fibroblast proliferation in HEK cells under hypoxia was suppressed by O-GlcNAc, IH increased myocardial degeneration and interstitial fibrosis in DM mice, associated with significant increase of O-GlcNAc modified proteins. On the other hand, the LC3-II/LC3-I ratio was significantly increased by IH in OGT-Tg mice, and cardiomyocyte hypertrophy, mitochondrial destruction, and autophagosomes were observed.Conclusion: IH significantly increased oxidative stress and histological degeneration, especially in DM mice with increased O-GlcNAcylation. On the contrary, OGT-Tg mice showed acceleration of autophagy and IH-induced cardiac remodeling. Thus, O-GlcNAc might play a crucial role in cardiac remodeling caused by intermittent hypoxia. P-011 In Failing Cardiomyocytes, Calmodulin Dissociation from Ryr2 and Defective Domain Interaction Leads to Channel Destabilization Tetsuro ODA1)、Takeshi YAMAMOTO2)、 Shigehiko NISHIMURA2)、Takayoshi KATO2)、Sinichi OKUDA2)、 Shigeki KOBAYASHI2)、Donald M BERS3)、Masafumi YANO2) 1) Advanced Medical Emergency and Critical Care Center, University of Yamaguchi,Ube,Japan、2)DepartmentofMedicineandClinicalScience, Division of Cardiology, Yamaguchi University Graduate School of Medicine, ube, Japan、 3)Department of Pharmacology, University of CaliforniaDavis,DavisCA,USA Calmodulin(CaM)binding to RyR2 inhibits diastolic channel activity, indicating that CaM stabilizes the RyR2. In conditions where CaM dissociates from RyR2, like heart failure(HF), RyR2 exhibits destabilized gating and increased activity. Those characteristics make CaM a critical regulator of RyR2 and potential therapeutic target for HF. Another leading mechanism for the RyR2 dysfunction in HF is defective domain interaction between N-terminal and central domains. However, the relationship between CaM-RyR2 binding and defective domain interaction in HF is unclear, especially in cardiomyocytes. Here, in cardiomyocytes from HF rat, we use FRET between fluorescent FKBP12.6 and CaM to detect RyR2-bound CaM and measure the RyR2-CaM binding affinity. The Kd for CaM-RyR2 binding in HF myocytes is ∼ 3 fold increased vs. normal myocytes. By measuring the binding kinetics of fluorescent domain peptide DPc10(F-DPc10), we can detect defective interaction between N-terminal and central domains in myocytes. In HF myocytes, the F-DPc10-RyR2 association rate was significantly accelerated vs. normal myocytes, indicating a destabilized domain interaction(unzipping).However, in HF myocytes, saturating RyR2 with high [CaM] dramatically reduced F-DPc10 binding to RyR2 and greatly slowed the association rate. We conclude that in HF myocytes, reduced CaM-RyR2 binding affinity leads to defective domain interaction, shifting the channel to an "unzipped" state. Promoting CaM-RyR2 reassociation can restore the defective domain interaction and stabilize the channel. 260 プログラム・抄録集 ポスター4(P04)心不全の慢性期管理をどうする P-012 Newly Identification of Antibodies Against Severe Heart Failure Patients Takaharu HAYASHI1)、Yoshihiro ASANO1)、Yasushi SAKATA1)、 Seiji TAKASHIMA2) TheDepartmentofCardiology,UniversityofOsaka,Osaka,Japan、2)The DepartmentofMedicalBiochemistry,UniversityofOsaka,Osaka,Japan、 3) Clinical Research and Development, National Cerebral and CardiovascularCenterResearchInstitute,Osaka,Japan 1) P-013 心不全を発症した壮年期独居者における生活支援 稲谷 怜、松村 さゆり 厚生連 滑川病院 看護部 【背景目的】近年、壮年期における心不全予備軍が増加して おり、早期からの生活指導・是正が重要である。今回、家 族・社会的支援が困難であった壮年期の患者に看護介入した 事例を報告する。【症例】K 氏、40 代男性、心不全で入院。無 職、独居。母・妹との交流はない。【経過】入院 2 ヶ月前に胸 痛出現する。全身浮腫がみられ入院 1 週間前から座位で過ご す。入院前日に自殺企図し入院となる。入院時 NYHA IV 度、 BNP 6751 pg/ml、両下肢、腹部より浸出液がみられた。入院 時より病態説明や生活指導、入院前の生活について看護師と 面談し、振り返りを行う。経済的問題は多職種と協働し話し 合いの上退院となる。 【考察】今回の事例では K 氏が独居、家 族と疎遠状態であるため、今後の生活や、K 氏のセルフモニ タリング能力が問題となった。K 氏は入院前の下肢浮腫・浸 出液を 「汗」 と捉えるなど、セルフモニタリングにおける知識・ 技術・関心が低いといえたが、心不全症状が軽減していく過 程で症状や状態・治療に合わせ、生活指導を受けたことで、 身体への興味・関心が高まったと思われる。 P-015 The Effect of Left Ventricular Hypertrophy and Associated Diastolic Dysfunction on Left Ventricular Remodeling and Exercise Capacity in a Murine Model of Mitral Regurgitation 再入院を繰り返す肺気腫合併肺線維症を併せ持っ た慢性心不全患者への継続看護と地域連携に対す る一考 Kyung-Hee KIM1)、Yong-Jin KIM2)、Seung-Pyo LEE2)、 Hyung-Kwan KIM2)、Dae-Won SOHN2) 岩尾 雅子 DivisionofCardiology,DepartmentofInternalMedicine,SejongGeneral Hospital & Sejong Heart Institute、2)Department of Internal Medicine, Cardiovascular Center, Seoul National University College of Medicine, SeoulNationalUniversityHospitalSeoul,Korea 高齢化が急速に進み家族の在りようも変化する中、地域包括 ケアの構築が重要視されている。看護の対象が変化する中に おいて、患者と医療者の問題認識の相違が退院後の生活に支 障をきたした慢性心不全に肺気腫合併肺線維症を併せ持つ患 者の退院調整に関わる機会を得たので報告する。看護師は問 題を妻と死別し独居生活、活動制限の必要はあるが生活維持 のために動かざるを得ない状況である事、労作性呼吸困難に より退職し生活保護、介護申請適応年齢外、経済力介護力と もに不足している事と捉えていた。患者は、心筋 塞は完治 し呼吸器疾患は継続との認識で退院したが、再入院後は今 通りの生活が難しいと考えるようになった。同時に社会的な 援助を希望され、 退院前カンファレンスにてケアマネージャー と身体精神的状況と問題点を共有することで、掃除や買い物 などヘルパーを週 3 回、疾病管理や精神的支援のため訪問看 護を週 2 回配置する計画が立案された。家庭復帰初期の再入 院しやすい時期に在宅支援者のケアマネージャーや訪問看護 師と地域連携し外的統制を行うことが再入院の延長に繋がっ たと考える。 1) Introduction: Degenerative mitral regurgitation(MR)is often accompanied by left ventricular hypertrophy(LVH)and diastolic dysfunction. Objectives: This study determined the contribution of LVH and associated diastolic dysfunction on LV remodeling and exercise capacity in rats with significant MR. Method: LVH and diastolic dysfunction were created by suprarenal aortic constriction(SAC)in SD rats. Serial echocardiographic studies and exercise were performed at 2-week intervals and invasive hemodynamic examination by a pressure-volume catheter system was done at 14 weeks after SAC. To test the effect of LVH and diastolic dysfunction on LV remodeling and exercise capacity, the rats were divided into 3 groups [SAC+MR =SAC followed by MR operation, MR=laparotomy followed by MR operation, Control]. MR was created by introducing a needle through LV apex under the guidance of TEE and making a hole on anterior mitral leaflet. MR was considered significant if a regurgitant jet area occupied more than 45% of the left atrium. SAC was done at 2 weeks before MR formation in SAC+MR group. Results: During the LVH and diastolic dysfunction experiment, LV wall thickness increased in LVH group compared to control group whereas LV ejection fraction(EF)and E/E' did not change. In hemodynamic analysis, LV end diastolic pressure and the EDPVR slope were greater in LVH group than in control group. Next, when we compared LV remodeling and exercise capacity between above 3 groups, LV dilatation and exercise intolerance were developed first in SAC+MR group. However, MR group showed a catch-up of remodeling and exercise intolerance at 10 weeks after MR formation(LV ESD at 10 weeks after MR formation, 4.33±0.26 vs. 6.50±0.40 vs. 6.59±1.38 mm for control vs. MR vs. SAC+MR, P<0.05; LV EDD, 7.68±0.15 vs. 10.48±0.46 vs. 10.20±1.26 mm, P<0.05; exercise duration, 765.3±130.1 vs. 487.8± 49.0 vs. 434.0±80.3 seconds, P<0.05; no statistical differences between SAC+MR and MR). In neurohormonal activity, the level of BNP was not different between 3 groups. However interstitial fibrosis is greater in SAC+MR compared with MR and control. Conclusion: We successfully set up two small animal models of LVH accompanied with diastolic dysfunction and significant MR. LVH and associated diastolic dysfunction did not affect LV remodeling and exercise capacity over time in rats with significant MR. 獨協医科大学越谷病院 261 一般演題 ︵ポスター︶ <Background>The ventricular assist device(VAD)is poweful in the course of the treatment for heart transplantation. But it is difficult to decide when to perform VAD implantation. Sometimes biopsy samples of heart tissue from severe heart failure patients revealed the inavasion of many lymphocytes, despite the absence of myocarditis.<Purpose>We hypothesized there might be concerned with autoimmune responce, therefore evaluated relationship between autoimmunity and severe heart hailure.<Methods and Results>We collected blood serum from 37 heart failure patients and 10 VAD patients along with 100 healthy normal subjects. Using homogenated normal human heart lysate, we performed western blot analysis by their serum. We could find several specific auto-antigens and to identify the protein, we next made purification of these proteins by an anion exchange and reverse phase HPLC. We finally identified 4 proteins as auto-antigen candidates by MS analysis. For example, one out of antigen X were detected against the serum from 4 out of 10 VAD implantation patients, which could find only one out of a hundred healthy normal subjects(P<0.01).<Conclusion> In this study, we identified specific auto-antigens in severe heart failuer patients. It will be a marker of severe heart failure and useful for us to decide VAD implantation. P-014 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 P-016 P-018 心不全患者に関する生活指導プロトコールを作成して 心不全患者のセルフモニタリングに関する現状 小林 希望、原田 友香、前田 京子 竹之内 恵、肥後 あかね、木本 直子、田上 さとみ 特定医療法人明石医療センター 独立行政法人国立病院機構鹿児島医療センター 一般演題 ︵ポスター︶ 【目的】平成 24 年に、セルフケア能力を査定する質問紙(SelfCare Agency Questionnaire, 以下、SCAQ)を用いて心不全患 者の弱みを抽出し生活指導を行った結果、セルフケア能力の 向上を認めた。しかし、SCAQ の活用には時間を要し、研究 メンバーのみが情報整理を行った。そのため、他スタッフは SCAQ の使用方法を理解出来ておらず、活用できていない。 そこで、心不全患者の弱みへの支援を、病棟全体で行えるよ うにすることを目的とした。【方法】SCAQ の活用とカンファ レンスを含めた、指導プロトコールの作成を行った。 プ ロトコールは、カンファレンスと実践を繰り返し作成し、患 者・看護師ともにわかりやすくした。 【結果と結語】スタッフ が指導を行った結果、8 人の初回心不全患者の SCAQ 値は、 Wilcoxon の符号順位和検定、X2 による分析で、指導前より 有意な向上を認めた。カンファレンスも開催でき、個別性に 応じた指導へとつながったと考える。また、初回入院でない 慢性心不全患者はすでに自己管理法を持っていることが多く、 今回のプロトコールを用いた指導は不向きであることもわ かった。 目的 心不全患者の入院時・退院後のセルフモニタリングの状況を 把握し、現在の療養生活指導の効果を明らかにする。 結果および考察 心不全の診断で入院となった患者を対象に心不全患者のセル フモニタリング評価尺度を使用し調査を行った。入院 1 週間 以内のセルフモニタリングの状況について初回入院患者と再 入院患者を比較した結果、「水分貯留に対する解釈」のみ有意 差を認めた。パンフレットを使用した一般的な指導では、患 者が自らセルフモニタリングを行えるような行動変容に繋が らなかったと考えられる。また追跡調査を行い、入院 1 週間 以内と退院 1 ヶ月後のセルフモニタリングの状況について比 較した結果、「体調を定期的に測っている」「測定結果が気に なる」 「水分の量を気にしている」 「動きに伴う身体の調子を 気にしている」 「体調管理の状況と症状に対する解釈」 「脈の 悪化に対する解釈」「水分貯留に対する解釈」について有意差 を認めた。現在の療養指導では 「自覚」 「測定」 について効果が あるが、「解釈」については効果が乏しく、どのように 「解釈」 しているか具体的に確認を行うことが心不全患者の療養生活 指導において重要であることが明らかとなった。 P-017 P-019 高度血圧上昇による急性心不全例の特徴と生活支 援の必要性についての検討 心不全多職種チームと在宅部門との協働で目指す 包括的疾病管理についての一考察 白倉 透規 1)、布施 公一 2)、相澤 義房 3) 平野 美樹 1)、佐々木 真弓 1)、飯塚 裕美 1)、末永 祐哉 2)、鈴木 誠 2) 立川メディカルセンター 立川綜合病院 看護部、 立川メディカルセン ター 立川綜合病院 循環器内科、3)立川メディカルセンター 研究開発部 1) 2) 【背景と目的】疫学調査からみた急性心不全の背景に高血圧が 大きく関わっており、高血圧を基礎疾患とする例が 50-70%、 急性心不全の直接の原因となる例が 20% 前後とされる。血圧 上昇が誘因として発症する中には、高度血圧上昇をきたす例 がある。そのような症例の患者背景と生活支援方法について 検討する。【対象と方法】2011 年 4 月 1 日∼ 2014 年 3 月 31 日に 収縮期血圧が 190mmHg 以上を呈して入院となった急性心不 全症例を対象に、臨床像、入院前の生活背景を分析した。 【成 績】年齢は平均79.5歳で、血圧は平均213/101 mmHg であった。 いずれも血圧の急激な上昇を機に緊急入院となったもので全 例初回入院であった。基礎疾患に高血圧を 14 例で認め、血圧 上昇の原因として服薬管理・塩分水分管理・セルフモニタリ ングの不足があった。入院前に心不全症状が認められており、 処置の遅れも指摘できた。【考察】症例は殆どが高齢者であり、 治療アドヒアランスやセルフケアが低いため、高度な血圧上 昇による急性心不全をきたしたと考えられた。外来での多職 種支援体制構築と入院中の継続した支援が再発予防に重要と 考えられた。 262 亀田総合病院看護部、2)亀田総合病院循環器内科 1) 【背景】心不全増悪に伴う再入院を回避するためには、多職種 による包括的な疾病管理が効果的であると報告されている。 当院も多職種チームで疾病管理における包括的介入を開始し たが施設完結型で、 再入院を防ぐためには在宅とのネットワー ク構築の必要性が求められていた。【目的】多職種による包括 的疾病管理に訪問看護の積極的導入を試みることで、再入 院率の減少につなげられるか検討する。【方法】2013 年 3 月∼ 2014 年 2 月までに入院した心不全患者 279 名に対して、再入 院のリスクが高いと判断した患者に訪問看護の導入を検討し た。【結果】14 名が高リスクと判断され 2 名は拒否し 12 名に訪 問看護を導入。患者の転帰は 12 名中、再入院 6 名、死亡 1 名で、 導入者の生活背景は 12 名中、独居 3 名、高齢者世帯 4 名、そ の他 5 名であった。【考察】訪問看護師が加わり在宅療養への 円滑な移行が実現し、再入院を繰り返していた患者において、 心不全増悪を回避することができた。再入院に至った症例も、 入院中から退院後の患者情報を共有でき、薬剤調整や早期外 来受診の調整等、重症化する前に入院となった。今後は、近 隣の地域とも連携を図り、地域完結型の疾病管理へと発展さ せていきたい。 プログラム・抄録集 ポスター5(P05)栄養・生活習慣と心不全 P-020 Relationships Between Nutritional Status and Markers of Congestion in Patients with Pulmonary Arterial Hypertension Akira KAWAMOTO1,3)、Takao KATO2)、Yoshiaki OKANO3)、 Tetsuo SHIOI3)、Takeshi KIMURA3) Hamamatsu Rosai Hospital、 2)Cardiovascular Center, the Tazuke Kofukai Medical Research Institute, Kitano Hospital、3)Department of CardiovascularMedicine,GraduateSchoolofMedicine,KyotoUniversity 1) P-021 The Fischer Ratio in Patients with Chronic Heart Failure Shuhei TSUJI、Yukihito SATOU HyogoPrefectualAmagasakiHospital,Hyogo,Japan Background: Cachexia is a common complication in severe chronic heart failure(HF). Patients with HF complicated with cachexia showed increased mortality, but its pathophysiology is not fully understood. Hence, this study aimed at identifying malnutrition in HF patients from the viewpoint of amino acid concentration.Methods: To clarify the relationship between amino acids and HF, we collected blood samples from 113 HF patients(male, 61(54%); mean age, 73.9±8.8 years; mean ejection fraction, 53±16%; median serum B-type natriuretic peptide( BNP)concentration, 2 2 9 . 6 p g / m l ), a n d m e a s u r e d t h e s e r u m a m i n o a c i d composition.Result: The median Fischer ratio(the molar ratio of branched chain amino acids to aromatic amino acids)was 2.7. Patients with higher Fischer ratio were younger (P<0.001), and had higher body mass index(P<0.001), hemoglobin(P<0.001),and albumin(P<0.001),and lower high density lipoprotein(HDL)cholesterol(P=0.003), and BNP (P<0.001). In the multivariable analysis, the Fischer ratio was positively correlated with albumin(correlation coefficient (CC)=0.489; 95% confidence interval(CI), 0.183 ∼ 0.795; P=0.002), and negatively correlated with HDL cholesterol (CC=-0.025; 95% CI, -0.008 ∼ -0.025; P<0.001), and BNP(CC=0.695; 95% CI, -1.111 ∼ -0.277; P=0.001).Conclusion: In the patients with HF, the Fischer ratio was paralleled with poor control of HF represented as a high BNP concentration. Thus, HF patients may have poor nutritional status. P-023 Changes of Metabolomic Profiling are Associated with Reduced Exercise Capacity in Patients with Heart Failure Prognostic Impact of Preexisting Hypertension in Hospitalized Patient with Established Systolic Heart Failure Masaya TSUDA、Shintaro KINUGAWA、Arata FUKUSHIMA、 Takashi YOKOTA、Shoji MATSUSHIMA、Takaaki FURIHATA、 Shingo TAKADA、Masato KUDO、Junichi MATSUMOTO、Hiroyuki TSUTSUI Byung-Su YOO1)、Seok-Min KANG2)、Eun-Seok JEON3)、 Dong-Ju CHOI4)、Myeong-Chan CHO5)、Kyu-Hyung RYU6) Department of Cardiovascular Medicine, Hokkaido University Graduate SchoolofMedicine,Sapporo,Japan Background: Exercise intolerance is a major clinical manifestation, and closely related to poor prognosis in heart failure(HF)patients. Metabolic derangements have been shown to be involved in this phenomenon. We thus investigated the metabolites associated with exercise capacity by using global metabolomic analysis of plasma samples in HF patients. Methods and Results: Ten consecutive HF patients with reduced ejection fraction(57 ± 12 years, NYHA class II-III)and 5 age-matched healthy subjects as controls(56 ± 3 years)were studied. Charged metabolites in plasma samples were measured by capillary electrophoresis mass spectrometry. Peak oxygen uptake (peak VO2), anaerobic threshold(AT), and VE/VCO2 slope were measured by cardiopulmonary exercise test. A total of 233 charged metabolites were identified. Significant increases in arginine methylation, phospholipid metabolites, and urea cycle metabolites were observed in HF patients compared to controls. Methylarginine including asymmetric dimethylarginine( ADMA)(r=-0.77, P<0.001)and symmetric dimethylarginine(SDMA)(r=-0.65, P=0.040)levels, and phospholipid metabolites including choline( r=-0.63, P=0.049)and N,N dimethylglycine(r=-0.75, P=0.011)levels were negatively correlated to both peak VO2 and AT in HF patients. N,N -dimethylglycine(r=0.72, P=0.026)and Urea (r=0.82, P=0.006)levels were positively correlated to VE/VCO2 slope. Conclusions: Increases in metabolites of arginine methylation, phospholipid metabolism, and urea cycle are associated with exercise intolerance in HF. These results provide mechanistic insights into exercise intolerance associated with HF. 1) Division of Cardiology, Wonju College of Medicine, Yonsei University, Wonju, Korea、2)Division of Cardiology, Yonsei University Severance Hospital, Seoul, Korea、 3) Division of Cardiology, Sungkyunkwan University Samsung Medical Center, Seoul, Korea、 4) Division of Cardiology, Seoul National University Bundang Hospital, Seongnam, Korea、5)Chungbuk National University College of Medicine, Cheongju, Korea、6)DivisionofCardiology,HallymUniversityMedicalCenter,Korea Background: Hypertension is the most common risk factor and co-morbidity for heart failure. However the prognostic value of the hypertension in established heart failure has not been well evaluated. The aim of present study was to investigate the prognostic impact of preexisting hypertension in patients hospitalized with systolic heart failure. Method: We performed a pooled analysis of data from three multi-center, observational studies [KorHF, the Korean Heart Failure Registry; SUGAR, SUrvey of Guideline Adherence for Treatment of Systolic Heart Failure in Real World; COAST, Clinical Outcomes in Relation with Serum Sodium Level in Asian Patients Hospitalized for Systolic Heart Failure] across Korea. We selected the patients with systolic heart failure(Ejection fraction(EF)<45%)and > 18 years old. Then we divided the subjects into 2 groups by presence of preexisting hypertension history: Hypertension group and No hypertension group. Study endpoints included all cause mortality and rehospitalization within 1 year. Results: Total 3877 patients were enrolled. Mean EF was 29.6 ± 8.7 %. The prevalence of preexisting hypertension was 51.5%. Patients with hypertension presented more often diabetes(44.4% vs. 23.3%, P<0.001),previous MI(15.5% vs. 12.2%, p<0.001), Stroke(16.3% vs.8.4%, p<0.001)and chronic kidney disease(14.7% vs. 6.1%, p<0.001). At 1 year followup, patient with hypertension had a higher rehospitalization rate(31.5 % vs. 26.6%, p=0.001)but, mortality rate was not significant difference between 2 groups(14.1% vs. 14.7%, p=0.624). After adjusting for baseline clinical variables(age, sex, diabetes, prior MI, atrial fibrillation, ejection fraction, LBBB, serum creatinine etc), the presence of hypertension was independently associated with lower 1 year mortality rate(OR 0.73 95% CI 0.548 - 0.966)and higher prescription of medications(ACE inhibitor or ARB OR 1.389 95%CI 1.118 - 1.724, beta blocker OR 1.517 95% CI 1.260 - 1.827). Conclusions: Preexisting hypertension was independently associated with lower 1 year mortality rates and higher prescription of medications in systolic heart failure. 263 一般演題 ︵ポスター︶ Purpose: Right ventricular(RV)dysfunction and cachexia often coexist; however, there are few studies investigating pulmonary arterial hypertension(PAH)and nutritional status. This study sought to examine the relationships among nutritional status, markers of congestion, and echocardiographic parameters in patients with stable PAH.Methods: In this prospective study, subjects with stable PAH(n=8)underwent the subjective global assessment(SGA)for nutritional status, blood tests, and comprehensive echocardiography. Results: Estimated systolic pulmonary artery pressure(ePAP)and BNP levels were 82.7±15.7(mean ±SD)mmHg and 176±146 ng/L, respectively. Left ventricular diastolic diameter(LVDd)was negatively correlated with ePAP(r=-0.70, p=0.04), implying a dilated RV and compressed left ventricle(LV). Blood urea nitrogen, a marker of protein catabolism, was positively correlated with SGA scores(r=0.81, p<0.01)and BNP(r=0.68, p=0.04)and negatively with LV diameter(r=-0.87, p<0.01).Serum pre-albumin, a rapid turnover hepatic protein, was positively correlated with ePAP(r=0.70, p=0.01)and negatively with serum sodium concentrations( r=-0.56, p=0.02). In multiple regression analyses, BMI was determined by WBC count, ePAP, serum sodium and AST concentrations, and IVC diameter.Conclusion: There were strong correlations between markers of nutritional status, markers of congestion, and PAH severity. These results suggest that poor nutritional status and cachexia may be surrogate markers for PAH severity and potential therapeutic targets for PAH. P-022 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 ポスター6(P06)心不全と腎機能の連関 P-024 A Case of Using Pedometer for Severe Heart Failure Patients Daiki GYOTOKU、Yuka KUSAKAWA、Hidekuni KIRIGAYA、 Nao YAMADA、Naoki IINUMA、Yuko MIKI、Tastuya NAKACHI、 Kazuki FUKUI Cardiology,KanagawaCardiovascularandRespiratoryCenter 一般演題 ︵ポスター︶ W e r e p o r t a c a s e t h a t t h e p e d o m e t e r( L i f e c o r d e r PLUS;SUZUKEN)was effective for prevention of heart failure exacerbation. A 80-year-old man with a chronic heart failure due to ischemic cardiomyopathy hospitalized 30 times. He had anterior myocardial infarction in 2005, and performed percutaneous coronay intervention in our hospital. Echocardiography showed LVEF was 30%, and a cavity of left ventricular was extremely dilated. We treated him with fully optimized medication, and introduced adaptive serve ventilations(ASV).However, he was hospitalized 3-4 times/ year due to acute heart failure. Since Nov 2013, he was hospitalized every month. Frequency of the hospitalization increased. We suspected that hyperactivity participated in heart failure aggravation, we started to grasp of his daily steps using pedometer. It started from Apr 2014, and period of observation was 4 weeks. Average steps was 801 steps/ day(max 1803 steps/day, min 146 steps/day). His condition was stable after introduction with a pedometer. In this case, low physical activity contribute to prevent heart failure exacerbation. P-026 Acute Kidney Injury Predicts Heart Failure and Mortality in Patients with ST-segment Elevation Acute Coronary Syndrome Shinichi OKINO、Atsushi IKEDA、Shigeru FUKUZAWA、 Masayuki INAGAKI DivisionofCardiology,HeartandVascularInstitute,FunabashiMunicipal MedicalCenter Aim The aim of this study is to investigate the impact of acute kidney injury(AKI)on prognosis in patients with STsegment elevation acute coronary syndrome (STE-ACS). Methods The population consisted of 423 STE-ACS patients undergoing primary PCI. AKI was defined as an increase in serum creatinine level of 0.3 mg/dL or more from baseline within 48 hours. Mean follow-up period was 33.7±18.9 months. Clinical event (CE) was defined as re-admission due to heart failure or death. Results There were 78 AKI patients. AKI had more chronic kidney disease( CKD)and cardiogenic shock. AKI patients had higher incidence of CE than non-AKI patients regardless of CKD. Multivaritate analysis showed AKI, maximum CK-MB and cardiogenic shock were independent predictors of CE. Conclusion AKI was a predictor of CE. P-025 P-027 Is There a Gender Difference of Obesity Paradox in Systolic Heart Failure? Gender Difference of Obesity Paradox. Clinical Response of Tolvaptan in Patients with Heart Failure Who Had End-Stage Renal Function Byung-Su YOO1)、Seok-Min KANG2)、Eun-Seok JEON3)、 Dong-Ju CHOI4)、Myeong-Chan CHO5)、Sang Hong BAEK6)、 Shung Chull CHAE7)、Hyun-Young PARK8)、Byung-Hee OH9) Shinsuke HARASAWA1)、Kiyoshi IIDA1)、Tadashi ASHIDA1)、Daisuke KISO1)、 Masakazu MATSUZAKI1)、Takehiko WASHIO1)、Katsuaki OOKUBO1)、 Hirofumi KAWAMATA1)、Naoya MATSUMOTO1)、Atsushi HIRAYAMA2) 1) Division of Cardiology, Wonju College of Medicine, Yonsei University, Wonju, Korea、2)Division of Cardiology, Yonsei University Severance Hospital, Seoul, Korea、 3) Division of Cardiology, Sungkyunkwan University Samsung Medical Center, Seoul, Korea、 4) Division of Cardiology, Seoul National University Bundang Hospital, Seongnam, Korea、5)Chungbuk National University College of Medicine, Cheongju, Korea、6)The Catholic University of Korea, Seoul, Korea、7)Kyungpook National University College of Medicine, Daegu, Korea、 8)National Institute of Health (NIH), Osong, Korea、 9)Department of Internal Medicine,SeoulNationalUniversityHospital,Seoul,Korea 1) Purpose: The aim of the present study was to investigate the prognostic value of the obesity in patients hospitalized with acute heart failure syndrome. Method: The Korean acute heart failure registry(KorAHF)is an on-going prospective multicenter cohort study for acute HF. As of November 2013, interim analysis of 4184 patients was performed. We categorized the study population into 4 groups by BMI value(kg/m2); BMI<18.5, 18.5 BMI<25, 25 BMI<30 and 30 BMI. Study endpoint included all cause death and rehospitalization. Results: Of total 3618 patients, 549(28.3%)and 489(29.1%)reached study endpoints in men and women, respectively. After adjusting, the male patients with BMI 30 showed the lowest risk(Hazard ratio [HR]: 0.472, 95% CI: 0.267-0.836, p=0.010)compared to those with BMI<18.5. This correlation between BMI and study endpoint was not remarkable in women. In male, patients with HF with reduced ejection fraction(EF<40%),patients with BMI 30 showed the lowest risk(HR: 0.323, 95% CI: 0.138-0.755, p=0.009)for study endpoint compared to those with BMI<18.5. However this correlation was not noted in patients with preserved ejection fraction in male. Conclusions: In KorAHF registry, there was a gender difference of obesity paradox in patients with AHF. BMI was the independent risk factor for adverse cardiac events in men who have HF with reduced ejection fraction. 264 DepartmentofCardiology,NihonUniversitySurugadaiHospital,Tokyo, Japan、 2) Division of Cardiology, Department of Medicine, Nihon UniversitySchoolofMedicine,Tokyo,Japan Background: A newly-developed vasopressin-2 receptor antagonist, Tolvaptan(TLV), has been shown to improve volume overload through free water excretion, however, the effect of TLV on renal function is still unclear. Purpose and methods: This study aimed to investigate whether TLV has a clinical efficacy in patients with heart failure who had renal dysfunction. We classified 67 patients who received TLV according to the renal function and examined the response of TLV using urine volume as well as short-term prognosis. Results: Urine volume increase with dose dependence fashion was observed in preserved eGFR group(>30), but did not observed in low eGFR group(<30). The higher in baseline serum creatinine level, the more frequent the occurrence of worsening renal function(WRF) (defined by absolute increase >0.3mg/dl in serum creatinine level from baseline to follow up). All-cause mortality and renal death(fall into dialysis)were significantly higher in patients who complicated with WRF as compared without WRF. Efficacy of TLV and short-term prognosis were especially poor in end-stage renal disease patients who had the nephrotic syndrome. Conclusions: The clinical efficacy of TLV in patients with endstage renal disease was modest, and especially in patients with nephrotic syndrome. プログラム・抄録集 P-028 Renal Function Improvement in Chronic Heart Failure is Associated with Less Risk of Pump Failure Death but Not Sudden Death Satoshi TAKAHASHI、Takashi MORITA、Shunsuke TAMAKI、 Masatake FUKUNAMI、Takahisa YAMADA DivisionofCardiology,OsakaGeneralMedicalCenter P-029 Chronic Kidney Disease in Hospitalized Patients with Heart Failure Satoko NAKAMURA1)、Toshihisa ANZAI2)、Yuhei KAWANO1) 1) Division of Hypertension and Nephrology, National Cerebral and Cardiovascular Center, Suita, Japan、2)Department of Cardiovascular Medicine,NationalCerebralandCardiovascularCenter,Suita,Japan Background: Chronic kidney disease(CKD)and cardiovascular diseases( CVD)are related to the development of kidney impairment. However, the prevalence of CKD or kidney impairment and its consequences in hospitalized patients with CVD are not well clarified. Methods: We performed a prospective study, in which 74 consecutive patients with heart failure were enrolled. Blood and urine samples are collected at the time of hospitalization, interventions and discharge. Estimated glomerular filtration rate(eGFR)was calculated from serum creatinine and age using Japanese equation. CKD was defined by eGFR less than 60(ml/min/1.73m2)and/or the presence of proteinuria. Results: Patients were divided into the groups with CKD (n=30, 41%)and without CKD(n=44, 59%). The age was 72 ±10 and 57±15(years old), and eGFR was 42±4 and 79±16 (ml/min/1.73m2), respectively. The presence of traditional CVD risk factors was more evident in the patients with CKD compared to those without CKD. Serum albumin and HDL cholesterol were lower, and uric acid, fasting glucose and BNP were higher in the patients with CKD. eGFR was significantly related to age and several traditional risk factors. Conclusions: In patients with heart failure, kidney function was frequently deteriorated at admission. Aging and traditional CVD risk factors as well as impaired cardiac function may contribute to CKD in heart failure. P-031 The Impact of Kidney Dysfunction on HypoAlbuminemia and Cardiac Prognosis in Patients with Chronic Heart Failure Effectiveness of Carperitide for Preventing Worsening Renal Function(WRF)in Patients with Heart Failure Yoichiro OTAKI、Tetsu WATANABE、Akira FUNAYAMA、 Hiroki TAKAHASHI、Takanori ARIMOTO、Tetsuro SHISHIDO、 Takuya MIYAMOTO、Isao KUBOTA Taro SASAOKA、Mie SEYA、Shunji YOSHIKAWA、 Yasuhiro MAEJIMA、Masahiko GOYA、Takashi ASHIKAGA、 Kenzo HIRAO、Mitsuaki ISOBE YamagataUniversitySchoolofMedicine,Yamagata,Japan Department of Cardiovascular Medicine, Tokyo Medical and Dental University,Tokyo,Japan Background Hypo-albuminemia is closely associated with poor prognosis in patients with chronic heart failure(CHF). Although kidney plays a pivotal role in excretion and reabsorption of albumin and amino acid, it remains to be fully elucidated the impact of kidney dysfunction on hypo-albuminemia in patients with CHF. The aim of the present study was to reveal the impact of kidney dysfunction on hypo-albuminemia and cardiac prognosis in patients with CHF.Methods and Results We included consecutive 296 patients with CHF. Albuminuria and renal tubular damage(RTD)were defined as a urinary albumin to creatinine ratio(UCAR)>30mg/g and urinaryβ2-microglobulin to creatinine ratio (UBCR)>300 μg/g, respectively. There was a modest correlation between kidney dysfunction and serum albumin(UACR, r=0.300, P<0.0001; and UBCR, r=0.434, P<0.0001). Multivariate logistic analysis showed that RTD was significantly related to hypo-albuminemia in patients with CHF after adjustment for confounding factors. During a median period of 1060 days, there were 87 cardiac events. Net reclassification index and C index were significantly improved by addition of RTD to basic risk factors. All patients were divided into 3 groups: hypo-albuminemia+RTD group, hypo-albuminaemia or RTD group, and control group. Kaplan-Meier analysis demonstrated that hypo-albuminemia+RTD group had the greatest risk among 3 groups. Conclusion Kidney dysfunction, in particular RTD, is closely associated with hypo-albuminemia and could identify patients at high risk. Background: WRF is an important matter in heart failure. Some studies have demonstrated Carperitide might have a favorable effect in cardiorenal syndrome; however, the detail of its effect was not fully investigated.Method: A total of 66 non-hemodialysis patients admitted to our hospital for acute decompensated heart failure(ADHF)in 2010 and followed at 1 year were retrospectively reviewed. They were divided in 2 groups according to the Carperitide usage, Carperitide group(n=41), and non-Carperitide group(n=25). WRF was defined as the occurrence of both 25% increase and 0.3 mg/dL increase in serum creatinine levels during hospitalization. Result: Average dose of Carperitide was 0.026γ. Left ventricular function and BNP levels at admission were not different. WRF was significantly lower in Carperitide Group(12/41, 29%)than non-Craperitide group(13/25, 52%, p<0.05). Survical rate at 1 year is tended to be lower in nonCarperitide group(85% vs 68%), but not significantly different. In Carperitide group, estimated glomerular filtration rate(eGFR)levels at admission, discharge, and 1year(45.5, 48.4, and 49.0ml/min/1.73m2, n.s.)were not significantly different. On the other hand, eGFR levels were significantly decreased at 1 year compared with admission in non-Carperitide group(62.7, 52.3, and 37.4 ml/min/1.73m2, p<0.05). Conclusion: In this study, Carperitide was effective to prevent WRF. Also, it had a favorable long-term renal protective effect. 265 一般演題 ︵ポスター︶ To investigate the prognostic significance of the renal function improvement in patients with chronic heart failure (CHF), from a viewpoint of mode of death(sudden cardiac death(SCD)and pump failure death(PFD), we studied 123 CHF outpatients with LVEF<40%. Forty-nine pts had an improvement in eGFR(58±15 to 64±17 ml/min/1.73m2, p<0.01)at 1 year after the entry, while the remaining 74 pts had an eGFR decline( 66±21 to 59±20ml/min/1.73m 2, p<0.01). During a follow-up period of 7.4±4.4 years, PFD was significantly less frequently observed in pts with than without eGFR improvement, while there was no significant difference in SCD incidence between the two groups. Thus, CHF pts with eGFR improvement had less risk for PFD, while they are still at risk of SCD. P-030 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 ポスター7(P07)心不全における様々な薬物療法 P-032 Effects of Intensive Versus Mild Lipid Lowering with Statins in Congestive Heart Failure with Ischemic Origin Hae-Young LEE1)、Hyun-Jai CHO1)、Hee-Yul KIM2)、 Hee-Kyung JEON3)、Joon Han SHIN4)、Suk-Min KANG5)、 Sang Hong BAEK6) Seoul National University Hospital、2)The Catholic University of Korea Bucheon St.Mary’s Hospital、 3)The Catholic University of Korea Uijeongbu St. Mary's Hospital、 4)Ajou University Hospital、 5)Yonsei UniversitySeveranceHospital、6)TheCatholicUniversityofKoreaSeoul St.Mary'sHospital 1) 一般演題 ︵ポスター︶ Background and Aim. As the role of statins in congestive heart failure(CHF)are still unclear, this study was designed to evaluate the dose-effect relationship of statins in ischemic CHF patients. Methods. The South koreAn Pitavastatin Heart FaIluRE Study (SAPHIRE)was designed to randomize ischemic CHF patients in pravastatin 10mg or in pitavastatin 4mg daily group. Results. 1)The LDL cholesterol level was reduced by 30 % significantly greater in the pitavastatin 4mg group compared with 12% in the pravastatin 10 mg group 2)The left ventricular systolic dimensions were significantly reduced by 9% in the pitavastatin group and by 5% in the pravastatin group. The left ventricular ejections were significantly improved from 37% to 42% in the pitavastatin group and from 35% to 39% in the pravastatin group. Although the extent of the EF change was greater in the pitavastatin group(+16% vs + 11%),there was no statistical significance between two groups(p = 0.3862). 3)The exercise capacity evaluated by 6-minute walk test was improved significantly in the pravastatin 10mg group(p = 0.0002), however, there was no changes in the pitavastatin group(p = 0.3707). Conclusions: In CHF patients with ischemic origin, too much lowering of cholesterol might not be beneficial to CHF patients. P-033 Diabetes Mellitus is a Poor Prognostic Risk but Has a Therapeutic Potential for Functional Reversibility in Nonischemic Systolic Heart Failure Yuki IKEDA、Takayuki INOMATA、Teppei FUJITA、Yuichiro IIDA、 Takeru NABETA、Shunsuke ISHII、Takashi NARUKE、 Hisahito SHINAGAWA、Toshimi KOITABASHI、Junya AKO Department of Cardiovascular Medicine, Kitasato University School of Medicine Purpose: To identify the association between diabetes mellitus (DM)and clinical outcome in patients with nonischemic heart failure with reduced ejection fraction(NI-HFrEF). Methods: We evaluated 248 patients with NI-HFrEF at baseline, 6 months, and 1 year, then observed for cardiac events(CEs)such as heart failure worsening or cardiac deaths. Results: Seventy-five(30%)patients had DM. Kaplan-Meier analysis revealed DM was related to higher incidence of CEs(Figure A). However, patients with DM and improved hemoglobin(Hb)A1c during 6 months showed lower incidence of CEs(Figure B), and higher HbA1c at baseline was independently related to normalization of left ventricular EF a t 1 y e a r( T a b l e ). Conclusion: Although concomitant DM is related to poor outcome in patients with NI-HFrEF, appropriate glycemic control might improve cardiac function and their prognosis. 266 P-034 Azilsartan Improves Diastolic Function in Patients with Chronic Heart Failure Mari SAKAMOTO、Takahiro OHARA、Akira FUNADA、Makoto AMAKI、 Takuya HASEGAWA、Yasuo SUGANO、Hideaki KANZAKI、 Masanori ASAKURA、Toshihisa ANZAI、Masafumi KITAKAZE Department of Cardiovascular Medicine, National Cerebral and CardiovascularCenter,Osaka,Japan Background: Angiotensin receptor blocker( ARB)is reported to improve the prognosis of patients with chronic heart failure(CHF). It is not known that the effect is a class effect or not.Methods: We retrospectively assessed echocardiographic and clinical parameters in CHF patients, to whom azilsartan(Azilsartans, n=15)or candesartan (Candesartans, n=15)were newly prescribed. Results: At baseline, there were no significant differences between both groups in clinical, echocardiographic parameters, and BNP levels. At 3 months, blood pressure decreased to the similar levels in both groups. Whereas E/Ea significantly decreased in Azilsartans(13.0±4.2 vs. 10.9±3.2, p=0.03), that of Candesartans did not(12.0±3.6 vs. 12.5±5.0, p=0.58)(p for interaction=0.04, Figure). Conclusions: Azilsartan improves diastolic function in the patients with CHF. Azilsartan may be more preferable in patients with CHF than other ARBs. P-035 Effect of Telmisartan on Heart Failure in Patient with Hypertensive Cardiomyopathy Megumi SHIMADA、Akiyasu BABA、Rie KOSUGI、 Makoto AKAISHI DepartmentofCardiology,KitasatoInstituteHospital,KitasatoUniversity, Tokyo,Japan A 58-year-old man was referred to our hospital because of acute heart failure. He was diagnosed as hypertensive cardiomyopathy, and started treatment of heart failure and hypertension. After 6 months of combination therapy, we modified the treatment, and started telmisartan, then, followup examination of standard ECG-gated SPECT imaging was done. The SPECT data were reanalyzed by using new software, heart function view(Medi-Physics Co.),automatically. LVEF were used as markers of systolic function, and Peak phase, systolic phase standard deviation(Phase SD)and histogram bandwidth(Bandwidth)were used as markers of dyssynchrony. We also tested BNP concentration as a marker of heart failure. As shown in figure, telmisartan may have had favourable effects on heart failure in this case. プログラム・抄録集 ポスター8(P08)心不全を症例報告から考える P-036 The Efficacy and Safety of Febuxostat for Hyperuricemia in Hypertensive Patients with Chronic Heart Failure and Chronic Kidney Disease Toshio NAKA1)、Tomotaka ANDOU2)、Tohru MASUYAMA2) DepartmentofInternalMedicine,KaizukaCityHospital,Kaizuka,Japan、 2) Cardiovascular Division, Department of Internal Medicine, Hyogo CollegeofMedicine,Nishinomiya,Japan 1) P-037 Effect of Inhibitors of Renin-Angiotensin System on ST-segment Elevation Myocardial Infarction in Patient with Left Ventricular Ejection Fraction More Than 40% Woong JEON1)、Sang-Ho PARK1)、Seung-Woon RHA2)、Jin-Soo BYUN1)、 Dong Kyu JIN1)、Byoung Geol CHOI2)、Cheol Ung CHOI2)、 Chang Gyu PARK2)、Hong Seog SEO2)、Dong Joo OH2) CardiologyDepartment,SoonchunhyangUniversityCheonanHospital, Cheonan, Korea、 2)Cardiovascular Center, Korea University Guro Hospital,Seoul,Korea 1) Background; It has been known that the inhibitors of renin-anigotensin system(RAS)is effective on long-term survival after primary percutaneous coronary intervention(PCI)in ST-segment elevation acute myocardial infarction(STEMI)with left ventricular ejection fraction<40%. However, the benefit on clinical outcomes in STEMI with LVEF 40% has been not evaluated. Methods; We investigated the 316 patients(pts)that was presented with STEMI with LVEF 40% in Korea University Guro Hospital PCI registry database from september 2004 to june 2011. We compared 2-year clinical outcomes of pts treated with(n=229)and without(n=87)RAS inhibitor at discharge. Results; There was no statistic significance except in the incidence of total mortality(6.0% vs 12.%, p=0.037)and cardiac death(6.0% vs 0.6%, p=0.010). In multivariate logistic regression analysis, the non-use of RAS inhibitor was predictor for cardiac death(OR, 9.859; 95% CI, 1.047-92.834; p=0.045). In Kaplan-Meyer Curve, the incidence of cardiac death was higher in the nonuse group of the RAS inhibitor(figure). Conclusions; In our study, the inhibitor of RAS may be effective on cardiac death up to 2-year clinical outcome after PCI in pts with STEMI and LVEF 40%. Alterations in Ventricular Contractile Mechanisms in Heart Failure with Atrial Fibrillation Shin-Ichi USHIRODA UshirodaMedicalClinic,Fukushima,Japan Objective: The aim of this case study was to show the alterations in the ventricular contractile mechanisms in a patient with heart failure(HF)and atrial fibrillation(AF)during the course of treatment, which remained largely unknown. Methods and Results: A new ventricular function curve was created by applying(dZ/dt)min, which represents the peak value of the first derivative of the heart-synchronous thoracic impedance changes, obtained using impedance cardiography. Ventricular beats involved in postextrasystolic potentiation (PESP)were defined by preceding RR interval(RR1)/ pre-preceding RR interval(RR2)> 1 [VP(+)]. Ventricular beats not involved in PESP(Frank-Starling mechanism and mechanical restitution: FSM+MR)were defined by RR1/RR2 < 1 [VP(-)]. The ventricular function curve was divided into two regression curves of VP(-)and VP(+)based on this RR1/ RR2 ratio. The degree of PESP was represented by the slope of the regression line between the RR1/RR2 ratio( where RR1/RR2 > 1)and(dZ/dt)min of VP(+).Use of this method in a 76-year-old man with deterioration of HF with AF showed that( 1)the ventricular function curve and the regression curve of VP(-)gradually shifted upward,(2)the slope of the regression line representing the degree of PESP gradually decreased as HF with AF improved. Conclusion: In this case, contributions of FSM+MR increased, whereas the contribution of PESP decreased as HF with AF improved. P-039 The Usefulness of Ambulatory Blood Pressure Monitoring in Heart Failure Due to Nocturnal Hypertension Yusuke UEDA、Shinsuke MIKAMI、Hitoshi SUSAWA、 Kengo KOBAYASHI、Haruki TANAKA、Kouichi TANAKA DepartmentofCardiology,MiyoshiCentralHospital,Hiroshima,Japan Nocturnal hypertension is a risk factor for heart failure exacerbation.A case was 91 year-old male. He was transferred to our hospital because of sudden dyspnea. His past history were hypertension, chronic heart failure, arteriosclerosis obliterans, chronic kidney disease and left below knee amputation. Systolic blood pressure exceeded more than 200 mmHg. Chest X-ray showed pleural effusion and pulmonary congestion. We diagnosed clinical scenario one heart failure. Then, we used nicardipine hydrochloride in order to lower the blood pressure. But antihypertensive drugs were not sufficient to improve heart failure. Ambulatory blood pressure monitoring(ABPM)showed riser type blood-pressure transition. After that we shifted hypotensive drugs and diuretics from after breakfast to before sleep, pleural effusion was decreased. Blood-pressure type in ABPM changed from riser to non-dipper pattern, and heart failure was improved. We experienced that ABPM was usefull to control heart failure due to nocturnal hypertension. 267 一般演題 ︵ポスター︶ (Background)Febuxostat, a non-purine xanthine oxidase inhibitor, has been reported to have a stronger effect and more safety on hyperuricemia than allopurinol. However, there is not available on the effect of febuxostat in hypertensive patients with chronic heart failure (CHF)and chronic kidney disease(CKD) (Methods) . The aim of this study is to examine the efficacy and safety of febuxostat in hypertensive patients with CHF and CKD for treating hyperuricemia. Twenty hyperuricemic patients with hypertension(HT), CHF and CKD were enrolled and treated with febuxostat(10-20mg/day). Serum uric acid concentrations and serum estimated GFR levels in the 3 months before and after the start of febuxostat treatment were collected for HT, CHF and CKD patients switched from allopurinol after failing to achieve serum uric acid concentrations <6.0mg/dl.(Results)Evaluable data were available for 20 patients, 20% of whom had advanced CKD(eGFR<30ml/min/1.73m2). Mean dose of febuxostat was 11(± 3.7)mg/day. By using febuxostat, mean serum uric acid concentration decreased from 7.6(±1.2)mg/dl at baseline to 6.2(±0.9)&mg/dL at 3 months(p<0.001); 35% of patients achieved a level <6.0mg/dL. No serious adverse reactions were noted with febuxostat, and there were no significant changes in blood pressure, heart rate, total cholesterol, triglyceride, hemoglobin A1c, and hepatic and renal function. (Conclusions)Febuxostat was effective for hyperuricemia in patients with HT, CHF and CKD without severe side effects. P-038 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 P-040 P-042 What is the Best Treatment for Severe Tricuspid Valve Regurgitation ? Right-Sided Infectious Endocarditis Complicated with Atrial Septal Defect Naoko IKEDA1)、Mio EBATO2)、Miki TSUJIUCHI2)、 Takuya MIZUKAMI2)、Ayaka NOGI2)、Hideyuki MAEZAWA2)、 Hiroshi SUZUKI2)、Kaoru TANNO1) Mai SHIMBO、Hiroyuki WATANABE、Tatsumi ABE、 Teruki SATO、Takashi KOYAMA、Hiroshi ITO Cardiovasculerdivision,Kototoyosuhospital,Showauniversity,Tokyo, Japan、2)Cardiovasculer division, Fujigaoka hospital, Showa university, Tokyo,Japan 1) 一般演題 ︵ポスター︶ Patients with severe tricuspid valve regurgitation are increasing and we have to choose the best treatment for each patients. We evaluated whether the tricuspid valve dimension will change by various treatment. The study sample consisted of 8 chronic heart failure patients with severe tricuspid valve regurgitation and they were evaluated with echocardiography several times during hospital course. 75±9.4years old, male 25%,leg edema 75% ,pacemaker, ICDimplanted 50%,chronic atria fibrillation 87.5% admission times for heart failure 1.25±1.7/min, cases with completely unattached valve leaflets 50%,NYHA2.6±0.9,BMI 23± 6.5kg/m2,systolic blood pressure 105±11mmHg, diastolic blood pressure 60±10mmHg, heart rate 66±4.5bpm, BNP 730±770 pg/ml, eGFR 35.5 ±19ml/min/1.73m2, LVEF=67.3±2.5% We turned attention to 4 cases who have completely unattached valve leaflets and compared some echocardiac parameters before and after treatment. There were a significant correlation between reduction of RA area and reduction of tricuspid valve regurgitant area. And there were a significant correlation between reduction of RV area and tricuspid valve regurgitant area. However, there were no significant correlation between tricuspid valve dimension and reduction of tricuspid valve regurgitant area. There is little correlation between tricuspid valve dimension and the reduction of tricuspid valve regurgitation among patients with completely unattached valve leaflets. This might be the reason they are getting worse CHF. Surgical treatment would be needed to control tricuspid regurgitation. P-041 Department of Cardiovascular Medicine, Akita University Graduate SchoolofMedicine,Akita,Japan A 55-year-old female was referred to our hospital due to dyspnea and persistent fever resistant to antibiotics. Echocardiography showed secundum atrial septal defect(ASD)measuring 2 cm in diameter and moderate tricuspid regurgitation(TR)with right ventricular and right atrial enlargement. Moreover, we detected a mobile vegetation measuring 15x10 mm attached to the anterior leaflet of tricuspid valve. Chest CT showed the multiple nodules in bilateral lung parenchyma, suggestive of the septic pulmonary embolism. Blood cultures grew Gram negative bacillus. We have a strong suspicion of right-sided infectious endocarditis(RSIE). Although brain MRI showed evidences of neither stroke nor intracranial aneurysm, given the risk of paradoxical embolism, an urgent surgical treatment consisting of the removal of vegetation, tricuspid valve replacement and ASD patch-closure was performed successfully. Microscopically, friable vegetation consisted of fibrin and platelets mixed with leukocytes and bacterial colonies. A diagnosis of RSIE complicated with ASD was made. She had an uneventful postoperative course. ASD is considered to be a negligible risk for IE because of the slow shunt flow, so that RSIE with ASD is extremely rare. However, TR secondary to right ventricular overload has a potential cause of IE, once it occurs, the paradoxical embolism might lead to fetal complication. We emphasize that, unlike other RSIE, RSIE with ASD needs early surgical treatment to avoid fetal complication. P-043 A Case of Myocardial Calcification with the Latent Risk of Congestive Heart Failure Two Cases of Pulmonary Hypertension Associated with Portosystemic Shunt Shimpei ITO1)、Akihiro ENDO1)、Taiji OKADA1)、Taku NAKAMURA1)、 Tomoko ADACHI1)、Ryuma NAKASHIMA1)、Takashi SUGAMORI1)、 Nobuyuki TAKAHASHI1)、Hiroyuki YOSHITOMI2)、Kazuaki TANABE1) Haruka SATO、Tatsuo AOKI、Masanobu MIURA、Nobuhiro YAOITA、 Saori YAMAMOTO、Syunsuke TATEBE、Kotaro NOCHIOKA、 Kimio SATOH、Koichiro SUGIMURA、Hiroaki SHIMOKAWA The Forth Department of Internal Medicine, University of Shimane, Shimane,Japan、2)DepartmentofClinicalLaboratory,ShimaneUniversity Hospital,Shimane,Japan Department of Cardiovascular Medicine, Tohoku University Graduate SchoolofMedicine,Sendai,Japan. 1) An 88-year-old man was referred to our hospital because of cardiac evaluation before cholecystectomy. He had a history of rheumatic fever at 30 years old and tuberculosis at 86 years old. Electrocardiogram showed abnormal Q waves in I and aVL and negative T waves in V3-6. The results of blood test were almost within normal range. Transthoracic echocardiography demonstrated left ventricular (LV) ejection fraction was 46% and LV wall motion abnormality was detected in the posterolateral wall and apex with hyperechoic calcified mass. A CT scan confirmed the myocardial calcification at the same region. A coronary angiogram showed normal coronary arteries. Right heart catheterization revealed normal pulmonary artery pressure. However stress echocardiography revealed pulmonary hypertension during exercise. Reports of myocardial calcification are limited mainly to case reports and most reported cases have been identified postmortem. Pathologic myocardial calcification occurs by two mechanisms dystrophic and metastatic. We report an interesting case of myocardial calcification. We consider etiology of calcification was due to rheumatic fever because of his past history. His LV myocardial calcification may cause elevated LV filling pressure during exercise. 268 <Case 1> In October 2013, a 57 year-old woman admitted to a hospital for dyspnea and hypoxia. Since echocardiography showed elevated tricuspid regurgitation pressure gradient, she was transferred to our hospital. Computed tomography showed portal-hepatic vein shunt and partial anomalous pulmonary venous return. Right heart catheterization showed that she had pulmonary hypertension(PH)with elevated mean pulmonary arterial pressure( mPAP, 29 mmHg). Furthermore, micro-bubble test showed intrapulmonary shunt. Finally, she was diagnosed as having hepatopulmonary syndrome associated with portal-hepatic vein shunt. For further treatment, transcatheter embolization for portosystemic shunt is scheduled.<Case 2> In August 2013, a 25 year-old woman was referred to our hospital for examination of abnormal findings on chest X-ray with dilated pulmonary arteries. At age 9, she underwent partial splenic embolization for extrahepahc portal hypertension and at age of 11, surgical superior mesenteric vein and inferior vena cava shunting. Right heart catheterization showed elevated mPAP(72 mmHg)and high cardiac output(CO 7.3 l/ml, CI 3.2 L/min/m2). Finally, she was diagnosed as having pulmonary hypertension associated with portosystemic shunt based on her past history and hemodynamic findings. Subsequent therapy with tadalafil for 2 months decreased mPAP to 48 mmHg. We hereby report 2 cases of pulmonary hypertension associated with congenital or acquired portosystemic shunt. プログラム・抄録集 ポスター9(P09)バイオマーカーの新たな展開 P-044 Mismatch Between Brain Natriuretic Peptide and Body Fluid Status Assessed by Multifrequency Bioimpedance in Patients with Acute Decompensated Heart Failure Fumie OTOMO1)、Mitsuaki ENDO2)、Eiichi AKIYAMA3)、 Yasushi MATSUZAWA3)、Masaaki KONISHI3)、Hideo HIMENO2)、 Satoshi UMEMURA4)、Kazuo KIMURA3) Background: The natriuretic peptides have proven useful as an adjunct tool for optimizing fluid management of heart failure patients. However, in the setting of acute decompensated heart failure(ADHF), there are some cases where brain natriuretic peptide(BNP)paradoxically increases despite resolution of signs and symptoms of congestion. Therefore, we investigated the association between BNP and body fluid status assessed by multi-frequency bioimpedance(MFBIA).Methods: Consecutive twentyfour patients(81±8 years; 46% men)admitted for ADHF underwent serial BNP and edema index(EI)measurement at admission, on days 2, 5, and at discharge. EI represents a ratio of extracellular water to whole-body water on MFBIA.Results: From admission to discharge, BNP and EI significantly decreased(from 1175.2±1147.2 to 381.3±381.4pg/ ml, and from 0.415±0.011 to 0.401±0.011, respectively, both p<0.01), and changes in BNP correlated with those in EI(r=0.53, P=0.007). Nevertheless, there are no correlations between changes in BNP and EI on day 2(r=0.13, P=0.52)and day 5(r=0.26, p=0.21). A mismatch between changes in BNP and EI on day 2 was noted in 7(29%)patients, who had significantly lower tricuspid annular plane systolic excursion on echocardiography (13.2±2.5 vs. 17.4±3.6mm, p=0.008)compared to those without a mismatch.Conclusions: In patients with ADHF with right ventricular dysfunction, serial changes in BNP during the acute phase of hospitalization might not aid clinical assessments of congestion. P-045 Hyponatraemia is Associated with Elevated Pulmonary Capillary Wedge Pressure and Mortality in Patients with Chronic Heart Failure Tetsuji MORISHITA、Hiroyasu UZUI、Ken-ichiro ARAKAWA、 Naoki AMAYA、Kenichi KASENO、Kentaro ISHIDA、Takehiko SATO、 Yoshitomo FUKUOKA、Jong-Dae LEE、Hiroshi TADA DepartmentofCardiovascularMedicine,UniversityofFukui,Fukui,Japan PURPOSE: The aim of this study was to estimate the prognostic relevance of hyponatraemia and the associations with neurohormonal factors, including interleukin-6(IL-6),matrix metalloproteinase(MMP)-9 and tissue inhibitor of MMP(TIMP)-1 in patients with heart failure. METHODS: Serum sodium level, circulating levels of IL-6, MMP-9 and TIMP-1 were measured in 118 heart failure patients. Invasive hemodynamic study with dual heart catheterization was performed to measure pulmonary capillary wedge pressure(PCWP)and left ventricular enddiastolic pressure(EDP).Cardiac death and all-cause mortality were assessed during the follow-up period(average of 85±49 months).All patients were divided into four groups based on the serum sodium level; <135, 135 to 139.9, 140 to 144.9 and > 145 mmol/L. RESULTS: Hyponatraemia was found in 58.4% of the patients. A U-shaped associations of serum sodium level with PCWP and EDP were found, with lowest values in patients group with normonatraemia(P<0.05). IL-6 and MMP-9/TIMP-1 ratio increased with decreasing serum sodium level(P for trend < 0.05 and = 0.083, respectively).Kaplan-Meier analysis demonstrated a higher probability of cardiac death and all-cause death in patients group with hyponatraemia (<140 mmol/L)(P<0.05). CONCLUSIONS: Hyponatraemia indicate an increasing mortality risk in patients with heart failure. Our results suggest IL-6 and the disparity between MMP-9 and TIMP-1 contribute to the worsening hemodynamics of failing hearts with hyponatraemia. ACE2 and Ang(1-7)Concentration for Patients Urgently Hospitalized Due to Cardiovascular Disease Shinji HISATAKE、Takayuki KABUKI、Shunsuke KIUCHI、 Takashi OKA、Junichi YAMAZAKI、Takanori IKEDA Division of Cardiovascular Medicine, Department Internal Medicine, the FacultyofMedicine,TohoUniversity Background;Recently the existence of the ACE2/Ang-(1-7)/Masreceptor-axis in the RAS and the organ-protective-effect by activating this axis have been revealed. There are as yet not many reports about the transition of the ACE2/Ang-(1-7)/Mas-receptor-axis under various clinical conditions.Aim; To compare the blood concentration of ACE2 under various pathological conditions to the healthy volunteers.Methods; Among patients who were hospitalized for AHF, AMI, and acute aortic dissection between November-2012 to August-2013, 15 patients who gave their consent became the subjects of this study. At the acute stage of each disease, ACE2 and ACE, Ang-(1-7)concentration, activation of renin, AngII and aldosterone concentration were measured, and then compared and examined against a group of 10 healthy volunteers. Results; There were no significant differences in age and SBP between disease patient group(D)and healthy volunteer group(H). ACE2 concentration was significantly higher in group D compared to group H(10.52±6.12 ng/ml vs 4.83±1.91 ng/ml, p=0.004). Ang-(1-7)concentration was significantly lower in groupD than in groupH(2.35±1.50 ng/ml vs 3.66±1.29 ng/ml, p=0.035). PRA was significantly higher in groupD compared to groupH (4.23±4.68 ng/ml/h vs 1.54±0.99 ng/ml/h, p=0.047). There were no differences in ACE, Ang II, and aldosterone concentrations between the two groups.Conclusion;The patients urgently hospitalized for cardiovascular disease had higher concentration of ACE2, but lower concentration of Ang-(1-7)compared to the healthy volunteers. P-047 Surrogate Marker of Warfarin Control in Patients with Atrial Fiblliration Tatsuya KOYAMA1)、Shingo SEKI1)、Ritsu YOSHIDA1)、 Jyun HASEGAWA1)、Yoshitsugu OHKI1)、Seiko TSUNODA1)、 Tomoyuki TAKEMOTO1)、Koji YAMAZAKI1)、Michihiro YOSIMURA2) 1) Department of Cardiology, Katsushika Medical Center, The Jikei University School of Medicine, Tokyo, Japan、 2) Department of Cardiology,TheJikeiUniversitySchoolofMedicine,Tokyo,Japan Background:Atrial fibrillation is a known risk factor for thromboembolism.D-dimer levels reflect a pro-thrombogenic state and thus might serve as another marker of warfarin control. Aim:This study investigated the correlation of warfarin control marker;PT-INR and pro-thromboembolic marker;D-dimer in patients with atrial fiblliration during oral anticoagulant therapy. Method:This was a single center,retrospective study.Patients with atrial fibrillation treated with (57 males,17 females,mean age 71.8±8.7 years ) warfarin(target PT-INR: 1.5 to 3.0)were included in this investigation based on the medical chart.D-dimer levels and PT-INR were measured,and followed up to June 2014. Result:The correlation of PT-INR and D-dimer in all patients statistically was found.Espacially the negative relationship between PT-INR and D-dimer in subgroup patients,elderly patients (over 75 years) ; 28,hypertension patients; 57,patients were statistically found. Conclusion:The correlation of PTINR and D-dimer in patients of atrial fibrillation was found and thus D-dimer also can serve as surrogate marker of warfarin control. 269 一般演題 ︵ポスター︶ 1) Department of Cardiology, International Goodwill Hospital, Yokohama, Japan、2)Department of Cardiology, Fujisawa City Hospital, Fujisawa, Japan、 3)Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan、 4)Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine,Yokohama,Japan P-046 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 ポスター10(P10)肥大型心筋症の臨床 P-048 Atrioventricular Node Reentrant Tachycardia as a Cause of Recurrent Syncope in a Patient with Non-Obstructive Hypertrophic Cardiomyopathy Mariko YAGI、Tetsuo KONNO、Youji NAGATA、 Noboru FHJINO、Kenshi HAYASHI、Masayoshi KAWAJIRI、 Masakazu YAMAGISHI Departmentofcardiology,KanazawaUniversityHospital 一般演題 ︵ポスター︶ A 60-year-old male patient was admitted to our hospital for recurrent syncope. On arrival at our hospital, the patient was totally oriented. Blood pressure was 180/104mmHg, with a heart rate of 100bpm. ECG showed high voltage of precordial leads and minor ST-segment depression in lateral leads. Echocardiography demonstrated preserved left ventricular (LV)systolic function and asymmetrical ventricular wall hypertrophy. LV outflow obstruction was undetectable. Cardiac MRI demonstrated late gadolinium enhancement in the hypertrophied anteroseptal wall. Together, the patient was diagnosed as non-obstructive hypertrophic cardiomyopathy (HCM). During the hospital stay, 24-h Holter monitoring was conducted, demonstrating no pauses and no ventricular tachy-arrhythmias. Both head-uptilt test and head MRI showed no abnormal findings. On electrophysiological studies, ventricular tachycardia was not induced by extra-stimuli and basic drives from the right ventricle. However, atrioventricular node reentrant tachycardia(AVNRT)was induced by extra-stimuli of the right atrium, which resulted in sudden decrease of systolic blood pressure from 120mmHg to 50mmHg and presyncope. Subsequently, catheter ablation to the slow pathway was successfully performed, after which the patient have not suffered from syncope. HCM patients with one or more recent episodes of unexplained syncope meet indications for ICD(class IIa). Unnecessary ICD implantation in this patient was avoided by a prompt diagnosis of AVNRT, which is an uncommon cause of syncope in non-obstructive HCM. P-049 Clinical Characteristics and Prognosis in Patients with Hypertrophic Cardiomyopathy with Apical Aneurysm Seiji TAKASHIO1,2)、Megumi YAMAMURO2)、Hisao OGAWA1,2) Depertment of Cardiovascular Medicine, National Cerebaral and Cardiovascular Center, Osaka, Japan、2)Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto,Japan 1) Background: Hypertrophic cardiomyopathy(HCM)with apical aneurysm is a rare and unique form of this disease. Although there have been several reports until now, clinical characteristics and its prognosis are not fully understood.Methods and result: Between July 1996 and September 2013, consecutive 25 HCM patients with apical aneurysm(mean age 56±16 years at diagnosis, male 20)were enrolled from two referral hospitals in Kumamoto and analyzed retrospectively. Their first clinical manifestation was sustained ventricular tachycardia(Sus-VT)in 8 patients. Implantable cardioverter defibrillators( ICD)were implanted in 17 patients, including 8 patients for primary prevention. Over the follow-up period of 62±43 months(range 6-142 months), 15 patients(60%)experienced adverse clinical events( event rate: 40 %/5 years). Appropriate ICD shock and Sus-VT were occurred in 8 patients and 1 patient, respectively. Heart failure(HF)to need hospitalization was occurred 6 patients. Thrombi in the aneurysm were recognized in 5 patients. Among them, those were refractory to anticoagulant therapy in 3 patients. Thromboembolism was occurred in 1 patient. Four patients died due to electrical storm with end-stage HF, end-stage HF, and hepatic failure, respectively.Conclusion: HCM with apical aneurysm was at high risk of fatal ventricular arrhythmias, HF and apical thrombi. HCM with apical aneurysm could be a powerful predictor to consider ICD implantation and the strict anticoagulant therapy. 270 P-050 Impact of Right Ventricular Hypertrophy on Severity of Clinical Phenotypes in Hypertrophic Cardiomyopathy Yoji NAGATA、Tetsuo KONNO、Noboru FUJINO、 Akihiko HODATSU、Akihiro NOMURA、Kenshi HAYASHI、 Masa-Aki KAWASHIRI、Masakazu YAMAGISHI Department of cardiology, Kanazawa university hospital, Kanazawa, Japan Although left ventricular(LV)morphology and function have been well studied in hypertrophic cardiomyopathy(HCM), few data exist regarding right ventricular(RV)ones. We examined 59 HCM patients (36 men, age 60.5±15.0 years)who underwent cardiac magnetic resonance(CMR)exhibiting maximal LV thickness > 13 mm. RV hypertrophy(RVH), defined as RV maximal wall thickness > 5mm, was observed in 17 of 59 patients(RVH group). The RVH group showed higher brain natriuretic peptide levels( 387.7 ± 287.4 vs. 226.1 ± 217.3pg/ml, p=0.02)than those in the non-RVH group. The RVH group showed reduced RV end diastolic volume index(48.7 ± 16.0 ml/m2 vs. 64.4 ± 13.9 ml/m2, p=0.001)in accordance with greater LV mass index(110.4 ± 21.6 vs. 75.6 ± 21.4 g/m2, p < 0.0001). Interestingly, the RVH group was highly associated with RV-late gadolinium enhancement in comparison with the non-RVH group(29.4% vs. 0%).During follow up period, the RVH group had higher incidence of cardiovascular events such as heart failure admission, ventricular tachyarrhythmia/fibrillation, stroke and sudden cardiac death than that in the non-RVH group(log-rank p = 0.02). Multivariable analysis revealed that only RV maximal wall thickness was independent predictor of cardiovascular events(p = 0.03). In Conclusion, HCM with RVH determined by CMR can be associated with the higher incidence of cardiovascular events than non-RVH patients. P-051 Intravenous Cibenzoline Shifts Force-frequency Relationship Downwards and Decreases Intraventricular Pressure Gradient During Tachycardia in Patients with Hypertrophic Obstructive Cardiomyopathy Tohru WATANABE、Takeshi KASHIMURA、 Hiromi KAYAMORI、Koumei TANAKA、Hiroaki OBATA、 Tohru MINAMINO Department of Cardiovascular Biology and Medicine, Niigata University GraduateSchoolofMedicalandDentalSciences,Niigata,Japan [Background] Heart rate- dependent change of left ventricular contractile force is known as the force-frequency relationship(FFR). FFR in patient with hypertrophic obstructive cardiomyopathy (HOCM)and effects of class I anti-arrhythmic agents on it are still to be elucidated. [Methods] In 4 patients with HOCM(left ventricular outflow tract obstruction in 3, mid-ventricular obstruction in 1), FFR was assessed by the initial peak of left ventricular dP/dt during right atrial or ventricular incremental pacing before and after intravenous cibenzoline(cibenzoline succinate 1.4mg/kg). [Results] Two of the four patients showed FFR of a progressive rise during incremental pacing and their intraventricular pressure gradient remained high. One showed FFR of a progressive decrease and a concomitant decrease of intraventricular pressure gradient. The other showed biphasic FFR of initial rise and subsequent drop with sustained high intraventricular pressure gradient. Intravenous cibenzoline shifted FFR downwards and nearly abolished intraventriculr pressure gradient in 3 patients, even though the other patient with a biphasic FFR did not show apparent shift of FFR, nor did intraventricular pressure gradient. [Conclusions] Patterns of FFR vary among patients with HOCM. Cibenzoline can shift FFR downwards and diminish intraventricular pressure gradient even during tachycardia, although the effects also vary among patients. プログラム・抄録集 ポスター11(P11)虚血による心不全のメカニズムを解明する P-052 Tenascin-C Enhances Inflammaoty Response During the Ventricular Remodeling after Myocardial Infarction in Mice Model Taizo KIMURA1)、Akira SATO1)、Kazuko TAJIRI1)、 Zeng WANG1)、Toshimichi YOSHIDA2)、Michiaki HIROE3)、 Kyoko IMANAKA2)、Kazutaka AONUMA1) 1) Division of Cardiovascular Medicine, University of Tsukuba, Tsukuba, Japan、2)Department of Pathology and Matrix Biology, Mie University Graduate School of Medicine, Tsu, Japan、3)National Center for Global HealthandMedicine,Tokyo,Japan Prevention of Myocardial IschemiaReperfusion Injury in Cardiac-Specific SOCS3 Knockout Mice by Enhanced Activation of Cardioprotective Signaling Pathways Takanobu NAGATA、Hideo YASUKAWA、 Toyoharu OBA、Kazutoshi MAWATARI、Sachiko KYOGOKU、Hideki OHSHIMA、 Tomoko MINAMI、Shouichirou NOHARA、Yuusuke SUGI、Yoshihiro FUKUMOTO DepartmentofInternalMedicine,KurumeUniversitySchoolofMedicine, Fukuoka,Japan BACKGROUND: Although JAK-STAT signaling activating cytokines have been shown to prevent myocardial ischemia-reperfusion(IR)injury, little is known about the negative regulatior of the JAK-STAT pathway in the development of IR injury. We previously showed that(SOCS3)is an intrinsic negative regulaton of cytokine-induced STAT3 activation. In this study, we investigated the role of myocardial SOCS3 during IR injury. METHODS AND RESULTS: Myocardial IR injury was induced by ligation (1-hr)of LAD, followed by different reperfusion time in cardiac-specific SOCS3 knockout mice(SOCS3-CKO)and controls. Evans blue and 1% TTC staining after a 24-hr reperfusion showed a 33% reduction in myocardial infarct size in SOCS3-CKO compared to controls(p<0.05). TUNEL staining revealed that, after 6-hr of reperfusion, apoptotic cells were significantly decreased in SOCS3-CKO. STAT3 phosphorylation was faint at 1-hr after ischemia, marked at 20-min after reperfusion, and suppressed at 3-hr after reperfusion. In contrast, STAT3, AKT, and ERK1/2 phosphorylation after reperfusion was significantly greater in SOCS3-CKO than in controls. To investigate the mechanism underlying the prevention of myocardial IR injury in SOCS3-CKO, we examined expression of anti-apoptotic Bcl2 family member myeloid cell leukemia-1(Mcl-1).CONCLUSION: These results suggested that myocardial IR injury may have been prevented in SOCS3-CKO by enhanced activation of cardioprotective signaling pathways. P-053 P-055 Dipeptidyl- Peptidase 4 Inhibitor Alogliptin Attenuates Myocardial Ischemia/ Reperfusion Injury Via an Adenosine- Dependent Mechanism Evaluation of Mitochondrial ATP Levels in Vivo Identifies G0/G1 Switch Gene 2 as a Therapeutic Target of Ischemic Heart Failure Madoka IHARA1)、Satoru YAMAZAKI2)、Hiroshi ASANUMA3)、 Masafumi KITAKAZE4) Hisakazu KATO1)、Hidetaka KIOKA1,2)、Yoshihiro ASANO1,2)、 Seiji TAKASHIMA1,2) Department of Cell Biology, National Cerebral and Cardiovascular Center, Osaka, Japan、2)Department of Cell Biology, National Cerebral a n d C a r d i o v a s c u l a r C e n t e r, O s a k a , J a p a n 、 3 ) D e p a r t m e n t o f Cardiovascular Science and Technology, Kyoto Prefectural University School of Medicine, Kyoto, Japan、4)Department of Cardiovascular Medicine,NationalCerebralandCardiovascularCenter,Osaka,Japan 1) 1) Incretin therapy differs from previous DM therapies which are often limited by adverse effects such as weight gain, edema, or hypoglycemia and incretin therapy can help preserve pancreatic β-cell function. In addition to glucose control, incretin mimetics have multiple effects including cardioprotection. In DM patients, coronary artery disease is the leading cause of cardiovascular death, accounting for half of the deaths but it remains controversial whether dpp4 inhibitor can reduce the infarct size after myocardial ischemic/reperfusion injury. Therefore, we tested the involvement of dpp4 inhibitor in the infarct size-limiting effect using larger mammals and focused on the mechanism related to adenosine, which is thought to be a key player in preconditioning. In anesthetized dogs, the left anterior descending coronary artery was occluded for 90 minutes, followed by reperfusion for 6hours. Alogliptin reduced the infarct size(17.1 ± 5.0 % versus 43.1 ± 2.5 %), and this effect was completely reversed by a nonselective adenosine receptor. Alogliptin shows a cardioprotective effect against ischemia/reperfusion injury, which might arise from an adenosine -related mechanism. DepartmentofMedicalBiochemistry,OsakaUniversityGraduateSchool of Medicine, Osaka, Japan、 2) Department of Cardiology, Osaka UniversityGraduateSchoolofMedicine,Osaka,Japan <Background> Heart tissue consumes more energy than other organs to maintain cell viability and cardiac pump function. Imbalances between energy demand and supply in an ischemic myocardium fall into the mechanical failure of heart. Therefore understanding the mechanism to maintain ATP production in heart would be therapeutic strategy for ischemic heart failure. We recently identified G0/G1 switch gene 2(G0s2)as an active regulator for ATP-producing enzyme, FoF1-ATP synthase in cultured cardiomyocytes. However, whether G0s2 play roles in regulating ATP production in vivo is still unknown. <Hypothesis> In this study, we aimed to clarify whether G0s2 actually affects mitochondrial ATP production using a zebrafish model to accurately measure mitochondrial ATP concentration in vivo. <Methods and Results> To assess mitochondrial ATP production in vivo heart, we created transgenic zebrafish model that specifically expresses mitochondria-targeted FRET-based ATP biosensor(Mit-ATeam)in cardiomyocytes. Using Mit-ATeam zebrafish, we observed a decline in mitochondrial ATP concentration in the beating hearts during hypoxia and its recovery by sequential re-oxygenation. Furthermore, we expressed G0s2 in Mit-ATeam zebrafish heart and G0s2-overexpressing cardiomyocytes showed enhanced contractility with increased intra-mitochondrial ATP concentration in hypoxic condition. <Conclusion> These results suggest that G0s2 functions as a guardian of hypoxic tissue via enhancing ATP production and could become a therapeutic target for ischemic heart failure. 271 一般演題 ︵ポスター︶ Tenascin-C(TN-C), an extracellular matrix glycoprotein, transiently appeared in myocardial tissue after acute myocardial infarction(AMI). However, the biological function of TN-C in ventricular remodeling after myocardial infarction reminas to be elucidated. The aim of this study was to investigated the effects of TN-C on LV remodeling after myocardial infarction. The 8 to 10 weeks old male wild type(WT)and TN-C knock-out(KO)mice were divided into 4 groups of WT+Sham, KO+Sham, WT+myocardial infarction( MI)and KO+MI. In chronic pahse, 12 weeks post-MI, the survival rate of both WT+MI(48.3%,14 of 29 mice)and KO +MI(55.6%,15 of 27 mice)groups had no significant difference. TN-C KO group had the better cardiac function than WT had(LVEF, 19.02±6.31% vs 10.63±4.43%; p<0.001). Interstitial fibrosis at border area was significantly increased in the WT+MI group. At acute phase, fluorescence activated cell sorting(FACS)analysis showed that ratio of CD45+, F4/80+, CD206+, M2 macrophage were significantly increased in KO+MI compared with WT+MI group 7 days after MI. RTPCR analysis showed that the expression of IL-10, an anti-inflammatory cytokine, was significantly higher in KO+MI than WT+MI at acute phase. In conclusion, TN-C aggravates the deterioration of LV function in chronic phase after MI partly through accerelation of inflammation via suppression of the anti-inflammatory M2 macrophage at acute phase. P-054 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 ポスター12(P12)心不全に対する新たな薬物療法の可能性 P-056 P-058 Post-Infarct Treatment with microRNA145 Protects the Heart Against Myocardial Ischemia-reperfusion Injury through Acceleration of Myocyte Autophagy 1) 1) Effects of a Selective Acetylcholine-activated Potassium Channel Blocker on the Regulation of Heart Rate 4) Kenshi HIGASHI 、Yoshihisa YAMADA 、Takuma AOYAMA 、 Shinya BABA1)、Shingo MINATOGUCHI1)、Kazuhiko NISHIGAKI1)、 Genzo TAKEMURA3)、Yukihiro AKAO2)、Shinya MINATOGUCHI1) Gifu University Graduate School Of Medicine, Gifu, Japan、 United Graduate School of Drug Discovery and Medical information Science, Gifu University, Gifu, Japan、3)Asahi University, Gifu, Japan、4)Kizawa memorialhospital,Gifu,Japan 1) 2) 一般演題 ︵ポスター︶ Background: We previously reported that microRNA145(miRNA145)significantly reduced the myocardial infarct size and improved the function of left ventricle. It has been reported that autophagy is activated in cardiomyocytes in ischemic heart disease. We investigated whether miRNA145 reduces the myocardial infarct size through acceleration of autophagy.Objective: We aimed to investigate whether administration of miRNA145 would affect myocyte autophagy in a rabbit model of myocardial infarction.Methods: Male Japanese white rabbits underwent 30 min of coronary occlusion followed by 14 days of reperfusion, then received intravenous injection of saline or miRNA145(0.035 mg/kg)immediately after reperfusion. At 14 days after reperfusion, rabbits were sacrificed and the hearts were removed. Heart tissues were sampled and devided them into three area; remote area, borderline area and infarct area. The morphological changes were investigated by electron microscopy, and the expressions of LC3B were assessed by western blot analysis. Results: Electron microscopy findings showed that cardiomyocyte autophagy was observed in both control and miRNA145 groups. Western blot analysis showed that transition from LC3B-1to LC3B2 were stronger in miRNA145 group than in the control group.Conclusions: It is suggested that post-infarct treatment with miRNA145 attenuated ischemiareperfusion injury through acceleration of myocyte autophagy. This was confirmed by western blotting analysis of LC3B. P-057 Noriaki YAMADA1)、Yoshihiro ASANO1)、 Satoru YAMAZAKI2)、Tetsuo MINAMINO1)、Yasushi SAKATA1)、 Masafumi KITAKAZE2)、Seiji TAKASHIMA1) 1) Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine、 2)National Cerebral and Cardiovascular Center ResearchInstitute Sinus bradycardia causes a decreased cardiac output resulting in a variety of clinical symptoms. From a pedigree of familial sinus bradycardia, we previously identified a novel missense mutation in the KCNJ3 gene. KCNJ3 is a member of heterotetrameric acetylcholine-activated potassium channel(KACh channel)in the sinus node, atrioventricular node, and atrial myocardium. The mutation is located in the M1 helix of KCNJ3, which forms the transmembrane pore of the KACh channel. Electrophysiological analyses demonstrated that the KCNJ3 mutation increased the basal current amplitude, and the increased current flow through KACh channels leads to sinus bradycardia. This result suggests that a pharmacological approach to the KACh channel would modulate the heart rate in vivo . We hypothesized that a novel selective KACh channel blocker is a hopeful candidate for the up-regulation of heart rate. We investigated the electrophysiological effects of this drug on the KACh channel activity by two-electrode voltage clamp analysis using Xenopus oocytes. This drug efficiently blocked the potassium current mediated by the KACh channel in the mutant as well as wild type. Furthermore, we generated transgenic zebrafish bearing atrium specific expression of the human KCNJ3 mutant for pharmacological intervention. The transgenic zebrafish showed marked bradycardia. In conclusion, functionally-altered KACh channels cause the pathogenesis of sinus bradycardia, and the KACh channel might be a therapeutic target of heart rate regulation. P-059 Angiotensin II Vaccination Suppresses Cardiac Remodeling after Myocardial Infarction Tranilast, Orally Active TRPV2 Antagonist, Ameliorates End-Stage Heart Failure in Mice with Dilated Cardiomyopathy Ryo WATANABE、Mitsuaki ISOBE Kazuo KOMAMURA、Yuko IWATA Department of Cardiovascular Medicine, Tokyo Medical and Dental University Research Institute, National Cerebral and Cardiovascular Center, Suita, Japan A growing body of evidence suggests that angiotensin II (AngII)plays a crucial role in the pathogenesis of cardiac remodeling after myocardial infarction(MI), which in turn leads to heart failure. We here examined whether a vaccination against AngII can be effective strategy to prevent cardiac remodeling after MI. Male Sprague-Dawley rats were injected subcutaneously with saline(n=7)or AngII vaccine, a conjugate of AngII and keyhole limpet hemocyanin(5µg/rat, n=11), on day 0, 14 and 21. On day 28, these rats were subjected to permanent left anterior descending coronary artery ligation. Then, hearts of these rats were harvested on day 56. The anti-AngII antibody titer was increased in the AngII vaccine-injected group [half-maximum binding titer(OD50): AngII vaccine=2595±788 vs. saline=N.D.]. Although no significant differences of blood pressure or infarct size were observed between two experimental groups, left ventricular(LV)dysfunction and infiltration of macrophages in myocardium were milder in the AngII vaccine injected-group than in the saline-injected group [LV ejection fraction: AngII vaccine=41.3±2.8% vs. saline=30.7±2.6%, p<0.05; infiltration of macrophages: AngII vaccine=65±18 cells/field vs. saline=119±9 cells/field, p<0.05]. Furthermore, AngII vaccination did not cause any detrimental changes in cardiac function and myocardium in sham-operated rats. These results suggest that the AngII vaccine may provide a novel promising therapeutic strategy to prevent cardiac remodeling after MI. Background Expression of transient receptor potential vanilloid 2( TRPV2), a calcium-permeable cation channel, increased in the sarcolemma of animal and human myocardium with dilated cardiomyopathy(DCM). We assessed whether a TRPV2 antagonist, tranilast, ameliorated heart failure of DCM mice. Methods and Results We used 4C30 mice, which has abnormal myocardial calcium handling, as a model of DCM. Sixteen 4C30 mice of 25 weeks old with end-stage heart failure were given no drug(control)or 20 mg/kg/day of carvediol (group C)or 400 mg/kg/day of tranilast(group T)or both of them(group B)for 2 weeks. Blood pressure and heart rate were similar among the 4 groups. Echocardiography demonstrated tranilast improved fractional shortening(in %). Control: 6.2±2.5; Group C: 14.2±5.6, NS; Group T: 16.6±2.3, p<0.05; Group B: 17.2±3.2, p<0.05. Tranilast also improved cardiac hypertrophy measured with heart-to-body weight ratio(in mg/ g). Control: 12.4±2.5; Group C: 11.5±3.4, NS; Group T: 8.6±0.9, p<0.05; Group B: 5.9±1.1, p<0.01. Sarcolemmal expression of TRPV2 measured with immunostaing in 4C30 mice increased twice as much as syngeneic C57BL/6J. Tranilast, not carvedilol, halved the expression of TRPV2, corresponding to reduction in [Ca2+]i of isolated cardiomyocytes. Conclusion Tranilast ameliorated heart failure in 4C30 mice, possibly due to the inhibition of Ca2+ influx through TRPV2. 272 プログラム・抄録集 ポスター13(P13)重症心不全から心不全終末期への対応 P-060 P-062 Nifedipine Attenuates Cardiac Hypertrophy by Inhibiting Nox4-induced Oxidation of HDAC4 1) 1,2) Junichi MATSUMOTO 、Shouji MATSUSHIMA 、 Shintaro KINUGAWA1)、Hiroyuki TSUTSUI1)、 Junichi SADOSHIMA2) 1) Depertment of Cardiovascular Medicine, Hokkaido University Gradiate School of Medicine, Sapporo, Japan、2)Rutgers New Jersery Medical School,Newark,USA P-061 Role of FOXO Transcription Factors in the Protective Mechanism by Resveratrol Against Cardiomyopathy in the Dystrophin-deficient Mdx Mouse Atsushi KUNO、Rio SEBORI、Yoshiyuki HORIO、Tetsuji MIURA Department of Pharmacology, Sapporo Medical University, School of Medicine, Sapporo, Japan、2)Department of Cardiovascular, Renal and MetabolicMedicine,Sapporo,Japan 1) [Purpose] We previously reported that treatment with resveratrol, an activator of the NAD+-dependent protein deacetylase SIRT1, ameliorates cardiomyopathy in the dystrophin-deficient mdx mouse. Since SIRT1 is known to activate FOXO transcription factors under stress conditions, we hypothesized that FOXO play roles in protection by resveratrol in the mdx heart. [Methods and Results] Mdx mice were divided into untreated(RSV0)and resveratrol-treated(400 mg/kg chow, RSV400)groups. Resveratrol administration was started at 8-week-old, and mice were sacrificed at 65-weekold. Echocardiography at 62-week-old demonstrated that left ventricular (LV)fractional shortening was higher(38±2% vs. 34±1%, P<0.05),IVS thickness was thinner, and end-diastolic LV dimension was smaller in RSV400 than those in RSV0. Compared with untreated mdx, resveratrol treatment significantly up-regulated cardiac mRNA levels of genes known as FOXO's targets including anti-oxidant catalase(+2.0-fold), SOD1(+2.8-fold)and autophagy-related LC3b (+2.5-fold), Bnip3(+4.1-fold). Dihydroethidium staining for analysis of cardiac reactive oxygen species revealed that fluorescence intensity was significantly decreased by 45% by resveratrol treatment. Immunoblot showed that total myocardial LC3 protein level was rather decreased in RSV400, suggesting promotion of autophagic flux by resveratrol. Nuclear FOXO3a level assessed by immunostaining was increased in RSV400 compared with RSV0. [Conclusion] Resveratrol ameliorated cardiomyopathy in mdx mice probably by attenuation of oxidative stress and induction of autophagy via FOXO activation. 楠川 翠里 1)、角田 あゆみ 1)、平田 理利佳 1)、岡本 佳子 1)、佐藤 琢磨 2)、 瀬口 理 2)、簗瀬 正伸 2)、中谷 武嗣 2) 1) 国立循環器病研究センター 看護部 重症心不全・移植病棟、2)国立循環器 病研究センター 移植部 植込型左心補助人工心臓 (以下植込型 LVAS) の管理において、 ドライブライン貫通部の管理は特に重要であり、貫通部が感 染症を引き起こし重篤化すると生命の危機に直結する。当病 棟では、創傷治癒過程及び ADL に応じた固定方法を検討し ているが、 固定方法が継続できないという現状がある。 そこで、 重症心不全移植病棟に勤務する看護師 13 名に、植込型 LVAS ドライブラインの固定についてどのように考え、実践してい るのか、質問紙を用いてアンケート調査を行った。その結果、 「患者の状態に応じた固定を継続できている」の質問に対し、 「はい」は 38%であった。それに対し、 「いいえ」は 62% で、個 別性があり複雑で分かりにくいという意見があった。植込型 LVAS は機種により、また同じ機種でも患者により固定方法 が違うという難しさがある。患者の状態にあった固定方法が 検討・継続するためには、アセスメントや注意点も含め、記 録に残すことも有効だと考える。 P-063 介護老人保健施設で行う慢性心不全患者に対する 認知症アプローチ 村井 達彦 介護老人保健施設プランタンおおまま 【はじめに】高齢化とともに認知症を合併する心不全患者が増 加している . 特に介護老人保健施設(以下老健)では , 心不全患 者のほとんどが認知症と診断されている【目的】 . 老健に入所し ている慢性心不全患者に対して認知症予防を含めた有酸素運 . 対象は平成 動プログラムを行い , その効果を検証した【方法】 24 年 10 月から平成 25 年 1 月までの間に当施設に入所していた 93 名のうち認知症を合併する慢性心不全患者 10 名を対象とし た . 介入は施設長の許可得て行われ , 利用者から文書で同意を 得た . プログラムは週1回の認知活動と有酸素運動を行った . 介 入は 3 人の小集団で行ない , 効果検証には Mann-Whitney 検 定 を 用 い た . 評 価 指 標 に は MMSE, Barthel index, Vitality . 介入前後の比較では index, DBD, ISWT,FBS, を用いた【結果】 Vitality index が介入前に比べて有意に改善していた (p<0.05). 【考察】日本の高齢化が進行するに伴い認知症を合併する慢性 心不全患者は増加傾向にある . 認知症患者にとって意欲低下 は更なる認知症上の悪化につながるため , 本研究のプログラ ムは慢性心不全患者の認知症予防の一手段として活用できる 可能性がある . 273 一般演題 ︵ポスター︶ <Rationale> NADPH oxidase 4(Nox4)is a major source of ROS in the heart and induces cardiac hypertrophy through oxidation and nuclear exit of HDAC4.<Hypothesis> We hypothesized that nifedipine, an L-type Ca2+ channel blocker, inhibits Nox4-induced oxidation of HDAC4, thereby attenuating pathological hypertrophy.<Methods and Results> A subpressor dose of phenylaphrine(PE; 20 mg/kg/day)or saline alone was continuously infused into mice with or without nifedipine(10 mg/kg/ day)via osmotic mini-pumps. After 14 days, aortic pressure was similar among the four groups. Left ventricular weight/tibial length(5.6±0.2 vs. 6.1±0.2 mg/mm; p<0.05)and cardiomyocyte cross-sectional area(223±12 vs. 268±18 μm2; p<0.05)were significantly smaller in the PE+nifedipine group than in the PE+saline group. Nifedipine caused a significant decrease in PE-induced upregulation of Nox4 in the heart, accompanied by suppression of phosphorylation of NF-κB, a transcriptional factor that upregulates Nox4. Nifedipine inhibited PE-induced upregulation of Nox4 and nuclear ROS production(Lucigenin chemiluminescence assay: 3982 ±941 vs. 7218±1945 relative light unit; p<0.05)in cardiomyocytes. PEinduced nuclear exit of HDAC4 and HDAC4 oxidation, as evaluated with biotinylated iodoacetamide assays, were also attenuated in cardiomyocytes treated with nifedipine.<Conclusion> Nifedipine inhibits pathological hypertrophy in the heart by inhibiting upregulation of Nox4 and oxidation of HDAC4, a critical redox signaling pathway in pathological hypertrophy. 植込型左心補助人工心臓のドライブライン固定方 法についての看護師の意識調査 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 P-064 P-066 介護老人保健施設に入所する認知症を合併する高 齢慢性心不全療養者の対応困難な状況と看護支援 心不全終末期患者のスピリチュアルペインの分析 ∼心不全終末期患者のインタビューを通して∼ 大津 美香 小田 真澄、夏迫 里奈、木本 直子 弘前大学大学院 保健学研究科 独立行政法人国立病院機構鹿児島医療センター 一般演題 ︵ポスター︶ 1 研究目的 : 認知症を合併する高齢慢性心不全療養者の心不全 の疾病管理の支援に際して、看護職員は対応に困難を感じて いるといわれている。再入院を繰り返す居宅以外の生活場所 として、介護老人保健施設が上位に挙げられ、対応困難によ り支援が円滑に行われていない可能性が推察された。そこで 本研究では、介護老人保健施設に入所する認知症を合併する 高齢慢性心不全療養者の対応が困難な状況と看護支援につい て明らかにする。2 研究方法 : 全国の介護老人保健施設 1,000 件の看護職員各 1 名を対象に、無記名の自記式質問紙調査を 郵送にて実施した。研究者の所属する大学の倫理委員会にお いて承認を得て実施した。3 結果 : 看護職員 106 名から有効回 答を得た。認知症を合併する高齢慢性心不全療養者では自覚 症状に乏しいうえ、心不全の客観的な症状の把握が難しいこ とから、心不全の症状および悪化症状のモニタリングに困難 を抱いていたが、悪化の予防や水分過剰摂取への対応に向け ては、医師へ報告及び相談をしていた。4 考察 : 介護老人保健 施設では常勤医師が配置されていることから、医師の協力を 得られやすい環境にあり、悪化の早期発見へとつながるもの と考えられた。 P-065 有効な終末期の支援ができた慢性心不全患者の一症例 神保 美里 1)、林 亜希子 1)、松田 美紗子 1)、成毛 崇 2)、猪又 孝元 2)、 松野 時子 1)、阿古 潤哉 2) 北里大学病院 看護部、2)北里大学 医学部 循環器内科学 1) 背景:心不全は増悪と寛解を繰り返しながら重篤化していく ため、予後の予測が困難であり、終末期のケアにおいてジレ ンマを抱えるケースが多い。今回、緩和ケアが積極的に提供 できた症例を通し、介入の有効性を検討したので報告する。 患者紹介:70 歳男性。慢性心不全で入退院を繰り返し、低心 拍出症状を呈し緊急入院となったが、徐々に治療への抵抗性 が見られるようになった。看護の実際 : 医療チームで患者が 終末期にあることを共通認識したうえで、患者・家族に現状 が伝えられた。緩和ケアチームの介入を得て、身体的苦痛の 軽減を図った。また、患者家族との話し合いの場を十分にもち、 その人らしい生活に近づけるケアを提供した。患者は愛犬と の面会を希望し、医師・家族の協力を得て、外来玄関での愛 犬との面会を実施した。傾眠傾向ではあったが、面会の際に はしっかりと開眼し、生きている実感が得られていた。 その後、 残された時間を家族とともに穏やかに過ごされ、永眠となっ た。考察: 終末期である事実を医療者・患者家族が共通認識 すること、残された時間を患者がその人らしく過ごせるよう 支援できたことで、患者家族にとって有効な緩和ケアが提供 できたと考える。 274 【背景】非がん領域での終末期医療では具体的方向性の支援が 認識されていない現状があり、先行研究でも看護の方向性に ついては明らかにされていない。【目的】心不全終末期患者の 疾患や予後に関する思いの傾向と看護の方向性を明らかにす る。 【対象・方法】 DNAR の方針を受容した患者を対象として、 疾患の受け止め方を 「緩和ケアマニュアル」 (第 5 版)を参考に カテゴリー化し、村田理論を用いて看護の方向性を分析した。 【結果・考察】「回復への期待」「退院後の生活への不安」「進 行している心不全への驚き」 「回復するか分からないことへの 藤」 が新たなスピリチュアルペインとして存在した。また今 後の看護の方向性については、 村田理論の自立存在、関係存在、 時間存在の中でも、心不全終末期患者には時間存在を意味す るスピリチュアルペインが少なかった。予後の予測が難しい ことから、心不全終末期患者の経過、特徴をよく理解し、患 者自身が疾患を抱えたうえで、今後どうしたいか、どう生き たいかの意思決定を早期から行えるような支援が重要である。 プログラム・抄録集 ポスター14(P14)心不全患者の心臓リハビリテーション P-067 P-069 複数の心臓リハビリテーション進行阻害要因を有 するCABG/CRT-D埋め込み後重症心不全の一例 鈴木 裕二 1)、山本 壱弥 1)、福井 教之 1)、小西 治美 1)、熊坂 礼音 1,2)、 荒川 鉄雄 1,2)、大原 貴裕 1,2)、中西 道郎 1,2)、後藤 葉一 1,2) 1) 国立循環器病研究センター 心血管リハビリテーション科、2)国立循環器病 研究センター 心臓血管内科 金子 奈央 1,2)、高橋 仁美 3)、山嵜 継敬 4) 1) 川崎幸病院 リハビリテーション科、2)弘前大学大学院 保健学研究科、3)市 立秋田総合病院 リハビリテーション科、4)川崎幸病院 循環器科 【目的】急性心不全患者に対する早期リハビリ介入が在院日数 に与える影響を調べるため,在院日数と座位,立位,歩行の それぞれの開始日との関連性について検討した.【対象と方 法】対象は,2012 年 6 月 1 日∼ 2013 年 10 月 31 日の間に当院循 環器科にて急性心不全 (CS 分類 1 ∼ 2)と診断された入院患者 230 名である.CS1 群と CS2 群に分け,在院日数と座位,立位, および歩行の開始日を調べ, これらの相関を検定した. 【結果】 CS2 群は CS1 群に比べ,在院日数が有意に長く,座位,立位, 歩行のそれぞれの開始日が有意に遅かった.在院日数との相 関分析では,CS1 群は座位,立位,歩行のいずれの開始日と も相関関係を認めなかったが,CS2 群は座位,立位,歩行の いずれの開始日とも中等度の有意な正の相関を認めた. 【考察】 心不全患者の高齢化が進んでおり,長期臥床による廃用症候 群を防ぐためにも安全な早期離床が重要になると考える.急 性心不全の病態や治療上,積極的なリハビリが実施できない 状況にあっても,座位などの早期リハビリ介入は在院日数を 短縮させる可能性があると考えられる. P-068 P-070 強心薬持続投与下で心臓リハビリテーションを実 施した重症心不全の一例 高齢心不全患者の入院期ADLとリハビリテー ションの検討 安川 悠仁 1)、小林 聖典 1)、清水 美帆 1)、土川 洋平 1)、澤村 昭典 2)、 深谷 兼次 2)、奥村 貴裕 2)、室原 豊明 2) 大浦 啓輔 1)、越智 裕介 1)、高橋 実希 1)、後藤 賢治 2) 名古屋大学医学部附属病院 リハビリテーション部、 名古屋大学大学院医 学系研究科 循環器内科学 1) 2) 【背景】強心薬持続投与下の重症心不全患者における心臓リハ ビリテーション(心リハ)の有効性・安全性は確立されていな い。今回重症心不全患者に対し強心薬持続投与下で心リハを 行い、自宅退院に至った症例を経験したので報告する。【症 例】 57 歳男性、基礎疾患は薬剤性心筋症。心不全で入院後、 6 病 日 よ り 心 リ ハ を 開 始 し た( 開 始 時 LVEF22%、E/e 19.6、 BNP1513pg/ml、 膝 伸 展 筋 力 60.8kgf/kg)。30 病 日 に VT が 出現し心リハを中止した。38 病日、ICD 植込み術施行後より 心リハを再開した。強心薬持続投与下での心リハプログラム は、下肢筋力強化中心の身体機能維持、心不全疾病管理、栄 養・運動指導を継続した。心不全症状の増悪に注意しなが ら、強心薬の漸減とともに心リハプログラムを拡大した。リ ハ再開時、膝伸展筋力は 48.6kgf/kg に低下していたが、116 病日、心機能・身体機能の改善を認め自宅退院に至った(退院 時 LVEF34%、E/e 8.4、BNP153pg/ml、膝伸展筋力 71.5kgf/ kg) 。運動中の VT、血圧低下等の有害事象発生はなかった。 【考 察】 重症心不全患者に対し、強心薬持続投与下においても下肢 筋力を保つことで、退院時は良好な身体機能まで改善できる 可能性が示唆された。 福山循環器病院 リハビリテーション課、2)福山循環器病院 循環器内科 1) 【はじめに】高齢心不全患者は増加傾向であり、病態が安定し ても ADL 低下が問題となる。ADL 低下にはリハビリテー ションが重要であり、本研究では高齢心不全患者の ADL と リハビリテーションについて検討した。【方法】対象は、当院 にて 2014 年 3 月∼ 5 月の間に心不全急性増悪で入院しリハビ リテーションを施行した患者 68 例 (年齢 77±10 歳、男性 41 例)。 80 歳以上(O 群)と未満(C 群)の 2 群に分け調査した。 【結果】 O 群は 35 例 (51%) 認めた。O 群は有意に女性が多く、BMI が 低値であった (p<0.01) 。ADL は barthel index が入院時 O 群 86±17 点、C 群 96±12 点と O 群が有意に高値であり(p<0.01)、 退院時 O 群 85±19 点、C 群 96±11 点と変化を認めなかった。 ADL が 入 院 中 に 低 下 し た 症 例 は O 群 2 例(6 %)、C 群 1 例 (3%) と両群に有意差を認めなかった。リハビリテーション開 始時期は O 群 3±2 日、C 群 4±3 日であり、歩行開始までの日 【考察】 数は O 群 4±3 日、C 群 4±3 日と有意差を認めなかった。 高齢心不全患者は入院前より ADL 低下を認めるが、リハビ リテーションを 80 歳未満の患者と同様に実施することにより 入院中の更なる低下を予防できる可能性が示唆された。 275 一般演題 ︵ポスター︶ 【はじめに】心不全・陳旧性心筋 塞・重症不整脈・CABG 術後・ CRT-D 埋込・高度デコンディショニングなど複数の心臓リハ ビリテーション (心リハ)進行阻害要因を有する症例を経験し た。 【症例】67 歳男性。今回、意識消失・VT 発症後第 7 病日に当 院転院。CAG にて 3 枝病変、低心機能(EF 26%)を認め、緊 急 CABG 施行。術後、治療抵抗性心不全に対し IABP 管理、 第 20 病日に IABP 抜去、第 26 病日に病棟リハビリ開始。術後 も VT・VF が出現し、第 45 病日に CRT-D 埋込術、第 53 病 日に心リハ室にて運動療法開始となった。 【方法・結果】心リハ初日、歩行負荷試験後に血圧低下し(BP 60/mmHg)、 ス ト レ ッ チ ャ ー で 帰 室。 第 2 日、 降 圧 薬 減 量 に も か か わ ら ず リ ハ 来 室 時 BP 70/48mmHg。 座 位 レ ジ ス タンストレーニング施行。以後、徐々に運動メニューを増 量、CRT-D 埋込例につき上限心拍数は 140bpm とした。第 61 病日に退院。心リハ 3 ヶ月終了時、膝伸展筋力が +16%、 PeakVO2 が +32% 増加した。 【結語】複数の心リハ進行阻害要因に対し適切に対処して心リ ハを行った結果、筋力・運動耐容能の良好な改善を認めた。 急性心不全患者の在院日数と離床との関係 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 ポスター15(P15)急性心不全の臨床 P-071 P-073 心不全患者に対する外来リハビリテーションの有用性 1) 1) 1) 1) 1) 渡邊 暢 、清川 憲孝 、佐藤 清佳 、高橋 仁美 、柏倉 剛 、 藤原 敏弥 2)、柴原 徹 2)、池田 研 2)、中川 正康 2) 市立秋田総合病院 リハビリテーション科、2)私立秋田総合病院 循環器内科 1) 一般演題 ︵ポスター︶ 【目的】入院中心臓リハビリテーション(リハ)を施行した後, 外来でリハを継続する効果について検討した.【対象】入院中 にリハを施行した心不全患者 17 名を対象とし,外来でリハを 継続した 11 名(リハ継続群)と,退院後は在宅での運動のみ指 導した 6 名 (自主トレ群)の 2 群に分け,比較検討した.【方 法】2 群とも入院中のリハは同様に行い,退院後のリハは個別 に設定,指導した.リハ継続群は週 1 回通院し,他の日は自 宅で運動を行った.自主トレ群は自宅での運動のみ行った. 2 群の 6 分間歩行距離(6MWD),握力,下肢筋力 ,BMI, 血液 生化学検査をリハ開始時と 3 カ月後に評価し,比較した.ま た,自宅での運動時間も聞き取りにより調査した.【結果】リ ハ 継 続 群 は 6MWD が 427.3 → 466.1m, 下 肢 筋 力( 体 重 比)が 49.3 → 58.7% と有意な改善があり,自主トレ群に有意な変化 はなかった. 1 週間の運動時間は自主トレ群の 46 分に対し, リハ継続群が 205 分と有意に多かった.【まとめ】外来でリハ を継続した患者は 3 ヵ月後の運動機能に改善がみられ,外来 リハの有用性が示唆された. P-072 外来心臓リハビリテーション参加継続の動機付け 支援に対するCNSの役割 藤井 利江 1)、高橋 敬子 2) 兵庫医科大学病院 看護部、2)兵庫医科大学医学教育センター 1) 【目的】外来心臓リハビリテーション(CR)参加には,動機付 けが重要である.患者が CR を心疾患の治療として捉えてい ないこと,医療者側も CR 参加への動機付け支援が十分でな い現状がある.当院は CR チームに心疾患をサブスペシャリ ティとする慢性疾患看護専門看護師(CNS)を加え,包括的外 来 CR を実施している.今回,治療中断のリスクが高く,行 動変容の意思がない患者に,CNS が行った動機付け支援から 役割を考察する. 【事例】拡張型心筋症の 40 歳代男性.無職,独居,高度肥満が あり,医療者とのコミュニケーションや内服アドヒアランス が悪く,入退院を繰り返した. 【方法】診療録から動機付け支援の内容を抽出し分析した.倫 理的配慮は,対象に研究目的,協力は自由意思,匿名性の保 持を説明し同意を得た. 【結果】 CNS が毎週電話による問診と生活指導を繰り返したと ころ,コミュニケーションが得られ,患者の CR 参加を促し, 運動習慣の萌芽と再入院の回避をもたらした. 【考察】CNS は,個々の患者に適確な助言を与えることができ, 患者自身のヘルスリテラシーの向上や外来 CR 参加継続の動 機付けを得る可能性があり,心不全チーム医療において CNS の役割は重要である. 276 A Case of Heart Failure Due to Tachycardiainduced Cardiomyopathy Kenji TAKEDA Departmentofcardiology,OkayamaSaiseikaiGeneralHospital A 55 years old man with dyspnea visited our hospital. Chest X-ray showed cardiac enlargement and pulmonary congestion. The ECG showed atrial fibrillation of heart rate 160 bpm. The echocardiography showed diffuse severe hypokinesis of left ventricular (LV) .LV ejection fraction was 16.9%. We started intravenous administration of landiolol for heart rate control. Also, we treated with vasodilator and a diuretic. Cardiac rehabilitation started after heart failure improvement. Late Gadolinium enhancement was observed at intramural segment of interventricular septum in the cardiac MRI. There is no significant stenosis by the coronary arteriography. Myocardial biopsy showed mild hypertrophy, mild fibrosis and no disarray. The systolic function was improved in the echocardiography at the 44th day of illness. The abnormality of the fatty acid metabolism was not found in the BMIPP scintigraphy after the systric function improvement. We reported a case of heart failure due to tachycardia-induced cardiomyopathy. P-074 Neuroleptic Malignant Syndrome Presennting Severe Acute Heart Failure: as an Initial Manifestation Autopsy Case Minoru WAKASA、Hirohumi AOKI、Kouji KAJINAMI TheDepartmentofCardiology,KanazawaMedicalUniversity,Uchinada, Japan A-20-year-old man was admitted to our hospital because of dyspnea. He had a 6-year history of depression treated with psychotropic drug. One week prior to admission, he developed nocturnal dyspnea. At admission, echocardiography showed diffuse severe hypokinesis of left ventricle, which was confirmed by left ventricular angiography without any coronary artery stenosis. Furthermore endcardial biopsy revealed no histopathlogical findings suggesting cardiomyopathy and carditis. Initial treatment with diuretics and inotropic agent did not improve cardiac function, resulting in endtracheal intubation.Two (39.0° C) in association days after admission, he became febrile with CK increased (482 to 4860IU/l) .We diagnosed as having neuroleptic malignant syndrome and started dantrolene administration.Level of CK decreased, however he continued to have a high fever sustained and ultimately he died at six days after admission. Taken together with autopsy findings, potential mechanism of cardiac dysfunction in the present case will be discussed. プログラム・抄録集 P-075 P-077 Thrombus Detected in Right Atrium and Inferior Vena Cava in Patient with Tachycardia Induced Cardiomyopathy Effect of Non-invasive Positive Pressure Ventilation on Outcome in Patients with Acute Heart Failure Takuya MIZUAKAMI1)、Naoko IKEDA2)、Hideyuki MAEZAWA1)、 Miki TSUJIUCHI1)、Ayaka NOGI1)、Mio EBATO1)、 Hiroshi SUZUKI1) Mitsutoshi ASAI1,2)、Kazunori KASHIWASE1)、Akio HIRATA1)、 Takayoshi NEMOTO1)、Koshi MATSUO1)、Masato OKADA1) Department of Cardiology, Showa University Fujigaoka Hospital, Kanagawa, Japan、2)Department of Cardiology, Showa University Koto ToyosuHospital,Tokyo,Japan 1) P-076 The Factors Associated with Successful Treatment with Non-invasive Positive Pressure Ventilation for the Patients with Acute Heart Failure 2) Background; Non-invasive positive pressure ventilation (NPPV)has been established for patients with acute heart failure( AHF). However, many patients cannot be discharged home after treatment, although NPPV can avoid endotracheal intubation(ETI).Objective; We examined the factors that influenced whether or not the patients could be discharged home among the patients with AHF treated with NPPV.Methods and results; We analyzed 784 patients with AHF who admitted to Osaka Police Hospital between January 2010 and December 2012. The patients( n=110)treated with NPPV without ETI were divided into those who were discharged home(H group; n=82)and those who died during hospitalization or those who were transferred to other hospital for a longer chronic treatment( DC group; n=28). The blood pressure, heart rate, respiratory rate, LVDd, and LVEF on admission were not different between the groups. On the other hand, the patients treated with continuous sedation(21% vs. 5%, p=0.01)and those who suffered pneumonia(55% vs. 21%, p=0.07)were more frequent in DC group than in H group. Conclusions; The use of continuous sedation and suffering pneumonia were negatively associated with the outcome among the patients with AHF treated with NPPV. P-078 演題取り下げ Mitsutoshi ASAI1,2)、Kazunori KASHIWASE1)、Akio HIRATA1)、 Takayoshi NEMOTO1)、Koshi MATSUO1)、Masato OKADA1)、 Yasunori UEDA1) Cardiovascular Division, Osaka Police Hospital, Osaka, Japan、 Cardiovascular Division, Higashiosaka City General Hospital, Osaka, Japan 1) 2) Background; Non-invasive positive pressure ventilation(NPPV)has been established for patients with acute heart failure(AHF). Under the expanding indication of NPPV use, we sometimes experience the cases in which NPPV treatment is not successful and endotracheal intubation(ETI)is required.Objective; We examined the factors associated with successful NPPV treatment among the patients with AHF.Methods and results; We analyzed 784 patients with AHF who admitted to Osaka Police Hospital between January 2010 and December 2012. Initially, 640 patients of them were treated with standard oxygen therapy, 121 patients with NPPV, and 23 patients with ETI. Among 121 patients initially treated with NPPV, the treatment was not successful in 11(9%)patients who required ETI(F group)while the treatment was successful in the rest of the patients (S group).The blood pressure, heart rate, respiratory rate, LVDd, and LVEF on admission were not different between the groups. On the other hand, PCO2 was significantly higher(60.4±30.6mmHg vs. 47.1± 17.1mmHg, p=0.03)and the patients who suffered pneumonia was more frequent(55% vs. 28%, p=0.07)in F group than in S group. Conclusions; A high PCO2 value and suffering pneumonia were associated with unsuccessful NPPV treatment of the patients with AHF. 277 一般演題 ︵ポスター︶ Patients with atrial fibrillation(AF)and heart failure are at high risk for left atrial thrombus formation, though thrombi in right atrium are rare. The 62-years-old man was admitted with acute decompensated heart failure( ADHF)caused by AF with rapid ventricular response( 180beats/min). He underwent pulmonary vein isolation(PVI)at 48-yearsold after four episodes of heart failure admission with AF. After PVI, he developed no clinically documented AF. On admission, left ventricular wall motion was disturbed with ejection fraction of 30% and left ventricular was enlarged. He was treated with furosemide, carperitide and intravenous heparin under countinuous positive airway pressure. Intravenous amiodarone was used for the rate control as HR was resistant to digitalis. On the third hospital day, a 3 × 4 cm mobile thrombus was found in right atrium on follow-up echocardiography. Contrast enhanced CT showed multiple pulmonary embolism. Emergency operation was performed to remove the thrombi in pulmonary artery and right atrium. Long thrombus from right atrium to inferior vena cava over 10cm was found and successfully removed. He discharged on the 23th hospital day with good postoperative course. Cardiovascular Division, Osaka Police Hospital, Osaka, Japan、 Cardiovascular Division, Higashiosaka City General Hospital, Osaka, Japan 1) 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 ポスター16(P16)虚血性心疾患による心不全 P-079 P-081 A Case of Heart Failure and Coronary Spasm 1) 1) 1) Hiroki TERAGAWA 、Yuichi FUJII 、Tomohiro UEDA 、 Shuichi NOMURA2) DepartmentofCardiovascularMedicine,HiroshimaGeneralHospitalof West Japan Railway Company、 2)Department of General Physician, HiroshimaGeneralHospitalofWestJapanRailwayCompany 1) 一般演題 ︵ポスター︶ As the cause of heart failure, there are several cardiac disorders. Coronary spasm, which causes vasoconstriction of epicardial coronary arteries, leading to myocardial ischemia. Recently, it has been reported that coronary spam causes heart failure. We also experienced a case of heart failure and coronary spasm. A 69-year-old woman was admitted for further examination and treatment of chest pain. Emergency cardiac catheterization showed no significant stenosis on coronary angiograms, but on a left ventriculogram, diffuse wall hypokinesis was observed. After treating heart failure, cardiac catheterization was performed again. A spasm provocation test showed coronary spasm of the right and left coronary arteries. Under taking vasodilators and standard treatment for heart failure, she had experienced no readmission. Coronary spasm should be considered as one of causes of heart failure. Impact of Infarct Location on Development of Ischemic Mitral Regurgitation in Patients with Acute Myocardial Infarction Kitae KIM、Shuichiro KAJI、Takeshi KITAI、Tomoko TANI、 Makoto KINOSHITA、Natsuhiko EHARA、Atsushi KOBORI、 Yasuhiro SASAKI、Toru KITA、Yutaka FURUKAWA Department of Cardiovascular Medicine, Kobe City Medical Center GeneralHospital Background: It has been reported that patients with inferior myocardial infarction(MI)have higher incidence of ischemic mitral regurgitation(IMR)compared with patients with anterior MI. However, the impact of infarct location on development of IMR after acute MI during long-term follow-up period has not been fully investigated. Methods and Results: We studied 652 consecutive patients with acute MI from 2000 to 2008 who underwent emergent coronary angiography and transthoracic echocardiography during index hospitalization. The mean age was 65±11 years and 509 patients(78%)were men. A total of 44 patients had combined anterior and infero-posterior(Ant+IP)infarct locations(Ant+IP-MI group)including prior MI(n=37)or second MI during follow-up( n=7). The remaining 610 patients had isolated anterior(n=271; Ant-MI group)or infero-posterior MI(n=337; IP-MI group)location. At late follow-up echocardiography, the incidence of significant IMR(moderate or severe)was significantly higher in Ant+IP-MI group, compared to Ant-MI group and IP-MI group (36% vs. 6% vs. 10%, P<0.001). Cox proportional model revealed that combined Ant+IP infarct locations was associated with a significant increase in the risk of heart failure independent of age, gender, and baseline IMR.Conclusions: Combined Ant+IP infarct location, which was associated with increased risk of heart failure, was an independent predictor of late IMR development in patients after acute MI. P-080 P-082 Endothelial Function is Associated with Ventilatory Efficiency Rather Than Exercise Tolerance in Patients after Acute Myocardial Infarction Effect of Left Ventricular Ejection Fraction on 2-Year Clinical Cutcomes in Patients with Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention with Drug-Eluting Stents Etsushi KYUNO1)、Yoshitaka ISO2)、Naoko IKEDA1)、 Chisato SATO2)、Hideyuki MAEZAWA1)、Hiroshi SUZUKI2) Woong JEON1)、Sang-Ho PARK1)、Seung-Woon RHA2)、Kanhaiya L. PODDAR2)、 Meera KUMARI2)、Yun Kyung KIM2)、Jin Oh NA2)、Cheol Ung CHOI2)、Hong Euy LIM2)、 Jin Won KIM2)、Eung Ju KIM2)、Chang Gyu PARK2)、Hong Seog SEO2)、Dong Joo OH2) Division of Cardiology, Showa University Fujigaoka Rehabilitation Hospital、2)DivisionofCardiology,ShowaUniversityFujigaokaHospital 1) Ventilatory efficiency assessed by cardiopulmonary exercise testing(CPX)predicts prognosis of heart failure patients. Aim of this study was to investigate the cross-sectional association between exercise capacity, ventilatory efficiency and endothelial function determined by flow-mediated dilation(FMD)in patients with lower exercise capacity after acute myocardial infarction (MI).Methods and Results: We studied 20 acute-MI patients with low exercise capacity(peak oxygen consumption(VO2)<16 ml/ min/kg). FMD and CPX were performed in sub-acute phase of the MI. The %FMD were inversely and significantly correlated with the VE/VCO2 slope(r= − 0.44, p<0.05)but not associated with the VO2 levels at anaerobic threshold and peak. The patients were divided by VE/VCO2 slope value at 35(>35, n=7; <35, n= 13). %FMD was significantly lower in the patients with VE/VCO2 slope >35 than in the patients with<35, whereas there were no significant differences between the two groups in peak VO2 levels, plasma BNP concentration, ejection fraction documented by echocardiography and the clinical characteristics. Conclusion: Results of the present study demonstrated that FMD was associated with ventilatory efficiency rather than exercise tolerance in acute MI patients. FMD may reflect and stratify the severity in in the lower exercise capacity patients after acute MI. 278 Cardiology Department, Soonchunhyang university cheonan hospital, cheonan, Korea、 2)Cardiovascular Center, Korea University Guro Hospital,Seoul,Korea 1) Background: The purpose of this study is to evaluate the effect of left ventricular ejection fraction(LVEF)on clinical outcomes in patients with acute myocardial infarction(AMI) Methods: A total of 464 patients with AMI undergoing primary percutaneous coronary intervention between 2004 to 2009 were enrolled. They were divided into two group; LVEF 40%(n=279)and LVEF<40%(n=185). The clinical follow-up end-point was total major adverse cardiac event (MACE)including death, AMI, TVR, Non-TVR Results: At 2-year(follow-up, 89.2%), major clinical outcomes was similar to two groups except total MACE and cardiac death. However, when in-hospital mortality was excluded, total MACE and cardiac death were also similar to two groups(table, figure). Conclusions: LVEF is associated with inhospital cardiac death and total MACE. However, LVEF doesn t seem to be independent predictor for a major clinical outcomes except in-hospital period. プログラム・抄録集 ポスター17(P17)様々な角度から心不全を考える P-083 P-085 Design Challenges for Heart Failure Prevention Clinical Trials: Adaptive Design Approach Hae-Young LEE、Wook-Jin CHUNG、Hui-Kyung JEON、 Hong-Seog SEO、Dong-Ju CHOI、Eun-Seok JEON、Jae-Joong KIM、 Joon Han SHIN、Seok-Min KANG、Sung Cil LIM、Sang-Hong BAEK Toshimitsu HAMASAKI1,2)、 Atsushi NAKANO3)、Kanae TAKAHASHI1)、Hideaki KANZAKI4)、 Masanori ASAKURA3)、Masafumi KITAKAZE3) Seoul National University Hospital、2)Gachon University Gill Hospital、 CatholicUniversityUijeongbuSt.Mary'sHospital、4)KoreaUniversityGuro Hospital、5)SeoulNationalUniversityBundanghospital、6)SamsungMedical Center、7)Asan Medical Center、8)Ajou University Hospital、9)Severance hospital of Yonsei University、10)Catholic College of Pharmacy, Catholic UniversityofKorea、11)CatholicUniversitySeoulSt.Mary'sHospital 1) Objectives. The association between the coding region variations of adrenergic receptor signaling genes and therapeutic effect were investigated in heart failure patients. Methods. Genotypic analysis was carried out in 83 patients of chronic heart failure patients(NYHA class II-III)with reduced left ventricular ejection fraction(LVEF)< 45%. Enrolled patients started bisoprolol 1.25mg once daily, up-titrated to the maximally tolerable dose, then maintained until 1 year of treatment. Results. 1)At position 389 of the beta-1 adrenergic receptor(ADRB1), the observed minor Gly allele frequency was 21% and no deviation from Hardy-Weinberg equilibrium was seen in the genotypic distribution of Arg389Gly(p=0.75). 2)There was no significant difference in the final heart rate across the genotypes. However, Arg389Arg genotype group required significantly larger amount of bisoprolol compared with Gly389X(Gly389Arg+Gly389Gly)group in order to achieve the same level of heart rate reduction(5.26±2.62 mg vs 3.96±2.05mg, p=0.022). 3)There were no significant differences either in LVEF or in left ventricular enddiastolic volume between Arg389Arg genotype group and Gly389X group. There was also no significant difference in exercise capacity or B-natriuretic peptide level change between two groups. 4)However, interestingly, there was two-fold higher rate of readmission(21.2% vs 10.0%, p=0.162)and one heart-failure related death in Arg389Arg group. Conclusion: In heart failure patients, ABRB1 Gly389X genotype showed greater response to bisoprolol than Arg389Arg genotype. ABRB1 Gly389X genotype was also suggested to have better prognosis than Arg389Arg genotype. The findings of this study implicate the potential of individually tailoring of beta-blocker therapy according to genotypes. Cardiovascular prevention clinical trials generally require a large number of subjects and long-term follow-up period to observe events of interest to evaluate the risk and benefit of a test intervention compared with any control intervention. These may increase difficulties in conducting and managing clinical trials with respect to resources such as time and cost.One recent major advance in clinical trial methodology is adaptive designs. Adaptive designs allow for smaller, shorter trials while ensuring scienti¬fic rigor and integrity of results. Adaptive designs offer the opportunities of saving resources and preventing subjects from being exposed to an ineffective intervention unnecessarily. However, along with these benefits, adaptive designs introduce additional challenges: decision complexity, statistical expertise and operational demands. Accumulated experiences are required for a practical use of adaptive designs for clinical trials, especially for cardiovascular prevention clinical trials.In this presentation, we will share our lessons learned in planning and designing "linical Study of the Effect of Teneligliptin on the Left Ventricular Diastolic Dysfunction in Patients with Type 2 Diabetes Mellitus"(TOPLEVEL Study). As adaptive features, the study design allows to assess either futility or efficacy of the test intervention, and to recalculate the sample size based on the observed effect at the interim. We discuss the advantages and disadvantages of adaptive designs in heart failure prevention clinical trials. 1) 3) Department of Advanced Medical Technology Development, National CerebralandCardiovascularCenter、2)DepartmentofInnovativeClinical TrialsandDataScience,OsakaUniversityGraduateSchoolofMedicine、 3) Department of Clinical Medicine and Development, National Cerebral and Cardiovascular Center、4)Department of Cardiovascular Medicine, NationalCerebralandCardiovascularCenter P-084 Webメールを用いた登録割付システムの適用 高橋 佳苗、濱崎 俊光 国立循環器病研究センター 先進医療・治験推進部 臨床試験において,確率化操作は,患者特性に関わる偏りが 治療効果の比較に及ぼす影響をできるだけ小さくし,治療の 比較可能性を高めるための唯一で最良の方法である.実地に おいては,妥当な方法と手段をもって,適切な体制のもとで 確率化操作を実行することが必須であるが,予算の限られた 医師主導臨床試験では,これらのすべてを満たす環境を準備 することが困難な場合がある.国立循環器病研究センターで は,Web メールを介して被験者登録・割付が行えるシステム を開発し,研究実施者が比較的容易に,被験者登録と確率化 操作が実行できる環境を整備した.本システムは,オペレー タなどの人を介さず Web メールにて被験者登録・割付を 24 時間,提供するものである.各試験の情報、割付登録票・結 果票を Microsoft Excel と Adobe Acrobat を用いて定義する のみでよく,システムの試験毎の仕様変更は必要としない. 本発表では,今回開発した登録割付システムを,循環器疾患 を対象とした実際の臨床試験に適用した事例を紹介し,適用 から得られた経験や知識を共有することを目的とする. P-086 Long-Term Prognosis in Patients Treated with Cardiac Resynchronization Therapy Reisuke YOSHIZAWA1)、Tomonori ITOH1)、Yoshihiro SATOH2)、 Satoshi NAKAJIMA1)、Mahito OZAWA2)、Fusanori KUNUGITA2)、 Takashi KOMATSU2)、Motoyuki NAKAMURA2)、Yoshihiro MORINO1) DivisionofCardiology,DepartmentofInternalMedicine,IwateMedical University School of Medicine, Morioka, Japan、 2) Division of Cardioangiology,NephrologyandEndocrinology,DepartmentofInternal Medicine,IwateMedicalUniversitySchoolofMedicine,Morioka,Japan 1) Background: The effect of cardiac resynchronization therapy(CRT)is controversial for long-term prognosis in patients with severe heart failure in the previous study. Objectives: To clarify long-term prognosis in patients treated with CRT. Methods: The subjects were 24 consecutive CRT patients admitted to our institute from 2006 to 2014(21 males and 3 females). We retrospectively evaluated patient characteristics and electrocardiogram just before and after CRT implanted. Cardiac events were defined as heart failure requiring hospitalization/death from cardiovascular events. Results: Average age at CRT implantation was 60±14 years in the study patients. Basal heart disease were as follows: dilated cardiomyopathy 15, ischemic heart disease 3, and the others 6. Average BNP level before CRT implantation decreased to after CRT implantation(820±676 pg/ml to 587 ±771 pg/ml; p=0.206). However, QRS widths just before and after CRT implantation were 150±27 and 146±22 msec respectively(p=0.601).2 cases required intra-aortic balloon pump just before CRT implantation.Long-term prognosis of an average observation period of 35 months yielded: death 10 cases,(7 cardiac and 3 non-cardiac deaths;mortality rate 42%).Readmission rate caused by heart failure after CRT implantation was 58%(14 cases). Conclusion: Readmission rate after CRT implantation was high and longterm prognosis was low. Not only CRT implantation but also fundamental and polite care in patients with severe heart failure is needed. 279 一般演題 ︵ポスター︶ Impact of the Beta-1 Adrenergic Receptor Polymorphism on Tolerability and Efficacy of Bisoprolol Therapy in Heart Failure Patients 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 ポスター18(P18)様々な心筋症を診る P-087 P-089 A Novel Hemodynamic Subsets in the Predicting of Need for Inotropic Support in Heart Failure A Case of Woman with Fabry Disease Whose Myocardial Hypertrophy May Become Worse by Changing Enzyme Replacement Therapy Muneyoshi TANIMURA1)、Kaoru DOHI1)、Naoki FUJIMOTO2)、 Tetsusiro TAKEUCHI1)、Yuichi SATO1)、Naoto KUMAGAI1)、Shiro NAKAMORI1)、 Norikazu YAMADA1)、Mashio NAKAMURA3)、Masaaki ITO1) Yasuhiro MORITA、Hideyuki TSUBOI、Itsurou MORISHIMA、 Michitaka UESUGI、Yousuke INOUE、Ruka YOSHIDA Department of Cardiology and Nephrology, Mie University Graduate School of Medicine、 2) Department of Molecular and Laboratory Medicine,MieUniversityGraduateSchoolofMedicine、3)Departmentof Clinical Cardiovascular Research, Mie University Graduate School of Medicine Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme α-galactosidase. A 56 years old woman was referred to our hospital with respiratory discomfort at April 2005. She was already diagnosed with Fabry disease in our hospital. Echocardiogram showed a thickening of the interventricular septum(23mm), and BNP was raised(363.9pg/dl). We started enzyme replacement therapy by using agalsidaseβ. 6 months later, her symptom was vanished and IVST was decreased significantly(13mm). In September 2011, we switched enzyme to agalsidase-α, because of shortage of agalsidase-β. 1 year later, echocardiogram showed a thickening of the interventricular septum again(18mm)and increase in brightness. MRI showed late enhancement in septum. We switched enzyme from agalsidase-α to agalsidase-β again. Agalsidase-β and α considered to be almost equal. But in this case, enzyme efficacy may not be equal. 1) 一般演題 ︵ポスター︶ PurposeWe aimed to elucidate the best hemodynamic parameter to predict need for inotropic support in patients with heart failure(HF).MethodsWe retrospectively evaluated 177 HF patients(65±16 years old, 125 males, NYHA classes I/II/II/IV were 27/78/55/17)who underwent right heart catheterization(RHC)on hospital admission.ResultsFifteen(8.5%)patients required inotropic support during hospitalization. Among various hemodynamic variables, the combination of left ventricular stroke work index(LVSWI: cutoff value of 32.2g/m2/beat)and mean right atrial pressure (mRAP: cutoff value of 12mmHg)had the greatest ability for predicting need for inotropic support with sensitivity of 93% and specificity of 91% (Figure).ConclusionThe novel hemodynamic subsets based on combined RHC-derived LVSWI and mRAP have the greatest utility in predicting need for inotropic support in HF. P-088 An Assessment of the Current Status on the Palliative Care in Patients with End-of-life Stage Heart Failure Machiko ASAKA、Norihiko KOTOOKA、Koichi NODE DepartmentofCardiovascularMedicine,SagaUniversity,Saga,Japan According to the recommendations and guidelines for palliative care in end-stage heart failure, the health-care professionals should inform patients and their family about prognosis, life-prolonging procedures and the role of the palliative care and the hospice program. However, very few patients have discussed about their wishes for medical care at the end-of-life in advance. There still remain a lot of issues to be resolved about palliative care in end-stage heart failure.Of the 1044 patients with heart failure who admitted in our hospital between April 2010 to July 2013, 68 patients died. We investigated the medical records of these 68 deceased patients retrospectively. Of the 68 patients, 36 patients were hospitalized due to acute heart failure that includes acute myocardial infarction, and 32 patients were due to acute exacerbation of chronic heart failure. Of the 32 patients with chronic heart failure, 19 patients were readmission.The only one patient was informed his prognosis and confirmed his willingness of future medical treatment at the end-of-life in advance, and 4 patients were received palliative care including continuous subcutaneous infusion of morphine in collaboration with palliative care team.We need to consider questions about palliative care for patients with end-stage heart failure, including optimal timing of initiation, preferable team, opioid administration, willingness of life prolonging therapy, and resuscitation. 280 DepartmentofCardiology,OgakiMunicipalHospital P-090 A Case of Dilated Cardiomyopathy with Functional Recovery along with The Disappearmnace of Electrical Dyssynchrony on Response to Pharmacotherapy Yuichiro IIDA、Takayuki INOMATA、Teppei FUJITA、 Yuki IKEDA、Takeru NABETA、Shunsuke ISHI、Takashi NARUKE、 Hisahito SHINAGAWA、Toshimi KOITABASHI、Jyunya AKO The Department of Cardiovasucular Medicine, University of Kitasato, Kanagawa,Japan A 70-year-old male was diagnosed and treated as non-ischemic dilated cardiomyopathy(DCM)with complete left bundle branch block(CLBBB).We observed him during 5 years after administration of anti-neurohumoral agents such as carvedilol and enalapril. There was no significant improvement in LVEF or changes in QRS formation during the first 3 years. He had stably mild heart failure(HF)complaints of NYHA class II and no re-hospitalization. However, CLBBB improved to normally narrow QRS at 3 years later and subsequent LVEF at 4 years later was improved to a normal rage of LVEF 66 %. We evaluated his electrocardiographic findings. There is no significant change in PQ interval, QRS duration, and other clinical data, whereas only QTc interval was gradually shortened prior to the recovery to normal QRS formation. There are few reports concerning time course of electrocardiographic findings in DCM. From this case we experienced an electrical normalization from CLBBB after only medical treatments. Moreover, shortening of QTc interval was the earliest finding among electrocardiographic parameters. QTc interval may be a surrogate marker of the electrical reverse remodeling, then predict prognosis of DCM. プログラム・抄録集 P-091 P-093 A Case of Human Immunodeficiency VirusRelated Heart Failure Accompanied with High Cardiac-output A Case of Refractory Anthracycline Induced Cardiomyopathy Worsened by Septic Embolism Due to Extremely Rare Mycosis Megumi YAMAMURO、Noriaki TABATA、Seigo SUGIYAMA、 Koichi KAIKITA、Seiji HOKIMOTO、Hisao OGAWA Takahide KODAMA、Yasuhiro TOMITA、Minoru OONO Departments of Cardiovascular Medicine, Graduate School of Medical Sciences,KumamotoUniversity A 29-year-old woman with very rare Ewing sarcoma originating from liver developed heart failure due to chemotherapy including anthracycline antibiotics. The first symptom was dyspnea(NYHA class 3)and screening tests revealed severe pleural effusion and deteriorated ejection fraction(19%)with dilated left-ventricularend-diastolic diameter(59mm). Moreover her mental state was depressive and she rejected invasive monitoring and central venous catheter(CV)insertion. First of all 3 microgram/kg/min of dobutamine and 0.0125 microgram/kg/min of hANP were administered, however, her symptoms worsened. Additional diuretic agents, flosemide and tolvaptan, and inotrope, milrinone, were administered through CV and the heart failure was managed. Through introduction of carvedirol(up to 5mg), she claimed malaise, low-grade fever and bloody phlegm and the decompensated heart failure relapsed. A chest plane CT was carried out and it revealed multiple nodules in bilateral lung field. The diagnosis was septic embolism or metastasis of malignant tumor. We believed the diagnosis of septic embolism because there was long-term detained CV catheter in her right jugular vein. Therefore, we performed blood culture from 3 different accessible site and all of the 3 blood cultures showed extremely rare mycosis, Paecilomyces lilacinus infection. In accordance with the result of the blood culture, we administered 200mg of voriconazole for her and her symptoms were gradually getting better and reduced dobutamine intravenous infusion. P-092 Heart Failure without Subjective Skeletal Muscle Weakness in Becker Muscular Dystrophy Patient: A Case Report Toshiyuki OHYA1)、Mahoto KATO1)、Kazuhito TOHYAMA1)、Yasuo OKUMURA1)、 Tadateru TAKAYAMA1)、Ichiro WATANABE1)、Takafumi HIRO1)、 Tsutomu YAMADA3)、Tomoko YAMAMOTO2)、Atsushi HIRAYAMA1) 1) Division of Cardiology, Department of Internal Medicine, Nihon UniversitySchoolofMedicine,Tokyo,Japan、2)DepartmentofPathology, Tokyo Women's Medical Univerisity, Tokyo, Japan、 3) Division of Pathology, Department of Pathology, Nihon University School of Medicine,Tokyo,Japan We describe a case of Becker Mascular Dystrophy(BMD)in a 42 year-old man without subjective skeletal muscle weakness showed lower left ventricular systolic function in echocardiography. He visited our outpatient clinic with slight fatigue in legs. His serum creatine kinase level was elevated(2000 to 5000 IU/l).Psuedohypertrophy was obserbed in both crural muscles but Manual Muscle Testing showed normal skeletal muscle powers in Legs. Echocardiography data showed reduced ejection fraction(40%)and dilated left ventricular diastolic diameter(56mm). Magnetic resonance imaging showed a liner Late Gadolinium Enhancement image in the middle myocardial layer in left ventricle lateral wall. Coronary angiography showed normal coronary arteries. Endomyocardial biopsy was performed and pathological data is not a typical BMD pattern including antiDystophin staining of immunohistochemistry. Genetic testing (Multiplex ligation-dependent probe amplification)was demonstrated. The deletion of only 4th Exon of Dystrophin gene was detected. We diagnosed his heart failure caused by insufficient dystophin function due to BMD. We suggested only one exon skipping may produce specific myocardial dysfunction without crural muscle dysfunction and typical change in immunohistochemistry of dystrophin staining. 281 一般演題 ︵ポスター︶ Heart failure associated with human immunodeficiency virus( HIV)has been recognized early in the epidemic. HIV-associated myocarditis, nutrition-deficiencies including selenium, drugs-cardiotoxicity, and inflammatory cytokinemia have been suggested as possible causes; however, the precise etiology remains unresolved. We here report on a man of heart failure with HIV infection. He did not have any of the causes above; but did have high cardiacoutput despite low systolic function. After anti-retroviral therapy, his systolic function was improved, interestingly with an inverse reduction and normalization of cardiacoutput. Our case indicated that high cardiac-output might be involved in pathogenic mechanisms of HIV-related heart failure. CardiovascularCenter,ToranomonHospital 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 ポスター19(P19)補助循環を用いた心不全治療 P-094 P-096 A Case of Cardiogenic Shock Treated with Paracorporeal Left Ventricular Assisted Device Caused by Acute Myocardial Infarction Impact of MELD Score on Outcome in Patients with Percutaneous Extracorporeal Membrane Oxygenation Followed by Ventricular Assist Device Implantation Kensuke HIRASAWA1)、Yu HATANO1)、Taro SASAOKA1)、 Toshiharu YOSHIKAWA1)、Yasuhiro MAESHIMA1)、Masahiko GOYA1)、 Takashi ASHIKAGA1)、Kenzo HIRAO1)、Hirokuni ARAI2)、Mitsuaki ISOBE1) Osamu SEGUCHI1)、Tomoyuki FUJITA2)、Takuma SATO1)、 Haruki SUNAMI1)、Masanobu YANASE1)、Hiroki HATA2)、 Takeshi NAKATANI1) DepartmentofCardiology,TokyoMedicalAndDentalUniversity,Tokyo, Japan、2)Department of Cardiovascular Surgery, Tokyo Medical And DentalUniversity,Tokyo,Japan Department of Transplantation, National Cerebral and Cardiovascular Center,Osaka,Japan、2)DepartmentofAdultCardiacSurgery,National CerebralandCardiovascularCenter,Osaka,Japan 1) 一般演題 ︵ポスター︶ Case: A 42-years-old man was suffered from chest pain and transferred to our hospital with cardiogenic shock. Under intraaortic balloon pumping (IABP)support, emergency coronary angiography was performed. Left anterior descending(LAD)and left circumflex branch(LCX)were chronic total occlusion, and right coronary artery(RCA)was total thrombotic occlusion. Percutaneous coronary intervention( PCI)was performed on RCA. However, cardiogenic shock was sustained and incessant ventricular tachycardia was occurred. Percutaneous cardiopulmonary support(PCPS)and mechanical ventilation were performed. After PCI, left ventricular function was severely impaired and aortic valve was continuously closed under PCPS. It is difficult to remove mechanical support, coronary artery bypass grafting and paracorporeal left ventricular assist device were performed for bridge to candidacy the next day after the onset. After registration of heart transplantation, implantable left ventricular assisted device was implanted 30 days after the onset.In Japan, implantable left ventricular assisted device is adopted to patients with severe heart failure waiting for heart transplantation. This case suggests that using paracorporeal left ventricular assist device for bridge to candidacy might be effective to severe acute heart failure caused by acute myocardial infarction depending on mechanical support. P-095 Purpose Recently, models for end-stage liver disease( MELD)score hase reported to be a prognostic factor in patients with heart failure. In this study, we aimed to elucidate the prognostic values of MELD score in patients with severe hemodynamic instability supported by percutaneousextracorporeal membrane oxygenation(p-ECMO), who underwent sequential ventricular assist device(VAD)implantation as bridge to bridge therapy. Methods We retrospectively reviewed consecutive 131 patients who underwent VAD implantation between 2001 and 2013. Thirteen patients(mean age 32.6±11.1 years, 20 males)who received p-ECMO insertion prior to VAD implantation were analyzed in more detail from their clinical characteristics and they were stratefied according to their MELD-exclude INR(MELD-XI)score that were calculated just before VAD implantation. Results All 30 patients survived at least 2 weeks after VAD implantation. The mean MELD-XI score was 18.8±7.1. Univariate cox proportional hazard model demonstrated that increasing MELDXI score significantly predicts poor prognosis during VAD support period (hazard ratio, 1.08; 95% confidence interval, 1.01-1.16; p=0.02). Kaplan-Meier analysis revealed that a MELD-XI score>17 was a strong predictor of mortality during VAD support period(p=0.008, log-rank test). Conclusion End-organ function assessed by MELD-XI score has potential to predict the prognosis in patients with p-ECMO who are scheduled to receive VAD implantation. P-097 Importance of Aortic Valve Opening under Percutaneous Cardiopulmonary Support(PCPS)in Patients with Fulminant Myocarditis; from the 2 Distinctive Cases 1) 2) 2) Masao YAMAGUCHI 、Taro SASAOKA 、Kensuke HIRASAWA 、 Mie SEYA2)、Syunji YOSHIKAWA2)、Yasuhiro MAEJIMA2)、 Masahiko GOYA2)、Takashi ASHIKAGA2)、Kenzo HIRAO2)、Mitsuaki ISOBE2) Soka Municipal Hospital、 2)Tokyo Medical and Dental University DepartmentofCardiovascularMedicine 1) Case 1: A 48-year-old male, who was diagnosed as fulminant myocarditis was transferred to the intensive-care unit in our hospital. Echocardiography showed progressive decline of left ventricular function after admission. The 2nd day, intraaortic balloon pumping (IABP)and PCPS were introduced due to cardiogenic shock. Under cardiopulmonary support, we paid careful attention to keeping aortic valve open in systole to prevent thromboembolic complications. After 10 days of cardiopulmonary support, his cardiac function improved gradually and he weaned from IABP and PCPS. He discharged on foot without major complications. Case 2: A 44-year-old female with fulminant myocarditis under PCPS was transferred to our hospital in consideration of left ventricular assist device(LVAD). Her echocardiography showed continuous closure of the aortic valve and spontaneous echo contrast in left ventricle. At the time of arrival at our hospital, major cerebral hemorrhagic infarction was found on brain CT. Lack of opening aortic valve under PCPS might induce thromboembolic complication. She died due to cerebral hernia 10 days later.Discussion: These cases imply that evaluation and retention of the aortic valve opening are important to avoid thromboembolic complications in patients with fulminant myocarditis. LVAD implantation could be beneficial in those cases who could not keep aortic valve open in systole under PCPS. 282 1) Impact of Implantable Ventricular Assist Devices on Long-Term Prognosis of Patients with Advanced Heart Failure Tatsuo AOKI1)、Koichiro SUGIMURA1)、Kotaro NOCHIOKA1)、 Shunsuke TATEBE1)、Saori YAMAMOTO1)、Masanobu MIURA1)、Kimio SATO1)、 Masatoshi AKIYAMA2)、Yoshikatsu SAIKI2)、Hiroaki SHIMOKAWA1) 1) Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine、2)Department of Cardiovascular Surgery, Tohoku UniversityGraduateSchoolofMedicine Backgrounds: Implantable ventricular assist devices (VADs)became available in 2011 and may have changed the prognosis of advanced heart failure( HF)patients in Japan. Methods and Results: We retrospectively identified 40 adult patients with advanced HF(mean age, 43.6 years; male, 30(74 %))with the VADs indication in our hospital from 2004 to 2013. We categorized them into 4 groups according to the INTERMACS profile(profile 1 or not)and hospitalization date(before or after April 2011). KaplanMeier survival curves showed that the patients with profile 1 after 2011 tended to have a lower mortality compared with those before 2011 ( P = 0 . 1 3 )( F i g u r e ). Conclusions: Implantable VADs tended to improve long-term prognosis even in advanced HF patients with INTERMACS profile 1, although further studies with a larger number of patients are needed. プログラム・抄録集 ポスター20(P20)心リモデリングを抑制する P-098 Hemodynamic Differences Between Axial and Centrifugal-Flow Pumps: Which Type of Left Ventricular Assist Device Should be Selected for Each Patient? Seiko NAKAJIMA1)、Osamu SEGUCHI1)、Haruki SUNAMI1)、 Takuma SATO1)、Yoshihiro MURATA1)、Hiroki HATA2)、 Tomoyuki FUJITA2)、Masanobu YANASE1)、Takeshi NAKATANI1) P-099 Ketone Body Metabolism Attenuates Oxidative Stress and Cardiac Remodeling in Pressure Overload Heart Failure Motoki UCHIHASHI、Atsushi HOSHINO、Makoto ARIYOSHI、 Shuhei TATEISHI、Kazunori ONO、Satoshi KAIMOTO、 Kuniyoshi FUKAI、Eri KANAI、Satoaki MATOBA Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine,Kyoto,Japan Background Two types of implantable continuous-flow left ventricular assist device(LVAD), axial and centrifugal-flow LVAD, have been available for advanced heart failure patients and they have different pump physiology. However, detail hemodynamic characteristics of both pumps in human are not well elucidated. Methods & Results We retrospectively reviewed consecutive 29 patients( mean age 41.0 ± 11.5)who received continuous-flow LVAD implantation between 2011 and 2014(20 patients with HeartMateII, A group and 14 patients with EvaHeart, C group). Clinical measurements and hemodynamic parameters after LVAD implantation were compared between 2 groups. Although there was no significant difference in cardiac index, left ventricular diastolic dimension, right atrial pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, and right ventricular stroke work index were significantly lower in A group(54.3±13.3 vs 69.2±12.4 mm: p=0.013, 3.7±2.9 vs 5.8±2.5 mmHg: p=0.039, 13.6±3.3 vs 19.3±5.0 mmHg: p=0.0034, 3.2±2.4 vs 8.2± 3.6 mmHg: p<0.001, 4.3±1.9 vs 6.4±1.8 g/m2: p=0.011, respectively). Clinically, no patient has developed persistent right heart failure(RHF)or other hemodynamic deterioration.Conclusion Patients with axial-flow pump showed significantly smaller LV size and lower intracardiac pressure early after implantation. They might get through RHF in the early phase, but impact on late phase RVF and appropriate pump selection are the subjects of future investigation. Background: The shift of energy substrate from fatty acid to glucose accompanied by myocardial energy compromise is the hallmark of metabolic remodeling in pathological cardiac hypertrophy. However, it has not been investigated the pathogenic contribution of ketone body metabolism in heart failure. Methods and results: Pressure overload heart failure was introduced with the transverse aortic constriction(TAC). Microarray and mitochondrial iTRAQ proteomics revealed that the expression of Bdh1, an enzyme that catalyzes the NAD+/NADH coupled interconversion of acetoacetate and betahydroxybutyrate(betaOHB), was increased 2.5-fold in TAC-operated heart. Ketone body oxidation determined by measuring 14CO2 released from [1-14C] betaOHB in the isolated perfused hearts was upregulated 1.8-fold in TACoperated heart. To investigate the functional significance of increased ketone body oxidation we generated heart-specific Bdh1 Tg mice which had 1.7-fold increase of ketone body oxidation in the heart. When subjected to TAC operation Bdh1 Tg mice were resistant to cardiac hypertrophy, contractile dysfunction, and fibrosis. Immunochemical detection of carbonylated proteins demonstrated that protein oxidative damage was ameliorated in Bdh1 Tg mice. In vitro study with rat neonatal cardiomyocytes revealed that the adenovirus-mediated Bdh1 overexpression decreased ROS production and apoptosis. Conclusions: The present study demonstrates that ketone body oxidation is promoted in hypertrophied hearts. Increased ketone body utilization reduces oxidative stress and protects against heart failure progression after chronic pressure overload. Department of Transplantation, National Cerebral and Cardiovascular Center, Suita, Japan、2)Department of Adult Cardiac Surgery, National CerebralandCardiovascularCenter,Suita,Japan P-100 Identification of Novel Spliced Genes in Failing Heart Using Exon Array and RNASeq Shin ITO、Masanori ASAKURA、Kyung-Duk MIN、Miki IMAZU、 Kazuhiro SHINDO、Hiroki FUKUDA、Masafumi KITAKAZE C l i n i c a l R e s e a r c h a n d D e v e l o p m e n t , N a t i o n a l C e r e b r a l a n d CardiovascularCenter,Osaka,Japan The role of alternative splicing in heart diseases has not been completely elucidated. W aimed to perform a genomewide splicing analysis and develop a profiling of spliced genes in failing heart. We performed a comprehensive analysis of splicing genes, using both exon array and RNASeq. We constructed murine heart failure model induced by transverse aortic constriction for 8 weeks. We then extracted RNA from the hearts and analyzed it using the Mouse Exon 1.0 ST and Miseq V3 kit. Of 17,705 genes, exon array analysis identified 46 genes with significantly changes in the splicing pattern, but not in the gene expression level; 85 genes with changes in the splicing pattern and gene expression level(fold change >2, P<0.05). Furthermore, we confirmed the splicing events by RNA-Seq analysis: 5 genes(Mtus1, Arhgap25, Sfpi1, etc.)with changes only in the splicing pattern, and 19 genes(Rcan1, Rtn2, Synpo2l, etc.)with changes both in the splicing pattern and gene expression level. Of these 24 spliced genes, twenty-two genes have not been reported previously in heart diseases. Combined analysis using exon array and RNA-Seq is powerful tool to identify novel spliced genes in failing heart. Further study of the spliced genes identified in this study may reveal the pathophysiology of heart failure. 283 一般演題 ︵ポスター︶ 1) 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 P-101 P-103 一般演題 ︵ポスター︶ The Transition from Compensated Cardiac Hypertrophy to Failure Created by Transverse Aortic Constriction in Mice VEGF Overexpression and Right Ventricular Remodeling in Rats Exposed to Chronic Hypoxia Takaaki FURIHATA、Shintaro KINUGAWA、Arata FUKUSHIMA、 Tsuneaki HOMMA、Yoshihiro MASAKI、Shingo TAKADA、Tomoyasu KADOGUCHI、 Shouji MATSUSHIMA、Takashi YOKOTA、Hiroyuki TSUTSUI Mika MATSUI1)、Eiki WOO2)、Takahiro KATSUMATA2)、 Takehiro YAMAGUCHI3)、Minoru YOSHIYAMA3)、Yasukatsu IZUMI4)、 Atsuo NOMURA1)、Yuji FUJIWARA1)、Ryuji KATO1)、Tetsuya HAYASHI1) Department of Cardiovascular Medicine, Hokkaido University Graduate SchoolofMedicine,Sapporo,Japan LaboratoryofCardiovascularPharmacotherapyandToxicology,Osaka University of Pharmaceutical Sciences, Takatsuki, Japan、2)Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, Takatsuki,Japan、3)DepartmentofCardiovascularMedicine,OsakaCity UniversityGraduateSchoolofMedicine,Osaka,Japan、4)Departmentof Pharmacology, Osaka City University Graduate School of Medicine, Osaka,Japan Background: Transverse aortic constriction(TAC)operation is used as an experimental model of left ventricular(LV)hypertrophy and failure in mice. The severity of LV remodeling or failure may depend on the degree of TAC, but is variable among operated animals. Therefore, we tried to identify the optimal diameter of TAC to create this model with ease and high reproducibility.Methods and Results: To produce TAC in C57BL/6J mice(7-9 weeks, body weight 19-25g, n=110), a 7-0 nylon suture ligature was tightly tied around the transverse aorta against needles with 3 different diameters(mm). LV wall thickness, end-diastolic dimension and fractional shortening were measured by echocardiography.Conclusion: TAC with the diameter of 0.385mm can induce the transition from LV hypertrophy to failure in mice with relatively preserved survival. 1) Objective: Our previous study has shown that chronic hypoxia combined with vascular endothelial growth factor(VEGF)receptor blocker induces right ventricular (RV)remodeling in rats. The aim of this study was to examine the hypoxiainduced histological changes chronologically and evaluate the role of VEGF in the development of pulmonary arterial hypertension(PAH). Method: Male SpragueDawley rats were exposed to hypoxia(10% O 2)for 2 or 3 weeks, after a single subcutaneous injection of VEGF receptor blocker(Sugen 5416, 20 mg/kg, SU+Hypo group)or solution(V+Hypo group). They were then returned to normoxia for additional 10 weeks. After echocardiography, heart was examined by light and electron microscopy, immunohistochemistry, and RT-PCR. Results: After 2 weeks of hypoxia, tricuspid annular plane systolic excursion(TAPSE)and acceleration time/ ejection time(E/A)were decreased in SU+Hypo compared with those in V+Hypo (TAPSE, 2.25±0.26 vs. 3.03±0.04 mm; E/A, 0.22±0.07 vs. 0.32±0.03). Histologically, perivascular fibrosis and hypertrophy of cardiomyocytes and vascular smooth muscle cells were accelerated 10 weeks after the reoxygenation in SU+Hypo. Furthermore, delayed peak with overexpression of VEGF mRNA in RV myocardium was observed during hypoxia in SU+Hypo. Conclusion: Overexpression of VEGF at the timing of reoxygenation might be relevant to RV remodeling in the development of PAH. P-102 Intermittent Hypoxia Relevant to Sleep Apnea Increases Oxidative Stress and Accelerates Cardiac Remodeling in Cardiomyopathic Hamster Misaki MUROYA1)、Atsuo NOMURA1)、Ryuji KATO1)、Yoshio IJIRI1)、 Aiji SAKAMOTO2)、Takehiro YAMAGUCHI3)、Yasukatsu IZUMI4)、 Minoru YOSHIYAMA3)、Kazuhiko TANAKA2)、Tetsuya HAYASHI1) LaboratoryofCardiovascularPharmacotherapyandToxicology,Osaka University of Pharmaceutical Sciences, Takatsuki、 2)Laboratory of Vascular Biology, National Cerebral and Cardiovascular Center, Suita、 3) DepartmentofCardiovascularMedicine,OsakaCityUniversityGraduate School of Medicine, Osaka, Japan、 4)Department of Pharmacology, OsakaCityUniversityGraduateSchoolofMedicine,Osaka,Japan 1) Background: High prevalence rates of sleep apnea have been reported in patients with heart failure. The aim of this study was to investigate the effect of intermittent hypoxia on left ventricular(LV)myocardium and cardiac function in failing heart. Methods: Male Syrian(normal)and Bio14.6 cardiomyopathic hamsters(CM)at 20 to 24 weeks of age were exposed to intermittent hypoxia(IH: 5 minutes of 5% O2 followed by 5 min of 21% O2, repetitive for 8 h/day during daytime)or normoxia for 14 days. After evaluation of cardiac function by echocardiography, heart was examined by light and electron microscopy, immunohistochemistry, and RT-PCR. Results: In normal, IH tended to increase E/e'(26.6 vs. 17.6), but had no effect on LV ejection fraction(EF). In CM, IH also tended to increase E/e'(28.1 vs. 22.3),but decreased EF(34.2 vs. 44.5%). Histologically, IH increased cardiomyocyte diameter(19.9 vs. 17.4 μ m)and interstitial fibrosis(29.9 vs. 9.6%)in CM, compared with those of normal. Furthermore, IH increased oxidative stress such as 4-hydroxy-2nonenal proteins and c-fos mRNA expression. Conclusion: IH accelerated degeneration of cardiomyocytes and systolic dysfunction in CM, which might account for the poor prognosis of HF patients with sleep apnea. 284 P-104 The Role of Exosomes on Cardiac Hypertrophy Takehiro YAMAGUCHI1)、Yasukatsu IZUMI2)、 Takanori YAMAZAKI3)、Minoru YOSHIYAMA1) DepartmentofCardiovascularMedicine,OsakaCityUniversityMedical School, Osaka, Japan、 2)Department of Pharmacology, Osaka City University Medical School, Osaka, Japan、3)Department of Cardiology, AsakayamaGeneralHospital,Sakai,Japan 1) Objective: Sustained hypertension induces chronic inflammation, which causes cardiac remodeling and dysfunction. Exosomes are thought to contribute to intercellular communication. Here, we investigated the role of exosomes in experimental hypertensive models. Methods and Results: (1)Continuous infusion of angiotensin II(Ang II, 200 μg/kg/min)or a nitric oxide synthase inhibitor(N ω -nitro-L-arginine methyl ester; L-NAME, 1 mg/ mL in drinking water)induced hypertension and left ventricular hypertrophy. An amount of proteins in exosomes purified by ultracentrifugation from serum was increased in both hypertensive rats compared with that in normotensive rats. Addition of serum exosomes from hypertensive rats activated some signal transduction pathways such as JNK, p38MAPK, and Akt in human coronary arterial endothelial cells(HCAECs). Interestingly, the proteins in HCAECs were positive for CD68 antibody(a specific marker of macrophages) (2) . Human THP-1-derived macrophages were stimulated by Ang II(100 nM)or hypoxia, and purified exsosomes in culture media were treated to HCAECs. Activated macrophages increased an amount of exsosomal proteins and changed the constitutive proteins in medium exosomes. Medium exosomes collected in Ang II- and hypoxia-stimulated macrophages activated the same signal transduction pathways as the serum exosomes. These stimulations increased ICAM-1 in HCAECs, suggesting that stimulated THP-1-derived exosomes may induce proinflammatory effects and damage the endothelial cells.Conclusions: Endothelial damage by hypertension may be partially associated with activated macrophages-derived exosomes. プログラム・抄録集 ポスター21(P21)心不全再入院を減らすための試み P-105 P-107 再入院予防につながる心不全サポートチーム (HST)介入の一考察∼HST介入後再入院なく経 過している一例から∼ 1) 2) 3) 3) 中原 さちこ 、掛川 ちさと 、松川 龍一 、久保田 徹 、岡部 眞典 3) 1) 済生会福岡総合病院 看護部、2)済生会福岡総合病院 栄養部、3)済生会福 岡総合病院 循環器内科 P-106 妹尾 美和 1)、道城 綾 1)、多木 香織 1)、田頭 千賀子 1)、大坪 美保 1)、 萩原 敏恵 1)、萩倉 新 2)、後藤 賢治 2) 福山循環器病院 看護部、2)福山循環器病院 循環器内科 1) はじめに 近年チーム医療による患者教育の取り組みが行われ ている。当院では心不全パンフレットを用いた指導を実施し ていたが、セルフモニタリング不足による再入院となる患者 が多く、多職種協働による心不全チームの発足を機に従来の 指導内容・介入時期の変更を行った。今回、新たな介入方法 が心不全再入院や心不全死の抑制に有効であるか検討する。 方法 チームによる介入が開始された 2012 年 3 月前後 1 年の心 不全加療を要し生存退院が可能であった連続 317 名で検討。 既存介入群 199 例、新たな介入開始後のチーム介入群 118 例と し、それぞれの群での半年 の心不全再入院や心不全死 (以下 ; 心イベント)発生率の比較・評価を行った。結果・考察 半年 までの心イベントは既存介入群で 17%、チーム介入群で 20% に生じ Kaplan-Meier 曲線は有意差を認めなかった (logrank p=0.47) 。心不全手帳を用いたチーム介入には成功したものの 患者自身の危険予知能力向上には結びつかなかったと考えら れた。今後の課題として 「ヨーロッパ心不全セルフケア行動尺 度」 を用い行動変容を客観的に評価して心イベントの原因精査 と個々に応じた指導が必要である。 P-108 看護師による電話フォローアップは心不全の再入 院を予測できるか 重症心不全患者の再入院予防にむけた病棟−外来 の連携強化への取り組み 飯塚 裕美 1)、末永 祐哉 2)、高梨 久美 1)、平野 美樹 3)、斉藤 洋 4)、 鈴木 誠 2)、松村 昭彦 2)、橋本 裕二 2) 会田 絵理子 1)、篠原 佐和 1)、上村 敬子 1)、今村 光成 1)、増田 容子 1)、 岩崎 朋之 1)、大谷 朋仁 2)、坂田 泰史 2) 1) 亀田総合病院 CCU、2) 亀田総合病院 循環器内科、3) 亀田総合病院 HCU、4)亀田総合病院 リハビリテーション室 1) 大阪大学医学部附属病院 循環器内科病棟、CCU、2)大阪大学大学院 医学 系研究科 循環器内科学 【背景】退院後の看護師による電話インタビュー内容が心不全 の再入院を予測できるかは明らかにされていない。【目的】電 話インタビューで 90 日間の心不全患者の再入院を予測できる か明らかにする【方法】 2013.4 ∼ 2014.3 の期間に入院した心不 全患者を対象に、退院後30日以内に看護師による電話フォロー アップを行った。ESC ガイドラインで推奨されているセルフ ケアについてインタビューを行い、得られた回答をスコア化 し、90 日以内再入院群と非再入院群に分け比較した。【結果】 92 人 (76.3±12.7 歳、男性 48.9%)に、電話フォローアップを実 施。退院日から電話介入日までは11.9(7-16)日で、フォローアッ プ期間中に、医師へ報告 23 人(25%)、9 人(10%)が早期受診し、 14 人 (15.2%)が心不全で再入院した。しかし、各スコアは再 入院群と非再入院群間で有意差は得られず、また、電話イン タビューで得られたスコアは、90日間の再入院を予測しなかっ た (AUC:0.52 95% 信頼区間 :0.38-0.66)。【考察】心不全患者に 対して、いつ、どのように電話フォローアップをすべきか検 討していく必要がある。 【はじめに】 重症心不全患者の再入院率は約 20%と高く、再入院の予防に は病棟−外来看護師の連携が重要である。今回、この取り組 みにより再入院を予防できていると考えられる症例について 報告する。 【症例】 食事と塩分の摂取過多、過労、感冒を契機に年間 2 ∼ 3 回の 入院を 5 年間繰り返していた重症心不全の高齢女性。患者は 独居でキーパーソンは近所に在住の甥。 【看護の実際】 病棟看護師は、入院の契機となった増悪因子のアセスメント 結果に基づき計画的に介入を行ったが、退院後に実践出来て いるかを把握することは困難であった。 アドヒアランスの向上を目指した患者中心の看護という観点 から、外来看護師との連携強化として看護サマリでの情報共 有に加え、定例ミーティングで問題抽出を行い、対策として 新たに個別面談を導入した。導入前は、退院後短期間での入 院を繰り返すことが多く、入院期間も長期に及んだが、導入 後は 10 ヶ月以上再入院なく経過出来ている。 【結語】 病棟−外来看護師間で、看護目標ならびに計画を中心とした 情報共有やコミュニケーションの充実を図る事は、重症心不 全患者における再入院予防の一助になり得る可能性が示唆さ れた。 285 一般演題 ︵ポスター︶ 【目的】入退院を繰り返していた慢性心不全患者が心不全サ ポートチーム(以下 HST)介入後、再入院することなく経過し ている。この事例を振り返り有効であった HST の介入を考 察する。 【事例紹介】70 歳代、男性、無職。診断名 : 慢性心不全(EF19%、 AHA/ACC Stage 分類 C)、陳旧性心筋 塞、慢性腎臓病(Stage G4) 、糖尿病。20XX 年、慢性心不全増悪による入退院を繰り 返すようになり 6 ヶ月間で 4 回入院した。 【倫理的配慮】本研究について対象者へ説明を行い書面にて同 意を得た。 【介入の実際】20XX 年 4 回目の入院時から HST が介入。介入 の過程で体重増加・早期受診行動・塩分制限への認識と療養 行動に変化を認めた。また、HST メンバー以外のスタッフと も連携し抑うつ傾向や内服忘れに早期に対処した。最終入院 から 6 ヶ月後現在、心不全増悪による再入院なく経過してい る。 【考察】 HST の継続した介入により療養行動に変化を認めた。 また HST メンバー以外のスタッフとの連携もとれ、その結果、 心不全増悪因子となり得る事柄に早期に対処できた。これら が再入院予防に繋がっていると考える。今回は一例のみの考 察であり今後はデータを収集し HST 介入のアウトカムを明 確にすることが課題である。 心不全患者の再入院率軽減をめざして∼患者の行 動変容に向けての取り組み∼ 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 ポスター22(P22)心不全の様々なエビデンス P-109 尼崎病院における慢性心不全看護認定看護師によ る心不全看護外来の役割と課題 鷲田 幸一、佐藤 幸人 兵庫県立尼崎病院 看護部 慢性心不全看護認定看護師 一般演題 ︵ポスター︶ 【背景】心不全患者のセルフケアを長期に支援していく目的で 心不全看護外来を立ち上げた。【目的】尼崎病院における慢性 心不全看護認定看護師による心不全看護外来の特徴を分析し、 役割と課題を明確にする。【方法】後方的調査研究。カルテか ら心不全看護外来の介入を調査しその特徴を分析する。 【結果】 尼崎病院での心不全看護外来の特徴は以下。1. 患者面談の中で、 患者の語りから心不全知識の確認・心不全増悪因子の探索を 行う。2. 専門職種による患者教育後、断片的になっている患者 の知識を面談の中で整理・統合する。3. 心臓リハビリと連携を 取り、運動時の循環応答と身体負荷の関連性を患者と共有し、 自身の心臓を含めた身体への関心を高める。4. 患者面談により 得られた患者の認識や生活情報を病棟に伝達し、入院中の患 者教育の方向性を調整する。5. ソーシャルワーカー・退院調整 看護師と連携し退院調整を行う。【考察】尼崎病院における心 不全看護外来は、多職種と連携を図り、患者が心不全につい て考える機会を継続して提供することで、心不全のセルフケ アを支援する役割を果たしている。院内との多職種連携だけ でなく、今後は地域との連携強化が課題である。 P-110 心不全患者の早期再入院予防に向けた効果的な生 活指導の検討 大田 奈々、大工 真人、松田 直子、松田 麻未、熊本 紗千、殿谷 智子 富山県立中央病院 心不全患者は生活習慣病の増加や高齢化に伴い、さらなる 増加が予想されている。当病院の平成 25 年度における心不全 増悪に伴う年間の入院患者数は約 800 例前後、退院後 1 年以内 の再入院率は 41.6%となっており、看護師は心不全の一次予 防の必要性を理解し患者・家族に対して食生活や運動習慣、 アルコールや喫煙などの危険因子の是正に向けた教育を行う 役割がある。当病院においても、再入院予防が急務である。 また、当院の心不全加療退院後の次回再入院までの平均日数 は、平成 25 年度では、2 月が最短で 24.4 日であり、冬に退院 した患者が短期間で再入院している結果であった。石坂は、 「循 環器病の季節変動」において " 心不全増悪による入院が冬に多 くなる " ことを述べており、再入院が多い月(時期・気候等) を 見据えた指導を行うことで患者の QOL が向上し早期再入院 予防につながると考えた。そこで、ガイドラインを元に患者 の病期を把握し、心不全患者の早期再入院予防につなげるた めに、退院指導内容の見直しを行い指導にいかした。その結 果を、ここに報告する。 286 P-111 心房中隔欠損によるEisenmenger症候群を背景 とし、感染を契機に急性心不全を呈した一症例の 理学療法経験 川村 雄介 1)、松井 彩乃 1)、沼田 玄理 2)、齊藤 哲也 2)、田中 茂博 2) 公立昭和病院 リハビリテーション科、2)公立昭和病院 循環器内科 1) 成人先天性心疾患患者は高齢化に伴い心不全等の合併症を生 じる。今回,心房中隔欠損 (以下 ASD)による Eisenmenger 症候群 (以下 ES) を既往に持つ高齢患者が,感染を契機に急性 心不全 (以下 AHF) となった症例の理学療法を経験したので報 告する。 症例は 70 歳代男性。20 歳で ASD を指摘され外科治療を望ま ず,その後 ES を合併し NYHAII で経過。消化器感染を契機 に AHF となり入院。 理学療法は第 9 病日目より開始。Specific Activity Scale(以下 SAS)は 1Met 以下であった。運動時は SpO2 75%以上が許容 範囲とされ,深呼吸練習,息こらえの防止,頻繁に休憩をと り症状悪化防止に努めた。最終的に 50m 歩行と階段 5 段昇降 は自覚症状なく SpO2 80%前半で推移。それ以上の負荷は低 酸素血症悪化を招く為運動を制限した。SAS は 3Mets に改善 し第 30 病日目に退院した。 心不全と肺高血圧を考慮した理学療法は心肺機能維持だけで なく多臓器保護の観点からも重要である。本症例は医師と連 携して両方向性短絡による状態変化に注意し,過度な安静を 避けて運動許容範囲を明確にした介入が一助となり軽快した と考える。本症例を通して疾患特性を考慮した運動方法と生 活指導の重要性を学んだ。 P-112 当院CICUにおけるNPPV使用患者の調査 手塚 友加里 1)、高橋 亜由美 1)、谷本 周三 2)、青野 ひろみ 3)、田邉 健吾 2)、 安部 崇子 1) 1) 三井記念病院 CICU、2)三井記念病院 循環器内科、3)三井記念病院 呼吸 器内科 【目的】急性心不全 (AHF)の呼吸管理として非侵襲的陽圧換 気療法 (NPPV)が推奨されている。当院においても AHF に て入院した患者へ積極的に NPPV を使用しているが、中に は NPPV から気管内挿管へ移行する例もみられる。そのた め当院における AHF 患者への NPPV 使用が適切であるか調 査する。 【方法】 2012 年 4 月から 2013 年 12 月に AHF と診断さ れ NPPV を装着した症例に関し調査を実施。患者背景、治 療経過はカルテベースで市情報収集した。 【結果】全 287 例中 NPPV 装着症例は 89 例、入院時に気管内挿管された症例は 11 例であった。NPPV 装着症例のうち気管内挿管へ移行した症 例(移行群)は 4 例あったが心原性ショック症例は含まれてい なかった。【結論】AHF 症例に対する NPPV 使用は適切であ ると考える。 プログラム・抄録集 P-113 P-115 ペースメーカー、ICD植込み患者の運動耐容能 1) 2) 近藤 和夫 、吉田 泉 、櫻井 正之 2) 社会医療法人社団カレスサッポロ 北光記念病院 心臓リハビリテーション 室、2)社会医療法人社団カレスサッポロ 北光記念病院 循環器科 1) 茅本 洋平 1)、宮本 欣倫 2) 1) 脳神経センター 大田記念病院 リハビリテーション課、2)脳神経センター 大田記念病院 循環器内科 【背景】近年、75 歳以上の高齢者の増加に伴い脳卒中(CVA)者 であっても多臓器との重複疾患が問題となっている。CVA 者 の予後予測には身体機能を中心とした報告は散見するも内部 障害との関係を示した報告は少ない。【目的】当院に入院した 心原性脳塞栓症(CE)者のうち入院時の内部障害が予後に影響 するか明らかにすること。【対象】H24 年 4 月∼ H25 年 12 月に 当院に入院した 75 歳以上の初発 CE 者で、入院時の心・腎機 能が明確かつ発症前に歩行が可能であった 135 例【方法】 mRS の 0 ∼ 2 を良好群、3 ∼ 6 を不良群と定義した。パラメーター は 年 齢、 性 別、BNP、EF、E/E 、eGFR で あ る。 心・ 腎 機 能障害として心不全を BNP ≧ 100。収縮障害 (SHF)を EF < 50。拡張障害 (DHF)を E/E > 15 とし、慢性腎臓病 (CKD)を eGFR < 60 とした。これらを後方視的に調査した。【結果と 考察】転機不良群において女性、心不全罹患、SHF、DHF が 高率であった (それぞれ P=0.031、0.06、0.06、P=0.048)。CE 者における予後予測に入院時の性別や心機能障害も考慮する 必要性が示唆された P-114 心不全患者における低栄養状態は呼吸筋力を低下 させる 曽田 武史 1)、衣笠 良治 2)、片桐 茜 1)、山田 健作 2)、杉原 志伸 2)、 加藤 雅彦 2)、萩野 浩 1)、山本 一博 2) 1) 鳥取大学医学部附属病院 リハビリテーション部、2)鳥取大学医学部附属病 院 循環器内科 【目的】慢性心不全患者における栄養状態の悪化は四肢の骨 格筋力を低下させることが知られているが,呼吸筋力に及 ぼす影響については明らかにされていない。【方法】歩行が 可能な慢性心不全患者 40 名(年齢 75.0±12.7 歳 , 男性 55%)を 対象に、心不全患者の栄養評価の指標として提唱されてい る Geriatric nutritional risk index(GNRI)を算出し,92 未満 (低栄養群)と 92 以上 (正常群)に分け,握力,膝伸展筋力,呼 吸 筋 力(Maximum inspiratory pressure: MIP,Maximum expiratory pressure: MEP)6 分間歩行距離(6MWD)を 2 群で 比較した. 【結果】低栄養群は,正常群と比較して、高齢で、 握力,膝伸展筋力,MIP,MEP が有意に低値であった (P < 0.05) 。また、6MWD は低栄養群で低い傾向にあった(p = 0.054) 。 【結語】低栄養状態にある慢性心不全患者は四肢筋力 だけでなく、呼吸筋力の低下も認められ、骨格筋ならびに呼 吸筋のレジスタンストレーニングを併用した包括的な栄養・ リハビリ介入が必要と考えられる。 287 一般演題 ︵ポスター︶ 【目的】ペースメーカー(以下、PM)等植込みの身体障害者手 帳認定基準が、身体活動能力に応じた等級となった。そこで、 当院の PM 等植込み患者の運動耐容能(peak VO2)について 調査を行なった。 【対象と方法】CPX を実施した連続症例か らペースメーカー等植込み後に実施した症例の peak VO2 を カルテより調査した。心臓血管外科術後に植込みを行なった 症例を除外し、PM60 名(男性 39 名女性 21 名、平均 70.6 歳) 、 ICD46 名( 男 性 40 名 女 性 7 名、 平 均 66.3 歳)、CRT-P6 名 (男 性 2 名 女 性 4 名、 平 均 69.7 歳)、CRT-D25 名( 男 性 22 名 女 性 3 名、平均 68.3 歳)であった。【結果】peak VO2 平均値(ml/kg/ min)は、PM 群 12.4、ICD 群 12.3、CRT-P 群 11.4、CRT-D 群 12.4 であり、群間の差はなかった。2 メッツ未満の 1 級に該当 する症例は 8 名(PM 群 5 名、ICD 群 3 名)全体の 5.8%であり、 うち女性が 5 名であった。メッツは 3.5ml/kg/min を 1 メット とした。【考察】デバイスの種類に関係なく、運動耐容能は平 均 3.5 メッツであった。心機能の影響も大きいが、運動遂行困 難な原因は下肢疲労であることが多く、適切な生活、運動指 導によって今後改善することも考えられる。 高齢の心原性脳塞栓症者の予後についての調査 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 ポスター23(P23)HFpEF の様々な話題 P-116 Cessation of Taking βBlocker Ameliorates Oscillatory Ventilation During Exercise Yuko KATO1)、Tomoko HIMI2)、Osamu NAGAYAMA1)、 Etsuko HAYAMA1)、Kaori ISHII1)、Kouji SAKURADA1)、 Takeshi YAMASHITA1) The Cardiovascular Institute Hospital、2)Kawaguchi Kogyo General Hospital 1) 一般演題 ︵ポスター︶ 61 year-old woman was admitted to our hospital because of acute decompensated heart failure(HF)(clinical scenario classification 1, HFpEF). She was treated with decreasing blood pressure and administrating diuretics. After improved HF, she performed cardiopulmonary exercise testing (CPET). At the time of the first CPET, she was taking 8mg of candesartan and 1.25mg of bisoprolol. The first CPET showed obvious oscillatory ventilation through whole exercise testing. After the first CPET, she stopped taking bisoprolol because it has been thought to deteriorate her HF via increasing diastolic filling pressure due to shortening the duration of diastole. One week later, the second CPET showed an improving exercise capacity and an abatement of oscillatory ventilation (Figure). Heart rate apparently increased after cessation, which may ameliorate hemodynamics and improve every CPET variables. P-117 Arterial Stiffness is Significantly Associated with Left Ventricular Diastolic Dysfunction in Patients with Clinical Cardiovascular Disease P-118 Sex Difference in Mortality in Heart Failure with Preserved Ejection Fraction -A Report from the CHART-2 StudyKanako TSUJI、Yasuhiko SAKATA、Masanobu MIURA、Satoshi MIYATA、 Kotaro NOCHIOKA、Tsuyoshi TAKADA、Soichiro TADAKI、 Ryoichi USHIGOME、Takeshi YAMAUCHI、Hiroaki SHIMOKAWA Department of Cardiovascular Medicine and Department of EvidenceBased Cardiovascular Medicine, Tohoku University Graduate School of Medicine,Sendai,Japan Background: Sex difference remains to be fully examined in patients with heart failure with preserved ejection fraction(HFpEF). Methods : We examined sex difference in 3,124 consecutive HFpEF patients(EF>50%, mean 69.4years, 34.7% female)registered in the CHART-2 Study(n=10,219). Results : Female patients were characterized by higher age, higher NYHA class and higher BNP levels than males(Table). During the median 3.2-year follow-up, 392 patients(12.5%)died. Although the crude mortality was comparable between genders(hazard ratio(HR)1.18, P=0.11), the adjusted mortality risk was significantly low in females(HR 0.72, P=0.009). Female patients died due to cardiovascular causes more frequently than males(53.7% vs. 39.2%, P<0.01). Conclusions : Although female HFpEF patients had comparable all-cause mortality with males, they had severer HF and higher cardiovascular mortality than males. P-119 Pathogenesis and Prognostic Factors Involved in the HFpEF Takayuki NAMBA、Nobuyuki MASAKI、Hirotaka YADA、 Daihiko HAKUNO、Kouji MIYAZAKI、Takeshi ADACHI Yoshiaki KUBOTA、Kuniya ASAI、Daigo CHINEN、Aya YOSHINAGA、 Keisuke INUI、Shyunichi NAKAMURA、Kouji MURAI、 Masatomo YOSHIKAWA、Kouji KATOU、Wataru SHIMIZU The Department of Cardiology, National Defense Medical College, Tokorozawa,Japan DepartmentofCardiovascularMedicine,NipponMedicalSchoolHospital, Tokyo,Japan Backgroud: The cardio-ankle vascular index(CAVI)has been developed as a parameter of arterial stiffness. There are some previous reports about the association of arterial stiffness and left ventricular(LV)diastolic dysfunction in patients with subclinical atherosclerosis. However, there are few reports about this relationship in clinical cardiovascular disease. Methods: We measured parameters of arterial stiffness and LV systolic and diastolic function(LV ejection fraction, left atrial diameter, E/e' etc)by using CAVI and echocardiography in 80 patients of clinical cardiovascular disease. We also measured plasma BNP levels at the time of measurement of CAVI. Patients were divided into two groups, the higher CAVI group (CAVI>9)and the lower CAVI group(CAVI<9). Patients with atrial fibrillation, peripheral arterial disease, significant valvular disease were excluded. Results: In multivariate analysis, E/e' was significantly higher in patients of the higher CAVI group than the lower CAVI group(16.5± 7.7 and 13.4± 4.9, p=0.033). There were not significant relationship between CAVI and LV ejection fraction, left atrial diameter, or plasma BNP levels. Conclusion: A higher CAVI was independently associated with LV diastolic dysfunction in patients with clinical cardiovascular disease. The results suggested that aortic stiffness contributed to the development of LV diastolic heart failure. Background: Factors involved in the pathogenesis of heart failure with preserved ejection fraction(HFpEF)include hypertension (HTN), anemia, diabetes, obesity, and chronic obstructive pulmonary disease(COPD). On the other hand, few studies have examined the influence of these non-heart-associated concomitant diseases on the prognosis of patients with HFpEF.Subjects and Methods: We retrospectively analyzed 69 HTN patients who were admitted to our hospital with a diagnosis of HFpEF between January 2008 and March 2012 and could be followed-up for 2 years, excluding those with acute coronary syndrome, those undergoing dialysis and those with severe valvular disease. We evaluated the factors involved in all-cause mortality and rehospitalization due to HF.Results: The mean age of the subjects was 75.6±11.4 years, males accounted for 66.7%. The COPD was identified as a factor involved in all-cause mortality(HR: 2.71(1.01-7.23), P<0.05). On the other hand, chronic kidney disease and anemia was identified as a factor involved in rehospitalization due to HF(HR: 3.01(1.06-8.57), P<0.05, HR 2.65( 1.06-6.59)P<0.05, respectively).Conclusion: In HFpEF patients with HTN, factors involved in all-cause mortality may differ from those involved in rehospitalization due to HF. Not only HF treatment but also active management for individual concomitant diseases may be necessary to improve the prognosis. Treatment for COPD may also improve the prognosis. 288 プログラム・抄録集 ポスター24(P24)心筋疾患の臨床 P-120 Intensive Treatment of Atrial Fibrillation in Heart Failure with Preserved Ejection Fraction May be a Possible Option for Clinical Management Hiroaki HIRAIWA1)、Sumio YAMADA2)、Sayano KONDO1)、 Toru KONDO1)、Yasunori KANZAKI1)、Daisuke TANIMURA1)、 Toshiaki KATOH1)、Hiroaki SANO1)、Yoshifumi AWAJI1)、Rinya KATOH1) P-121 A Case Report of Successful Immunosuppressive Therapy for Chronic Myocarditis Haruka SATO、Tatsuo AOKI、Koichiro SUGIMURA、Kotaro NOCHIOKA、 Shunsuke TATEBE、Saori YAMAMOTO、Masanobu MIURA、 Nobuhiro YAOITA、Kimio SATOH、Hiroaki SHIMOKAWA Department of Cardiovascular Medicine, Tohoku University Graduate SchoolofMedicine,Sendai,Japan Background and Aims: Several hemodynamic factors contribute to decreased peak oxygen uptake(VO2peak)in heart failure with preserved ejection fraction(HFpEF). Atrial fibrillation(AF), frequent comorbidity with heart failure, can affect exercise hemodynamics by the loss of atrial kick. However, the influence of AF on VO2peak in HFpEF has not been fully investigated in Japanese patients.Therefore, we aimed to investigate the impact of AF on VO2peak and VE/VCO2 slope in Japanese patients with HFpEF(LVEF>50%). Methods: A total of ninety six patients with HFpEF(mean age 63±12 years; 79 male)who underwent cardiopulmonary testing were enrolled and divided into two groups; AF group(n=21)and non-AF group(n=75). Results: VO2peak was lower and VE/VCO2 slope was higher in AF group than non-AF group(VO2peak; 17.0±4.3 vs. 22.0±4.9 ml/min/kg, p<0.001, VE/ VCO2 slope; 33.0±6.5 vs. 28.3±5.8, p=0.006). In multiple linear regression analysis, age(β=-0.309, p=0.001), hemoglobin(β=0.342, p<0.001), and AF(β =-0.249, p=0.004)were selected as independent variables on VO2peak. When compared AF patients with age- and sex-matched non AF patients(n=21), VO2peak was significantly lower and VE/VCO2 slope was significantly higher in AF patients(VO2peak; 17.0±4.3 vs. 20.6±5.5 ml/min/kg, VE/VCO2 slope; 33.0±6.5 vs. 28.7±6.0). Conclusion: The findings of this study suggest that intensive care of AF may be a possible option for better prognosis in HFpEF patients. In February 2013, a 61-year-old woman admitted to a hospital for dyspnea. She was diagnosed as having heart failure(HF)due to dilated cardiomyopathy and medical therapies were started. However, she had repeated episodes of acute exacerbation of HF and admission to the hospital. In December 2013, she was transferred to our hospital for the treatment of her refractory HF. On admission, she had symptoms of NYHA III and elevated BNP level(1188 pg/ml). Cardiac MRI showed reduced left ventricular ejection fraction(LVEF, 22 %)and delayed enhancement in the apex. Right heart catheterization showed low cardiac index(CI, 2.03 L/min/ m2),and endomyocardial biopsy revealed lymphocytic infiltration, indicating chronic myocarditis. Chest X-ray and chest computed tomography showed multiple consolidations on both lungs, and transbronchial lung biopsy showed the presence of organizing pneumonia. Although tuberculin skin test was negative, FDG-PET, laboratory tests and endomyocardial and lung biopsies showed no other findings suggestive of cardiac sarcoidosis. Despite optimal treatments for HF, LVEF was not improved. In February 2014, we started immunosuppressive therapy with prednisolone(40 mg/day)and azathioprine(50 mg/day)with resultant improvement of LVEF(LVEF 41 %, CI 2.61 L/min/m2)in 2 weeks. Furthermore, endomyocardial biopsy after the immunosuppression therapy showed disappearance of lymphocytic infiltration in the myocardium. Thus, immunosuppressive therapy dramatically improved LV dysfunction in this case of chronic myocarditis. DepartmentofCardiology,NagoyaEkisaikaiHospital,Nagoya,Japan、 2) NagoyaUniversityGraduateSchoolofMedicine,Nagoya,Japan P-122 A Case of Cardiac Sarcoidosis with Acute Heart Failure Successfully Treated with Steroid Pulse Therapy Tomonari KIMURA、Kazufumi NAKAMURA、Koji TOKIOKA、 Toshihiro SARASHINA、Hironobu TODA、Yoko NODA、 Hiroshi ITO Cardiovasculardepartment,UniversityofOkayama,Okayama,Japan We report a case of cardiac sarcoidosis (CS) with acute heart failure, and successfully treated with steroid pulse therapy. A 64 year-old woman with left ventricular(LV)dysfunction was referred to our hospital because of acute heart failure and hypotension. Laboratory findings showed significant increase of serum high sensitive troponin T(hsTNT)level. Coronary artery angiography showed no coronary artery disease. Echocardiography showed decrease of mid to apex inferior wall motion. Cardiac magnetic resonance imaging showed late enhancement at several region of LV wall. 67Ga scintigraphy showed uptake by diffuse LV wall. Non-caseated epithilioid cell granulomas were observed in myocardial tissue, and diagnosed CS. The patient was treated with steroid pulse therapy(methyl prednisolone 500mg/day for 3days), the serum hsTNT decrease(from 1.41 to 0.300 ng/mL)and the worsening of LV wall motion stopped. Steroid pulse therapy was effective for CS with acute inflammation and acute heart failure. 289 一般演題 ︵ポスター︶ 1) 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 P-123 Cardiac Sarcoidosis with Ventricular Tachycardia and Echocardiography Mie SEYA、Taro SASAOKA、Kensuke HIRASAWA、 Shunji YOSHIKAWA、Yasuhiro MAEJIMA、Mihoko KAWABATA、 Masahiko GOYA、Takashi ASHIKAGA、Kenzo HIRAO、Mitsuaki ISOBE Department of Cardiovascular Medicine, Tokyo Medical and Dental University 一般演題 ︵ポスター︶ Background: Sarcoidosis is a multisystem disease, and cardiac sarcoidosis may be present in as many as 25 % of the patients with systemic sarcoidosis. Cardiac sarcoidosis affects patient's prognosis because of congestive heart failure and ventricular arrhythmias, however the details are remained to be elucidated. This study aimed to reveal the predictors of prognosis in patients with cardiac sarcoidosis.Methods and Results: We retrospectively analyzed consecutive 34 patients diagnosed cardiac sarcoidosis in our institution. Mean age of the patients were 62 ± 14 years old, and 24 patients(71%)were female. Solitary cardiac sarcoidosis was found in 10 patients (29%). 12 patients had decreased left ventricular ejection fraction(LVEF)(<50%)and 4 patients(12%)had the thinning of LV wall, 4 patients(12%)had no abnormal change of the echocardiography.VT(ventricular tachycardia)was tend to be occurred in patients with low EF(EF<50%)than with preserved EF(EF>50%). VT were observed in 13 patients (38%), and they had significantly lower LVEF compared to no-VT patients.(43 ± 14% vs. 58 ± 10% p=0.02)We found an optimal cut off value of 44% in ROC analysis, this value identified 7 of 13 patients with VT, resulting in sensitivity and specificity levels of 0.54 and 0.91. Conclusion: In this study, lower LVEF was associated with VT in cardiac sarcoidosis. P-124 Diagnosis and Treatment of Isolated Cardiac Sarcoidosis Daisuke TEZUKA、Taro SASAOKA、Mitsuaki ISOBE Department of Cardiovascular Medicine, Tokyo Medical and Dental University Background Long term survival data and the therapeutic significance of prednisolone for isolated cardiac sarcoidosis (iCS)has not been established, particularly in the cases with left ventricular( LV)dysfunction(EF < 50%). Moreover, it is difficult to diagnose iCS patients without histological evidence of granulomas. The aim of this study was to assess therapeutic effect and prognosis of iCS. Methods According to clinical criteria, sarcoidosis with CS (sCS)and iCS were diagnosed. iCS cases were examined using cardiac magnetic resonance imaging or 18F-fluoro2-deoxyglucose positron emission tomography/computed tomography. Results Baseline of brain natriuretic peptide( BNP)were not different between sCS(n=17)and iCS(n=7). After prednisolone treatment, BNP decreased significantly in both groups( sCS: before, 157.3±130.3 pg/ml; after, 108.8 ±93.7, p=0.01; iCS: before, 317.8±331.2; after, 138.6±161.6, p=0.043). The prognosis demonstrated by Kaplan-Meier curve( 40±51.1 months)was not different between sCS (n=30)and iCS(n=11). CS cases not treated by prednisolone showed poorer prognosis(p=0.0069). The patients with LV dysfunction which was not treated by prednisolone had the worst outcome among the all groups (p=0.0011). Conclusion iCS cases with LV dysfunction initially those suspected with the noninvasive imaging modalities, prednisolone treatment should be considered. 290 P-125 Heterogeneity of Sympathetic Nervous Density in the Left Ventricular Wall in Dilated Cardiomyopathy Shohei KIKUCHI、Shuichi KITADA、Nobuyuki OHTE Department of Cardio-Renal Medicine and Hypertension, Nagoya City UniversityGraduateSchoolofMedicalSciences,Nagoya,Japan Purpose: We assessed presynaptic sympathetic nervous function in patients with dilated cardiomyopathy( DCM)using positron emission tomography( PET)with Carbon-11 hydroxyephedrine (HED).Methods: In 15 patients with DCM in stable conditions and 15 healthy controls, left ventricular(LV)myocardial global blood flow(MBF)was measured using N-13 ammonia PET and then global HED retention index(HED-RI)was determined as myocardial tracer activity between 30-40 minutes divided by the integral of the activity input function. The polar maps of the tracers were divided into 17 segments, and each segmental tracer activity of MBF and HED-RI were normalized to the highest values in each patients. Coefficients of variation(CV)were calculated to assess heterogeneity of MBF and HED-RI in the LV wall. Results: MBF and HED-RI were significantly lower in patients with DCM than in healthy subjects(0.59±0.10 vs 0.78±0.10 mL/min/g, p=0.0003; 6.9±1.9 vs 8.8±2.0 %/min, p=0.02, respectively). CV of both MBF and HED-RI were significantly higher in patients with DCM than in healthy subjects(24.7±7.9 vs 17.5±4.1 %, p=0.004; 16.4±5.4 vs 10.3±2.2 %, p=0.0004, respectively). The CVs of HED-RI were significantly correlated with logBNP(r=0.65, p=0.0001). Conclusion: In addition to the global reduction of cardiac sympathetic activity, heterogeneous sympathetic presynaptic tracer uptake in the LV wall was demonstrated in patients with DCM. The degree of heterogeneity was correlated to severity of heart failure. プログラム・抄録集 ポスター25(P25)心不全におけるバイオマーカー P-126 P-128 Impact of Parathyroid Hormone on Future Occurrence of Heart Failure in Patients without History of Cardiovascular Disease Serum Brain-Derived Neurotrophic Factor Level Predicts Adverse Clinical Outcomes in Patients with Heart Failure Satoru SAKURAGI、Keiji YAMADA Masato KUDO、Shintaro KINUGAWA、Arata FUKUSHIMA、Takashi YOKOTA、 Shouji MATSUSHIMA、Takaaki FURIHATA、Masaya TSUDA、 Junichi MATSUMOTO、Shingo TAKADA、Hiroyuki TSUTSUI Departmentofcardiology,iwakuniClinicalCenter P-127 Department of Cardiovascular Medicine, Hokkaido University Graduate SchoolofMedicine,Sapporo,Japan Aims: Exercise intolerance as well as depressive symptoms are prevalent and associated with adverse outcomes in patients with heart failure( HF). Brain-derived neurotrophic factor( BDNF)is involved in cardiovascular diseases as well as skeletal muscle energy metabolism and depression. We recently reported that serum BDNF level was decreased in HF patients and was closely related to their exercise capacity. We thus investigated whether serum BDNF level was associated with their outcomes.Methods and Results: We measured serum BDNF level in 58 HF patients(59.2±13.7 years, NYHA I-III)at baseline and adverse events including all cause death and HF rehospitalization were registered during the mean follow-up of 18.2 months. The multivariate analysis demonstrated that serum BDNF level was an independent prognostic factor of adverse events (hazard ratio 2.32, 95% confidence interval 1.20-4.47, P=0.008). Cutoff value of serum BDNF determined by receiver operating characteristic curve analysis predicted adverse events with sensitivity, specificity, and positive and negative predictive values of 75%, 79%, 60%, and 85%, respectively. Kaplan-Meier analysis demonstrated that low level of BDNF was associated with higher rates of adverse events than high level of BDNF(P=0.001). Conclusion: Decreased serum BDNF levels were significantly associated with adverse outcomes in HF patients, suggesting that they can be a useful prognostic biomarker. P-129 Relationship Between Indoxyl Sulfate and Fibroblast Growth Factor 23 in Heart Failure Patients with Preserved Renal Function Serum Irisin Levels Provide Prognostic Information in Patients with Heart Failure with Reduced Ejection Fraction Miki IMAZU1)、Masanori ASAKURA1)、Hiroyuki TAKAHAMA1)、Hiroshi ASANUMA2)、 Akira FUNADA1)、Yasuo SUGANO1)、Takahiro OHARA1)、Takuya HASEGAWA1)、 Hideaki KANZAKI1)、Toshihisa ANZAI1)、Masafumi KITAKAZE1) Shinsuke HANATANI、Yasuhiro IZUMIYA、Yuichi KIMURA、 Yoshiro ONOUE、Satoshi ARAKI、Hisao OGAWA National Cerebral and Cardiovascular Center, Osaka, Japan、2)Kyoto PrefecturalUniversitySchoolofMedicine Introduction: Irisin is a newly identified myokine found in human serum. The gene expression of irisin precursor in skeletal muscle is associated with exercise tolerance in heart failure patients.Hypothesis: In patients with heart failure with reduced ejection fraction(HFrEF), irisin could be a useful biomarker to predict future cardiovascular events.Methods and results: We measured serum irisin levels in 84 patients with HFrEF. Serum irisin concentrations were measured by an ELISA. The endpoint was a composite of total mortality, cardiovascular hospitalization and coronary revascularization. These patients were divided into 2 groups according to irisin levels. Median irisin levels in each group were 45.77ng/ml and 64.72ng/ml, respectively. Low irisin group revealed significantly higher high sensitive troponin T levels than high irisin group(median 0.024, interquartile range [0.012-0.042] vs. 0.014, [0.008-0.023] ng/ml, p=0.006). Right heart catheterization demonstrated that pulmonary capillary wedge pressure is higher in the low than the high irisin group(15.9±7.0 vs. 12.3±5.8 mmHg, p=0.013). Kaplan Meier curve revealed that the event-free rate was decreased in the low irisin group(log-rank test p=0.042). In receiver operating characteristic analysis, irisin achieved an area under the curve of 0.67 for the identification of event free 1year survival(p=0.031).Conclusions: Irisin could be a useful biomarker for evaluating disease severity and providing prognostic information in patients with HFrEF. 1) Relationship between Indoxyl Sulfate and Fibroblast Growth Factor 23 in Heart Failure Patients with Preserved Renal Function Backgrounds: Both indoxyl sulfate(IS)known as one of a uremic toxin and fibroblast growth factor 23( FGF23)which is one of a phosphate-regulating hormone are known to be prognostic markers with chronic kidney disease. Recently it was reported that IS suppressed Klotho expression which need to FGF23 signaling in kidney, but it is less known the relationship between IS and FGF23. We aimed to determine the relationship in heart failure patients without advanced renal dysfunction. Methods: We investigated 726 subjects from a community population, and prospectively enrolled 79 patients who have history of heart failure with more than 60 ml/min/1.73 m2 of eGFR and without albuminuria(HF group). We matched community population with gender and eGFR of HF patients(Control group). The plasma IS levels and the serum FGF23 levels were measured at the same time. Results: IS levels significantly correlated with FGF23 levels in HF group(r=0.35, p=0.002), but not in Control group(r=0.07, p=0.521), and IS did not correlate with phosphorous and intact parathyroid hormone which relate to FGF23 in these groups. IS and FGF23 levels of HF group were significantly higher than of Control group, and BNP levels, too. Conclusion: IS related to FGF23 in HF patients without obvious renal dysfunction. IS might influence regulating the serum FGF23 levels CardiovascularMedicine,KumamotoUniversity,Kumamoto,Japan 291 一般演題 ︵ポスター︶ Parathyroid hormone(PTH)plays an important role in bone metabolism. High PTH level increases intracellular calcium in arterial wall, which causes hypertension and left ventricular hypertrophy. However, information on the association of PTH level with cardiovascular event in general population is still lacking.Methods and results174 subjects( 84male, 68years)without history of cardiovascular disease were enrolled from September 2012 to April 2013. At baseline, parathyroid function was assessed with intact PTH(iPTH). Subjects were classified into tertiles of intact PTH and clinical characteristics were compared. Association of intact PTH with future cardiovascular event was also evaluated. Subjects with highest tertile of iPTH was older, and had higher ratio of female and prevalence of hypertension(p < 0.05 for all). In blood test, markers of kidney function such as creatinine and cystatin C were increaed in subjects with highest tertile of iPTH. NT-proBNP increased with iPTH(p < 0.01). During the follow-up period of 115days, 7 subjects developed congestive heart failure. Serum intact iPTH was significantly associated with occurrence of heart failure(p < 0.05). This association was still significant after adjustment for age, gender, incidence of hypertension, diabetes mellitus and kidney function. ConclusionParathyroid hormone is associated with future heart failure. Our results suggest that treatment to reduced PTH level is helpful to prevent future cardiac event. 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 ポスター26(P26)トルバプタンを用いた心不全治療 P-130 Utility of Neutrophil to Lymphocyte Ratio for Predicting Sudden Cardiac Death in Patients with Ischemic and Non-Ischemic Chronic Heart Failure Takahisa YAMADA、Takashi MORITA、Shunsuke TAMAKI、 Masatake FUKUNAMI DivisionofCardiology,OsakaGeneralMedicalCenter 一般演題 ︵ポスター︶ The neutrophil to lymphocyte ratio(NLR)has been associated with poor outcome in patients with acute coronary syndrome. To investigate the prognostic significance of NLR for predicting sudden cardiac death(SCD)in patients with chronic heart failure (CHF), relating to the etiology(ischemic or non-ischemic), we studied 153 CHF outpatients(ischemic;51%)with LVEF<40% in our prospective cohort study. These patients underwent complete blood counts with automated differential counts, which included total white blood cell count, neutrophils, lymphocytes, red cell distribution width(RDW)and platelet cell distribution width (PDW), at baseline. During a follow up period of 7.6±4.3 yrs, 28 patients had SCD. At multivariate Cox analysis, only NLR was independently and significantly associated with SCD in both ischemic and non-ischemic groups, although percent neurophil, percent lymphocyte, RDW or PDW showed a significant association with SCD at univariate analysis. SCD was significantly observed in patients with high NLR(above the highest quartile)than low NLR, in ischemic(43% vs 14%, p=0.002)and nonischemic groups(38% vs 8%, p=0.003). The adjusted hazard ratios of high NLR for predicting SCD in ischemic and non-ischemic groups were 3.46(95%CI 1.04-11.49)and 3.72(95%CI 1.05-13.20), respectively. Thus, NLR has the long-term prognostic value for the prediction of SCD in CHF patients, irrespective of the etiology. P-131 P-132 Tolvaptan for Perioperative Heart Failure in Patients with Preoperative Pulmonary Congestion: Two Case Reports Aki KITAMURA、Keitaro NAKAGIRI The Department of Cardio-vascular Surgery, Ako City Hospital, Hyogo, Japan We report two cases of postoperative congestive heart failure (CHF)successfully treated with tolvaptan. Case 1. A 65-year-old man was admitted with chest pain and dyspnea.We diagnosed acute coronary syndrome(LMT)and CHF, so emergency CABG was performed. His P/F ratio was 110 because of pulmonary edema. According to Swan-Ganz data, he also had intravascular hypovolemia. Tolvaptan(15 mg)was administered and urine output was 4200 ml after 24 hours. His P/F ratio improved to 270, and extubation was possible on day 2.Case 2. A 26-yearold man was admitted with fatigue and fever.Severe mitral regurgitation due to infective endocarditis was diagnosed and he also had CHF with pulmonary hypertension and low cardiac output. We performed urgent mitral valve replacement. The early postoperative course was relatively smooth, and oral furosemide was initiated after extubation on day 3.However, CHF symptoms secondary to volume overload appeared on day 6. The chest X-ray film showed bilateral pleural effusions and an enlarged CTR. Echocardiography revealed impaired LV contraction and pulmonary hypertension. Oral tolvaptan (7.5 mg)was administered in addition to low-dose dobutamine. His body weight decreased by 8.2 kg after one week and CHF improved rapidly.Electrolyte imbalance did not occur and hemodynamics did not deteriorate in both patients.In conclusion, tolvaptan is effective for refractory CHF after cardiac surgery. P-133 Circulating Invariant Natural Killer T Cells are Decreased in Patients with Chronic Heart Failure The Use of Tolvaptan in a Case of Severe Heart Failure with Drug-Induced Cardiomyopathy Akimichi SAITO、Naoki ISHIMORI、Mikito NISHIKAWA、 Shintaro KINUGAWA、Hiroyuki TSUTSUI Taichi OKONOGI Department of Cardiovascular Medicine, Hokkaido University Graduate SchoolofMedicine,Sapporo,Japan Objective: Inflammation plays a crucial role in the development of chronic heart failure(HF). We have demonstrated that invariant natural killer T(iNKT)cells, a unique subset of T lymphocytes, have a protective role against left ventricular(LV)remodeling after myocardial infarction in mice. However, little is known about the changes in iNKT cells in patients with HF. Methods and Results: Nine patients with HF (NYHA II or III, LV ejection fraction 26.3±3.0%)and 8 healthy controls were studied. The number of circulating Vα24+ iNKT cells in peripheral blood by flow-cytometric analysis. The causes of HF were idiopathic dilated cardiomyopathy in 3, ischemic in 2, and others in 4 patients. Plasma BNP was significantly higher in HF(739.4±207.2 vs. 19.8± 6.5 pg/mL, P <0.01).The number of circulating iNKT cells and the ratio of the iNKT cell number to the total lymphocyte number were significantly lower in HF(747±85 vs. 1058±271 counts/ mL and 0.111±0.004 vs. 0.146±0.035%, respectively, both P <0.01). Plasma interleukin-6 and hs-CRP were significantly higher in HF(3.99±0.86 vs. 0.78±0.14 pg/mL and 0.28±0.10 vs. 0.06±0.02 mg/dL, respectively, both P <0.01). LV ejection fraction(r =0.72, P <0.05)and plasma logBNP(r =-0.70, P <0.05)were significantly correlated to iNKT cell ratio among HF patients. Conclusion: Circulating iNKT cells were decreased in patients with HF, indicating that they may be involved in this disease. 292 The Department of Cardiovascular Medicine, Heart Center, New YukuhashiHospital,Yukuhashi,Japan Tolvaptan is an oral vasopressin V2 receptor antagonist. Recently, many papers report the efficacy and safety of tolvaptan for patients with congestive heart failure. However, there is little information about clinical experience of the use of tolvaptan for a patient with drug-induced cardiomyopathy. A 52-year-old female with relapse breast cancer, invasive ductal carcinoma, treated by the CEF therapy(cyclophosphamide 800mg/day, epirubicin 100mg/day, 5-fluorouracil 800mg/ day). After she underwent her 15th cycle of the therapy, she was admitted to our hospital with dyspnea. The chest X-ray showed cardiomegaly with pulmonary congestion and pleural effusion. The transthoracic echocardiogram showed a left ventricular dysfunction with an ejection fraction of 35%. Her physical examination failed to indicate the cause of the heart failure. After analyzing some of her examination, we diagnosed epirubicin-induced cardiomyopathy. Treatments with furosemide, carperitide, low-dose dopamine and dobutamine are not useful in this case. Because the patient had a retention of fluid repeatedly, we administered a lowdose tolvaptan(7.5mg/day). As a result, her edema and body weight were reduced remarkably without worsening renal dysfunction, allowing her discharge from our hospital. It is possible that the use of tolvaptan enabled us to improve heart failure safety for patients with drug-induced cardiomyopathy. プログラム・抄録集 P-134 Tolvaptan was Effective in Patient with Heart Failure Due to Subclavian Arteriovenous Malformation Atsuko HIRAMINE、Takuro KUBOZONO、Shin KAWASOE、 Kunitsugu TAKASAKI、Akira KISANUKI、Masaaki MIYATA、 Mitsuru OHISHI Department of Cardiovascular Medicine and Hypertension, Graduate school of Medical and Dental Sciences, Kagoshima University, Kagoshima,Japan Efficacy and Safety of Tolvaptan Therapy for Acute Decompensated Heart Failure Toshijirou AOKI、Ryo YAMAGUCHI、Hideo OISHI、Yusuke MIKI、 Toshiki KAWAMIYA、Hitoshi ICHIMIYA、Yasuhiro UCHIDA、 Junji WATANABE、Masaaki KANASHIRO、Satoshi ICHIMIYA DepartmentofCardiology,YokkaichiMunicipalHospital,Mie,Japan Background: Diuretic use for acute decompensated heart failure(ADHF)is associated with electrolyte abnormalities and worsening renal function. The vasopressin antagonist tolvaptan may increase net volume loss without adversely affecting electrolytes and renal function. However, data on tolvaptan use for ADHF are limited even now. Method: Between March 2011 and February 2014, we enrolled 36 patients with ADHF who received tolvaptan in addition to standard medication therapy including diuretics. Patients were divided into two gropes; survival to hospital discharge (n = 30)and cardiac death in hospital(n = 6). We compared their clinical features, and assessed the efficacy and safety of tolvaptan therapy. Result: There was no side effect of tolvaptan such as acute elevation of serum sodium level, hypotension and deterioration of renal function. The baseline characteristics were almost similar between the two groups. But systolic blood pressure and estimated glomerular filtration rate(eGFR)on admission were lower in cardiac death group (125.8±32.5 mmHg vs 108.8±15.1 mmHg; p = 0.064 and 31.9 ±20.0 ml/min/1.73m2 vs 22.4±7.0 ml/min/1.73m2; p = 0.053, respectively).There was a positive correlation between eGFR and gain of the urine volume after starting tolvaptan(r = 0.58, p = 0.002). Conclusion: Tolvaptan therapy for ADHF is safe, but may not be effective for patients with renal dysfunction. P-135 Effects of Tolvaptan on Congestion and Neurohumoral Factors: A Case of Right Heart Failure Caused by Severe Tricuspid Regurgitation. Yodo TAMAKI、Yukiko HAYAMA、Naoaki ONISHI、Soichiro ENOMOTO、 Makoto MIYAKE、Toshihiro TAMURA、Hirokazu KONDO、 Kazuaki KAITANI、Chisato IZUMI、Yoshihisa NAKAGAWA DepartmentofCardiology,TenriHospital,Tenri,Japan We report a case of 74 year-old man with right heart failure caused by severe tricuspid regurgitation requiring frequent hospitalizations. The patient was admitted because of abdominal distension one month after discharge, gaining weight by 6kg. In the previous hospitalization just before discharge, cardiac index was 1.87 L/min/square meter and right atrial pressure was 19 mmHg in right heart catheterization. He declined surgery and was discharged on medical treatment. On admission, physical examination revealed massive ascites and cheat X-ray showed right dominant pleural effusion. Since he was already taking 80mg of furosemide, 16 mg of torasemide and 50mg of spironolactone, tolvaptan 7.5mg was added. Tolvaptan increased urinary output and decreased pleural effusion, ascites and body weight. He was discharged on 17th hospital day continuing to take tolvaptan. Plasma BNP decreased from 602.1 pg/ml to 260.4pg/ml. However, aldosterone increased from 116 pg/ml to 338 pg/ml and noradrenaline from 585 pg/ml to 1487 pg/ml. He is now visiting outpatient clinic, keeping his weight with no sign of congestion and has not been hospitalized for 1 year. In this case, tolvaptan was effective in preventing heart failure hospitalizations at the cost of neurohumoral activation. Further studies are needed to determine effects of long-term administration of tolvaptan. P-137 Clinical Efficacy and Safety of Tolvaptan in Very Elderly Patients with Acute Heart Failure Hiroki NIIKURA1)、Hitoshi ANNZAI1)、Hiroki TAKENAKA1)、Ryo FUKUI1)、 Norihiro KOUGAME1)、Junn KURIBARA1)、Naohiko NEMOTO1)、 Nobuyuki KOBAYASHI1)、Masato NAKAMURA2)、Kaoru SUGI2) Department of Cardiology, Ohta memorial hospital, Gunnma, Japan、 Division of Cardiovascular Medicine, Toho University Ohashi Medical Center 1) 2) Objective: We aim to assess the efficacy and safety of Tolvaptan(TLV)in very elderly patients(VEP)with acute heart failure(AHF). Patients and methods: We treated consecutive 77 AHF patients with TLV from March 2013 through March 2014. TLV was administered within 24 hours after admission. Patients with hypernatremia(over 145 mEq/L), acute coronary syndrome and dialysis were excluded in this study. Patients were divided into 2 groups(VEP; 85 yrs-old >/=, non VEP; <85 yrs-old)and were compared between 2 groups regarding in-hospital outcomes. Results: Two groups were identical in terms of patient backgrounds, concomitant treatment. Dose and duration of TLV. Conclusion: This study showed TLV was safely administered to VEP with AHF and provided the same clinical efficacy as those with non VEP. 293 一般演題 ︵ポスター︶ The patients with heart failure due to subclavian arteriovenous malformation are rare, and its treatment is difficult. Here, we report a 74-year-old male patient. In 1998, he was diagnosed with heart failure due to subclavian arteriovenous malformation and received medical treatment. Heart failure progressed, and he was treated with the coil embolism in 2009. However, the coil embolism was not effective to reduce the shunt flow and his symptom progressed slowly. He admitted because of general malaise and appetite loss, the edema was observed in his whole body, and the shunt flow was heard at his neck. The cardiomegaly and the pleural effusion were shown in a chest X-ray. The echocardiography demonstrated the dilatation of right atrium and ventricle and the severe tricuspid valve regurgitation with the cusp separation. He have been already treated with the high dose of diuretics including furosemide(80 mg/day),eplerenone(50 mg/ day)and trichlormethiazide(2 mg/day). It is not improved with low-salt diet and rest, and tolvapvtan(7.5 mg/day)was added. The urine volume increased after the administration of tolvaptan, and the body weight decreased by 7 kg in a week. His symptom of general fatigue improved and appetite also increased. In this case, tolvaptan was effective in the patient with heart failure due to subclavian arteriovenous malformation. P-136 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 ポスター27(P27)慢性心不全の睡眠時呼吸管理をどうするか? P-138 Change in Type of Sleep-Disordered Breathing from Predominant Central to Obstructive Sleep Apnea Following Coronary Artery Bypass Grafting Shoichiro YATSU1)、Takatoshi KASAI1,2)、Azusa MURATA1)、 Takao KATO1)、Shoko SUDA1,2)、Masaru HIKI1)、Eriko MATSUNAGA1)、 Tetsuro MIYAZAKI1)、Atsutoshi TAKAGI1)、Hiroyuki DAIDA1) Department of Cardiology, Juntendo University School of Medicine, Tokyo,Japan、2)Cardio-RespiratorySleepMedicine,Tokyo,Japan 1) 一般演題 ︵ポスター︶ Patients with heart failure( HF)frequently have central sleep apnea (CSA)due to hyperventilation associated with pulmonary congestion and increased chemosensitivity. On the other hand, CSA in HF patients may be improved by the initiation of specific therapy for failing heart. Several reports have shown that resolution of CSA or conversion of CSA to obstructive sleep apnea(OSA)was observed following surgical approaches for HF including mitral repair or cardiac transplant. We report the case of a 67-year-old overweight(body mass index, 26 kg/m2)man with reduced left ventricular ejection fraction(LVEF)due to myocardial infarction. He was initiated into implantable cardioverter defibrillator(ICD)therapy for frequent episodes of ventricular tachyarrhythmia and adaptive-servo ventilation for severe CSA. Since he had several episodes of appropriate ICD therapies, coronary angiogram was performed and three vessel disease with chronic total occlusion in left anterior descending was found. Then, he underwent coronary artery bypass grafting(CABG). After CABG, his LVEF increased slightly(from 38 to 42%)and B-type natriuretic level decreased(from 560 to 330 pg/ml). Although apnea-hypopnea index did not change(49.4 /h before CABG versus 55.1 /h after CABG),his CSA converted to predominant OSA accompanied by shortening of lung-tofinger circulation time(from 43 to 29 sec)2 weeks after CABG, which was completely suppressed with continuous positive airway pressure. P-139 A Case of Congestive Heart Failure Who Exhibited a Marked Improvement of Persistent Nocturnal Dyspnea Despite of Cardiac Resynchronization Therapy Takehiro TAMAKI、Yuuki IZUMI、Tsutomu YOSHIKAWA、 Jun UMEMURA、Tetsuya SUMIYOSHI、Hitonobu TOMOIKE D e p a r t m e n t o f C a r d i o l o g y S a k a k i b a r a H e a r t I n s t i t u t e J a p a n CardiovascularResearchPromotorSociety,Tokyo,Japan Adaptive servo-ventilation(ASV)has been originally applied to Cheyne-Stokes respiration which is seen in patients with advanced heart failure. This type of therapy directly alleviates sympatho-excitation and ameliorates hemodynamics, as well as improvement of oxygenation and respiration. It directly reduces both preload and afterload, resulting in reduction of total cardiac workload. Alternatively, it directly inhibits cardiac sympathetic outflow, especially in patients with heart failure. These effects altogether contribute to afterload reduction via reducing peripheral vascular resistance in acute phase. In addition, these effects elicit reverse remodeling of the left ventricle in patients with heart failure over the long-term observation. Here, we report a case who exhibited marked improvement of hemodynamics after introduction of ASV in advanced heart failure despite of cardiac resynchronization therapy. 294 P-140 Influence of Sleep Disordered Breathing on Heart Rate Turbulence in Heart Failure Patients Takeshi SHIMIZU、Akiomi YOSHIHISA、Minoru NODERA、 Yuichi NAKAMURA、Satoshi ABE、Satoshi SUZUKI、Kazuhiko NAKAZATO、 Hitoshi SUZUKI、Shu-Ichi SAITOH、Yasuchika TAKEISHI Department of Cardiology and Hematology, Fukushima Medical University,Fukushima,Japan Background: Sleep-disordered breathing(SDB)is associated with adverse outcomes in patients with heart failure(HF), while heart rate turbulence(HRT)assessed by Holter ECG has been used in order to predict sudden cardiac death. However, little is known about the relationship between SDB and HRT in HF patients. Methods and Results: 75 patients with HF and SDB were enrolled in this study. We simultaneously performed Holter ECG during 24-hr period and polysomnography in night time, and examined apnea hypopnea index(AHI)and HRT(turbulence onset and turbulence slope( TS))during 24-hr period. Patients were divided into two groups based on the presence of severe SDB: group A(AHI > 30, n = 17)and group B(AHI < 30, n = 58). TS was significantly lower in group A than in group B across the 24-hr period(nighttime: 3.6 ± 1.1 vs. 6.9 ± 1.3; daytime: 3.7 ± 0.8 vs. 7.0 ± 1.1; all-day: 3.5 ± 0.7 vs. 6.7 ± 0.9% ms/RR, P < 0.05, respectively). Furthermore, there was a significant negative correlation between all-day TS and AHI(R = -0.257, P = 0.027).Conclusions: Blunted TS was observed across a 24hour in patients with severe SDB. These results suggest that SDB may induce autonomic nervous modulation associated with poor prognosis across a 24-hour period in CHF patients. P-141 Time Course of Adaptive Servo-Ventilation Effects on Central Sleep Apnea in Patients with Chronic Heart Failure Takashi AKABANE、Shuji JOHO、Ryuichi USHIJIMA、 Yoshitaka ODA、Hiroshi INOUE The Second Department of Internal Medicine, University of Toyama, Toyama,Japan Background: Central sleep apnea(CSA)is prevalent in patients with heart failure(HF). Although adaptive servo-ventilation (ASV)suppresses CSA, it remains unknown whether long-term ASV leads to alleviation of CSA. Methods: Cardiorespiratory polygraphy and echocardiography were performed at baseline and 3.5 ± 0.8 months(mean ± SD)of follow-up in 28 patients with HF(NYHA II and III; left ventricular ejection fraction (LVEF)< 45%)and CSA(apnea-hypopnea index(AHI) 15/ h). Of these, 17 patients consented and 11 patients declined to undergo ASV treatment. Effect of ASV on AHI was confirmed with polygraphy and device integral counters. Result: Onenight ASV reduced AHI from 27 ± 15/h to 3 ± 3/h(p < 0.0001). AHI on ASV using device counters were similar with AHI measured by polygraphy. Long-term ASV alleviated AHI from 27 ± 15/h to 11 ± 7/h(p < 0.001). Difference between AHI at baseline and AHI on ASV was closely correlated with change in AHI between baseline and follow-up(R = 0.81, p<0.001). Change in LVEF was also correlated with the change in AHI. However, bivariate analysis revealed that the difference between AHI at baseline and AHI on ASV was an independent predictor of change in AHI. Conclusions: More suppression of CSA by ASV may relate to greater improvement of CSA irrespective of change of cardiac function. プログラム・抄録集 P-142 Acute Hemodynamic Effects of Adaptive Servo Ventilation in a Patient with Atrial Septal Defect Shinya FUJIKI1,2)、Hiroaki OBATA1)、Takeshi KASHIMURA1)、 Ritsuo WATANABE2)、Osamu OGAWA2)、Haruo HANAWA1)、 Tohru MINAMINO1) Department of cardiovascular biology and medicine, Niigata university graduate school of medical and dental sciences, Niigata, Japan、 Departmentofcardiology,NiigataPrefecturalCentralHospital,Niigata, Japan. 1) 2) 一般演題 ︵ポスター︶ Acute beneficial hemodynamic effects of adaptive servo ventilation (ASV)has been reported in patients with left-sided heart failure. However, little is known about its effects in patients with atrial septal defect(ASD).A 76 years-old female with ASD was admitted to our hospital for right-sided heart failure. After congestion was controlled, cardiac catheterization was performed. Her mean pulmonary artery pressure( mPAP)was 23mmHg with high pulmonary blood flow and normal pulmonary vascular resistance (Qp 10.95 l/min, Qs 6.01 l/min, Qp/Qs 1.83, PVR 138.8 dyne-seccm-5). ASV(EPAP 5, PS 3-10 cmH20, for 30min)decreased PVR by 44%(PVR: 89.4 dyne-sec-cm-5), although mPAP did not change with increased pulmonary blood flow(mPAP 23mmHg, Qp 14.32 l/min, Qs 6.55 l/min, Qp/Qs 2.19). These hemodynamic changes were observed with little difference in arterial oxygen saturation (SaO2: 93.3% in control and 94.7% under BiPAP, respectively), even though the changes were similar to those observed in this patient under oxygen inhalation(10 l/min, SaO2 99.8%, mPAP 23mmHg, Qp 16.5 l/min, Qs 6.94 l/min, Qp/Qs 2.39, PVR 77.3 dyne-sec-cm-5). This case shows that ASV can decrease PVR, even though its beneficial effect is offset by increased Qp. The mechanism underling the decrease of PVR is still to be elucidated. 295
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