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堀江 稔

所属部署名内科学講座(循環器内科)
職名教授
 
 
更新日: 18/02/20 15:25

研究者基本情報

氏名

    堀江 稔

所属(マスタ)

  • 内科学講座(循環器内科) 教授

学歴

  • - 1988年京都大学 医学研究科
  • - 1978年京都大学 医学部

学位

  • 医学博士(京都大学)

所属学協会

    臨床電気生理研究会 , 日本睡眠学会 , 日本核医学会 , 日本糖尿病学会 , 日本生理学会 , 日本内科学会 , 日本心不全学会 , 日本不整脈心電学会 , 日本循環器学会

経歴

  • 1988年大学院医学研究科、1988年〜京大病院循環器内科勤務、2002年から現職
  • - 1984年1978年京都大学卒業、〜1984年まで市立静岡市民病院内科、〜1988年京都大学

研究活動情報

論文

  • Association of Coronary Artery Calcification with Estimated Coronary Heart Disease Risk from Prediction Models in a Community-Based Sample of Japanese Men: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA).
    Tai Pham., Fujiyoshi A, Arima H, Tanaka-Mizuno S, Hisamatsu T, Kadowaki S, Kadota A, Zaid M, Sekikawa A, Yamamoto T, Horie M, Miura K, Ueshima H, Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) Research Group.
    Journal of atherosclerosis and thrombosis 2017年12月 [査読有り]
  • Refractory ventricular fibrillations after surgical repair of atrial septal defects in a patient with CACNA1C gene mutation - case report.
    Kojima A, Shikata F, Okamura T, Higaki T, Ohno S, Horie M, Uchita S, Kawanishi Y, Namiguchi K, Yasugi T, Izutani H
    Journal of cardiothoracic surgery 12(1) 118 2017年12月 [査読有り]
  • Macro-pro-B-type natriuretic peptide (proBNP) and hidden macro-N-terminal proBNP: Case report.
    Nakagawa Y, Nishikimi T, Sakai H, Ohno S, Kinoshita H, Inazumi H, Moriuchi K, Kuwahara K, Horie M, Kimura T
    Clinical biochemistry 2017年11月 [査読有り]
  • Different responses to exercise between Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia.
    Inoue YY, Aiba T, Kawata H, Sakaguchi T, Mitsuma W, Morita H, Noda T, Takaki H, Toyohara K, Kanaya Y, Itoi T, Mitsuhashi T, Sumitomo N, Cho Y, Yasuda S, Kamakura S, Kusano K, Miyamoto Y, Horie M, Shimizu W
    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2017年12月 [査読有り]
  • Impact of ABCB1, ABCG2, and CYP3A5 polymorphisms on plasma trough concentrations of apixaban in Japanese patients with atrial fibrillation.
    Ueshima S, Hira D, Fujii R, Kimura Y, Tomitsuka C, Yamane T, Tabuchi Y, Ozawa T, Itoh H, Horie M, Terada T, Katsura T
    Pharmacogenetics and genomics 27(9) 329-336 2017年09月 [査読有り]
  • Novel intracellular transport-refractory mutations in KCNH2 identified in patients with symptomatic long QT syndrome.
    Fukumoto D, Ding WG, Wada Y, Fujii Y, Ichikawa M, Takayama K, Fukuyama M, Kato K, Itoh H, Makiyama T, Omatsu-Kanbe M, Matsuura H, Horie M, Ohno S
    Journal of cardiology 2017年11月 [査読有り]
  • Single-session versus staged procedures for elective multivessel percutaneous coronary intervention.
    Toyota T, Morimoto T, Shiomi H, Yamaji K, Ando K, Ono K, Shizuta S, Saito N, Kato T, Kaji S, Furukawa Y, Nakagawa Y, Kadota K, Horie M, Kimura T, CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators.
    Heart (British Cardiac Society) 2017年11月 [査読有り]
  • Unique genetic background and outcome of non-Caucasian Japanese probands with arrhythmogenic right ventricular dysplasia/cardiomyopathy.
    Wada Y, Ohno S, Aiba T, Horie M
    Molecular genetics & genomic medicine 5(6) 639-651 2017年11月 [査読有り]
  • Arrhythmia risk and β-blocker therapy in pregnant women with long QT syndrome.
    Ishibashi K, Aiba T, Kamiya C, Miyazaki A, Sakaguchi H, Wada M, Nakajima I, Miyamoto K, Okamura H, Noda T, Yamauchi T, Itoh H, Ohno S, Motomura H, Ogawa Y, Goto H, Minami T, Yagihara N, Watanabe H, Hasegawa K, Terasawa A, Mikami H, Ogino K, Nakano Y, Imashiro S, Fukushima Y, Tsuzuki Y, Asakura K, Yoshimatsu J, Shiraishi I, Kamakura S, Miyamoto Y, Yasuda S, Akasaka T, Horie M, Shimizu W, Kusano K
    Heart (British Cardiac Society) 103(17) 1374-1379 2017年09月 [査読有り]
  • Progressive Atrial Conduction Defects Associated With Bone Malformation Caused by a Connexin-45 Mutation.
    Seki A, Ishikawa T, Daumy X, Mishima H, Barc J, Sasaki R, Nishii K, Saito K, Urano M, Ohno S, Otsuki S, Kimoto H, Baruteau AE, Thollet A, Fouchard S, Bonnaud S, Parent P, Shibata Y, Perrin JP, Le Marec H, Hagiwara N, Mercier S, Horie M, Probst V, Yoshiura KI, Redon R, Schott JJ, Makita N
    Journal of the American College of Cardiology 70(3) 358-370 2017年07月 [査読有り]
  • The relationship between J waves and contact of lung cancer with the heart.
    Hayashi H, Wu Q, Horie M
    Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc 22(5) 2017年09月 [査読有り]
  • Self-reported Sleep Duration and Subclinical Atherosclerosis in a General Population of Japanese Men.
    Suzuki S, Arima H, Miyazaki S, Fujiyoshi A, Kadota A, Takashima N, Hisamatsu T, Kadowaki S, Zaid M, Torii S, Horie M, Murata K, Miura K, Ueshima H, SESSA Research Group.
    Journal of atherosclerosis and thrombosis 2017年07月 [査読有り]
  • Long QT syndrome presents not only as QT prolongation but also as abnormal T-wave morphology.
    Horie M
    Heart rhythm 14(8) 1171-1172 2017年08月 [査読有り]
  • Heart failure in patients with arrhythmogenic right ventricular cardiomyopathy: What are the risk factors?
    Kimura Y, Noda T, Matsuyama TA, Otsuka Y, Kamakura T, Wada M, Ishibashi K, Inoue Y, Miyamoto K, Okamura H, Nagase S, Aiba T, Kamakura S, Noguchi T, Anzai T, Satomi K, Wada Y, Ohno S, Horie M, Shimizu W, Yasuda S, Shimokawa H, Kusano K
    International journal of cardiology 241 288-294 2017年08月 [査読有り]
  • Development of a Patient-Derived Induced Pluripotent Stem Cell Model for the Investigation of SCN5A-D1275N-Related Cardiac Sodium Channelopathy.
    Hayano M, Makiyama T, Kamakura T, Watanabe H, Sasaki K, Funakoshi S, Wuriyanghai Y, Nishiuchi S, Harita T, Yamamoto Y, Kohjitani H, Hirose S, Yokoi F, Chen J, Baba O, Horie T, Chonabayashi K, Ohno S, Toyoda F, Yoshida Y, Ono K, Horie M, Kimura T
    Circulation journal : official journal of the Japanese Circulation Society 81(12) 1783-1791 2017年06月 [査読有り]
  • Drug-induced fatal arrhythmias: Acquired long QT and Brugada syndromes.
    Turker I, Ai T, Itoh H, Horie M
    Pharmacology & therapeutics 176 48-59 2017年08月 [査読有り]
  • Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry.
    Yamagata K, Horie M, Aiba T, Ogawa S, Aizawa Y, Ohe T, Yamagishi M, Makita N, Sakurada H, Tanaka T, Shimizu A, Hagiwara N, Kishi R, Nakano Y, Takagi M, Makiyama T, Ohno S, Fukuda K, Watanabe H, Morita H, Hayashi K, Kusano K, Kamakura S, Yasuda S, Ogawa H, Miyamoto Y, Kapplinger JD, Ackerman MJ, Shimizu W
    Circulation 135(23) 2255-2270 2017年06月 [査読有り]
  • Incidence and Prognostic Impact of Heart Failure Hospitalization During Follow-Up After Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction.
    Taniguchi T, Shiomi H, Morimoto T, Watanabe H, Ono K, Shizuta S, Kato T, Saito N, Kaji S, Ando K, Kadota K, Furukawa Y, Nakagawa Y, Horie M, Kimura T
    The American journal of cardiology 119(11) 1729-1739 2017年06月 [査読有り]
  • Sick Sinus Syndrome with HCN4 Mutations Shows Early Onset and Frequent Association with Atrial Fibrillation and Left Ventricular Non-compaction.
    Ishikawa T, Ohno S, Murakami T, Yoshida K, Mishima H, Fukuoka T, Kimoto H, Sakamoto R, Ohkusa T, Aiba T, Nogami A, Sumitomo N, Shimizu W, Yoshiura KI, Horigome H, Horie M, Makita N
    Heart rhythm 14(5) 717-724 2017年01月 [査読有り]
  • Flecainide ameliorates arrhythmogenicity through NCX flux in Andersen-Tawil syndrome-iPS cell-derived cardiomyocytes.
    Kuroda Y, Yuasa S, Watanabe Y, Ito S, Egashira T, Seki T, Hattori T, Ohno S, Kodaira M, Suzuki T, Hashimoto H, Okata S, Tanaka A, Aizawa Y, Murata M, Aiba T, Makita N, Furukawa T, Shimizu W, Kodama I, Ogawa S, Kokubun N, Horigome H, Horie M, Kamiya K, Fukuda K
    Biochemistry and biophysics reports 9 245-256 2017年03月 [査読有り]
  • Allele-specific ablation rescues electrophysiological abnormalities in a human iPS cell model of long-QT syndrome with a CALM2 mutation.
    Yamamoto Y, Makiyama T, Harita T, Sasaki K, Wuriyanghai Y, Hayano M, Nishiuchi S, Kohjitani H, Hirose S, Chen J, Yokoi F, Ishikawa T, Ohno S, Chonabayashi K, Motomura H, Yoshida Y, Horie M, Makita N, Kimura T
    Human molecular genetics 26(9) 1670-1677 2017年05月 [査読有り]
  • Quantitative analysis of PKP2 and neighbouring genes in a patient with arrhythmogenic right ventricular cardiomyopathy caused by heterozygous PKP2 deletion.
    Sonoda K, Ohno S, Otuki S, Kato K, Yagihara N, Watanabe H, Makiyama T, Minamino T, Horie M
    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 19(4) 644-650 2017年04月 [査読有り]
  • J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge.
    Antzelevitch C, Yan GX, Ackerman MJ, Borggrefe M, Corrado D, Guo J, Gussak I, Hasdemir C, Horie M, Huikuri H, Ma C, Morita H, Nam GB, Sacher F, Shimizu W, Viskin S, Wilde AAM
    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 19(4) 665-694 2017年04月 [査読有り]
  • Ad hoc vs. Non-ad hoc Percutaneous Coronary Intervention Strategies in Patients With Stable Coronary Artery Disease.
    Toyota T, Morimoto T, Shiomi H, Ando K, Ono K, Shizuta S, Kato T, Saito N, Furukawa Y, Nakagawa Y, Horie M, Kimura T, CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators.
    Circulation journal : official journal of the Japanese Circulation Society 81(4) 458-467 2017年03月 [査読有り]
  • Cardiac conduction defects and Brugada syndrome: A family with overlap syndrome carrying a nonsense SCN5A mutation.
    Aoki H, Nakamura Y, Ohno S, Makiyama T, Horie M
    Journal of arrhythmia 33(1) 35-39 2017年02月 [査読有り]
  • Guidelines for Therapeutic Drug Monitoring of Cardiovascular Drugs Clinical Use of Blood Drug Concentration Monitoring (JCS 2015) - Digest Version.
    Aonuma K, Shiga T, Atarashi H, Doki K, Echizen H, Hagiwara N, Hasegawa J, Hayashi H, Hirao K, Ichida F, Ikeda T, Maeda Y, Matsumoto N, Sakaeda T, Shimizu W, Sugawara M, Totsuka K, Tsuchishita Y, Ueno K, Watanabe E, Hashiguchi M, Hirata S, Kasai H, Matsumoto Y, Nogami A, Sekiguchi Y, Shinohara T, Sugiyama A, Sumitomo N, Suzuki A, Takahashi N, Yukawa E, Homma M, Horie M, Inoue H, Ito H, Miura T, Ohe T, Shinozaki K, Tanaka K, Japanese Circulation Society and the Japanese Society of Therapeutic Drug Monitoring Joint Working Group.
    Circulation journal : official journal of the Japanese Circulation Society 81(4) 581-612 2017年03月 [査読有り]
  • Early repolarization and risk of arrhythmia events in long QT syndrome.
    Hasegawa K, Watanabe H, Hisamatsu T, Ohno S, Itoh H, Ashihara T, Hayashi H, Makiyama T, Minamino T, Horie M
    International journal of cardiology 223 540-542 2016年11月 [査読有り]
  • Contribution of a KCNH2 variant in genotyped long QT syndrome: Romano-Ward syndrome under double mutations and acquired long QT syndrome under heterozygote.
    Fujii Y, Matsumoto Y, Hayashi K, Ding WG, Tomita Y, Fukumoto D, Wada Y, Ichikawa M, Sonoda K, Ozawa J, Makiyama T, Ohno S, Yamagishi M, Matsuura H, Horie M, Itoh H
    Journal of cardiology 70(1) 74-79 2016年11月 [査読有り]
  • Extensive Ca2+ leak through K4750Q cardiac ryanodine receptors caused by cytosolic and luminal Ca2+ hypersensitivity.
    Uehara A, Murayama T, Yasukochi M, Fill M, Horie M, Okamoto T, Matsuura Y, Uehara K, Fujimoto T, Sakurai T, Kurebayashi N
    The Journal of general physiology 149(2) 199-218 2017年01月 [査読有り]
  • Elimination of Ventricular Arrhythmia in Catecholaminergic Polymorphic Ventricular Tachycardia by Targeting "Catecholamine-sensitive area": A Dominant-Subordinate Relationship between Origin Sites of Bidirectional Ventricular Premature Contractions.
    Shirai Y, Goya M, Ohno S, Horie M, Doi S, Isobe M, Hirao K
    Pacing and clinical electrophysiology : PACE 40(5) 600-604 2016年12月 [査読有り]
  • LMNA cardiomyopathy detected in Japanese arrhythmogenic right ventricular cardiomyopathy cohort.
    Kato K, Takahashi N, Fujii Y, Umehara A, Nishiuchi S, Makiyama T, Ohno S, Horie M
    Journal of cardiology 68(4) 346-351 2016年10月 [査読有り]
  • J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge.
    Antzelevitch C, Yan GX, Ackerman MJ, Borggrefe M, Corrado D, Guo J, Gussak I, Hasdemir C, Horie M, Huikuri H, Ma C, Morita H, Nam GB, Sacher F, Shimizu W, Viskin S, Wilde AA
    Heart rhythm 13(10) e295-324 2016年10月 [査読有り]
  • J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge.
    Antzelevitch C, Yan GX, Ackerman MJ, Borggrefe M, Corrado D, Guo J, Gussak I, Hasdemir C, Horie M, Huikuri H, Ma C, Morita H, Nam GB, Sacher F, Shimizu W, Viskin S, Wilde AA
    Journal of arrhythmia 32(5) 315-339 2016年10月 [査読有り]
  • Molecular pathogenesis of long QT syndrome type 1.
    Wu J, Ding WG, Horie M
    Journal of arrhythmia 32(5) 381-388 2016年10月 [査読有り]
  • A type 2 ryanodine receptor variant associated with reduced Ca2+ release and short-coupled torsades de pointes ventricular arrhythmia.
    Fujii Y, Itoh H, Ohno S, Murayama T, Kurebayashi N, Aoki H, Blancard M, Nakagawa Y, Yamamoto S, Matsui Y, Ichikawa M, Sonoda K, Ozawa T, Ohkubo K, Watanabe I, Guicheney P, Horie M
    Heart rhythm : the official journal of the Heart Rhythm Society 14(1) 98-107 2016年10月 [査読有り]
  • Genetics of Brugada syndrome.
    Juang JJ, Horie M
    Journal of arrhythmia 32(5) 418-425 2016年10月 [査読有り]
  • Molecular genetics have opened a new era for arrhythmia research, but also Pandora׳s box?
    Horie M
    Journal of arrhythmia 32(5) 313-314 2016年10月 [査読有り]
  • Patient-Specific Human Induced Pluripotent Stem Cell Model Assessed with Electrical Pacing Validates S107 as a Potential Therapeutic Agent for Catecholaminergic Polymorphic Ventricular Tachycardia.
    Sasaki K, Makiyama T, Yoshida Y, Wuriyanghai Y, Kamakura T, Nishiuchi S, Hayano M, Harita T, Yamamoto Y, Kohjitani H, Hirose S, Chen J, Kawamura M, Ohno S, Itoh H, Takeuchi A, Matsuoka S, Miura M, Sumitomo N, Horie M, Yamanaka S, Kimura T
    PloS one 11(10) e0164795 2016年10月 [査読有り]
  • Phenotypic Variability of ANK2 Mutations in Patients With Inherited Primary Arrhythmia Syndromes.
    Ichikawa M, Aiba T, Ohno S, Shigemizu D, Ozawa J, Sonoda K, Fukuyama M, Itoh H, Miyamoto Y, Tsunoda T, Makiyama T, Tanaka T, Shimizu W, Horie M
    Circulation journal : official journal of the Japanese Circulation Society 80(12) 2435-2442 2016年10月 [査読有り]
  • Variants in the SCN5A Promoter Associated With Various Arrhythmia Phenotypes.
    Yagihara N, Watanabe H, Barnett P, Duboscq-Bidot L, Thomas AC, Yang P, Ohno S, Hasegawa K, Kuwano R, Chatel S, Redon R, Schott JJ, Probst V, Koopmann TT, Bezzina CR, Wilde AA, Nakano Y, Aiba T, Miyamoto Y, Kamakura S, Darbar D, Donahue BS, Shigemizu D, Tanaka T, Tsunoda T, Suda M, Sato A, Minamino T, Endo N, Shimizu W, Horie M, Roden DM, Makita N
    Journal of the American Heart Association 5(9) 2016年09月 [査読有り]
  • Embryonic type Na+ channel β-subunit, SCN3B masks the disease phenotype of Brugada syndrome.
    Okata S, Yuasa S, Suzuki T, Ito S, Makita N, Yoshida T, Li M, Kurokawa J, Seki T, Egashira T, Aizawa Y, Kodaira M, Motoda C, Yozu G, Shimojima M, Hayashiji N, Hashimoto H, Kuroda Y, Tanaka A, Murata M, Aiba T, Shimizu W, Horie M, Kamiya K, Furukawa T, Fukuda K
    Scientific reports 6 34198 2016年09月 [査読有り]
  • Asymmetry of parental origin in long QT syndrome: preferential maternal transmission of KCNQ1 variants linked to channel dysfunction.
    Itoh H, Berthet M, Fressart V, Denjoy I, Maugenre S, Klug D, Mizusawa Y, Makiyama T, Hofman N, Stallmeyer B, Zumhagen S, Shimizu W, Wilde AA, Schulze-Bahr E, Horie M, Tezenas du Montcel S, Guicheney P
    European journal of human genetics : EJHG 24(8) 1160-1166 2016年08月 [査読有り]
  • Relationship of Insulin Resistance to Prevalence and Progression of Coronary Artery Calcification Beyond Metabolic Syndrome Components: Shiga Epidemiological Study of Subclinical Atherosclerosis.
    Yamazoe M, Hisamatsu T, Miura K, Kadowaki S, Zaid M, Kadota A, Torii S, Miyazawa I, Fujiyoshi A, Arima H, Sekikawa A, Maegawa H, Horie M, Ueshima H, SESSA Research Group.
    Arteriosclerosis, thrombosis, and vascular biology 36(8) 1703-1708 2016年08月 [査読有り]
  • Smoking, Smoking Cessation, and Measures of Subclinical Atherosclerosis in Multiple Vascular Beds in Japanese Men.
    Hisamatsu T, Miura K, Arima H, Kadota A, Kadowaki S, Torii S, Suzuki S, Miyagawa N, Sato A, Yamazoe M, Fujiyoshi A, Ohkubo T, Yamamoto T, Murata K, Abbott RD, Sekikawa A, Horie M, Ueshima H, Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) Research GroupNakanoYasutakaOgawaEmikoMaegawaHiroshiMiyazawaItsukoMitsunamiKenichiNozakiKazuhikoShiinoAkihikoArakiIsaoTsuruTeruhikoToyamaIkuoOgitaHisakazuKuritaSouichiMaedaToshinagaMiyamatsuNaomiKitaToruKimuraTakeshiNishioYoshihikoNakamuraYasuyukiOkamuraTomonoriBarinas‐MitchellEmma J.M.EdmundowiczDanielOhkuboTakayoshiHozawaAtsushiOkudaNagakoHigashiyamaAyaNagasawaShinyaKitaYoshikuniMurakamiYoshitakaTakashimaNaoyukiKadowakiTakash.
    Journal of the American Heart Association 5(9) 2016年08月 [査読有り]
  • Significance of integrated in silico transmural ventricular wedge preparation models of human non-failing and failing hearts for safety evaluation of drug candidates.
    Kubo T, Ashihara T, Tsubouchi T, Horie M
    Journal of pharmacological and toxicological methods 83 30-41 2016年08月 [査読有り]
  • Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) Associated With Ryanodine Receptor (RyR2) Gene Mutations - Long-Term Prognosis After Initiation of Medical Treatment.
    Kawata H, Ohno S, Aiba T, Sakaguchi H, Miyazaki A, Sumitomo N, Kamakura T, Nakajima I, Inoue YY, Miyamoto K, Okamura H, Noda T, Kusano K, Kamakura S, Miyamoto Y, Shiraishi I, Horie M, Shimizu W
    Circulation journal : official journal of the Japanese Circulation Society 80(9) 1907-1915 2016年08月 [査読有り]
  • Associations of serum LDL particle concentration with carotid intima-media thickness and coronary artery calcification.
    Zaid M, Miura K, Fujiyoshi A, Abbott RD, Hisamatsu T, Kadota A, Arima H, Kadowaki S, Torii S, Miyagawa N, Suzuki S, Takashima N, Ohkubo T, Sekikawa A, Maegawa H, Horie M, Nakamura Y, Okamura T, Ueshima H, SESSA Research Group.
    Journal of clinical lipidology 10(5) 1195-1202.e1 2016年09月 [査読有り]
  • Comparison of circadian, weekly, and seasonal variations of electrical storms and single events of ventricular fibrillation in patients with Brugada syndrome.
    Aizawa Y, Takatsuki S, Kaneko Y, Noda T, Katsumata Y, Nishiyama T, Kimura T, Nishiyama N, Fukumoto K, Niwano S, Kurita T, Mitsuhashi T, Kamakura S, Shimizu A, Horie M, Aizawa Y, Fukuda K
    International journal of cardiology. Heart & vasculature 11 104-110 2016年06月 [査読有り]
  • The genetics underlying acquired long QT syndrome: impact for genetic screening.
    Itoh H, Crotti L, Aiba T, Spazzolini C, Denjoy I, Fressart V, Hayashi K, Nakajima T, Ohno S, Makiyama T, Wu J, Hasegawa K, Mastantuono E, Dagradi F, Pedrazzini M, Yamagishi M, Berthet M, Murakami Y, Shimizu W, Guicheney P, Schwartz PJ, Horie M
    European heart journal 37(18) 1456-1464 2016年05月 [査読有り]
  • Inter-Facility Transfer vs. Direct Admission of Patients With ST-Segment Elevation Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.
    Nakatsuma K, Shiomi H, Morimoto T, Furukawa Y, Nakagawa Y, Ando K, Kadota K, Yamamoto T, Suwa S, Horie M, Kimura T, CREDO-Kyoto AMI investigators.
    Circulation journal : official journal of the Japanese Circulation Society 80(8) 1764-1772 2016年07月 [査読有り]
  • Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy.
    Freyermuth F, Rau F, Kokunai Y, Linke T, Sellier C, Nakamori M, Kino Y, Arandel L, Jollet A, Thibault C, Philipps M, Vicaire S, Jost B, Udd B, Day JW, Duboc D, Wahbi K, Matsumura T, Fujimura H, Mochizuki H, Deryckere F, Kimura T, Nukina N, Ishiura S, Lacroix V, Campan-Fournier A, Navratil V, Chautard E, Auboeuf D, Horie M, Imoto K, Lee KY, Swanson MS, Lopez de Munain A, Inada S, Itoh H, Nakazawa K, Ashihara T, Wang E, Zimmer T, Furling D, Takahashi MP, Charlet-Berguerand N
    Nature communications 7 11067 2016年04月 [査読有り]
  • Practical applicability of landiolol, an ultra-short-acting β1-selective blocker, for rapid atrial and ventricular tachyarrhythmias with left ventricular dysfunction.
    Wada Y, Aiba T, Tsujita Y, Itoh H, Wada M, Nakajima I, Ishibashi K, Okamura H, Miyamoto K, Noda T, Sugano Y, Kanzaki H, Anzai T, Kusano K, Yasuda S, Horie M, Ogawa H
    Journal of arrhythmia 32(2) 82-88 2016年04月 [査読有り]
  • Lipoprotein-associated phospholipase A2 is related to risk of subclinical atherosclerosis but is not supported by Mendelian randomization analysis in a general Japanese population.
    Ueshima H, Kadowaki T, Hisamatsu T, Fujiyoshi A, Miura K, Ohkubo T, Sekikawa A, Kadota A, Kadowaki S, Nakamura Y, Miyagawa N, Okamura T, Kita Y, Takashima N, Kashiwagi A, Maegawa H, Horie M, Yamamoto T, Kimura T, Kita T, ACCESS and SESSA Research Groups.
    Atherosclerosis 246 141-147 2016年03月 [査読有り]
  • Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for Atrial Fibrillation (EAST-AF) trial.
    Kaitani K, Inoue K, Kobori A, Nakazawa Y, Ozawa T, Kurotobi T, Morishima I, Miura F, Watanabe T, Masuda M, Naito M, Fujimoto H, Nishida T, Furukawa Y, Shirayama T, Tanaka M, Okajima K, Yao T, Egami Y, Satomi K, Noda T, Miyamoto K, Haruna T, Kawaji T, Yoshizawa T, Toyota T, Yahata M, Nakai K, Sugiyama H, Higashi Y, Ito M, Horie M, Kusano KF, Shimizu W, Kamakura S, Morimoto T, Kimura T, Shizuta S, EAST-AF Trial Investigators.
    European heart journal 37(7) 610-618 2016年02月 [査読有り]
  • Evaluation and management of bradycardia in neonates and children.
    Baruteau AE, Perry JC, Sanatani S, Horie M, Dubin AM
    European journal of pediatrics 175(2) 151-161 2016年02月 [査読有り]
  • High Frequency of Early Repolarization and Brugada-Type Electrocardiograms in Hypercalcemia.
    Sonoda K, Watanabe H, Hisamatsu T, Ashihara T, Ohno S, Hayashi H, Horie M, Minamino T
    Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc 21(1) 30-40 2016年01月 [査読有り]
  • Cardiac sodium channel mutation associated with epinephrine-induced QT prolongation and sinus node dysfunction.
    Chen J, Makiyama T, Wuriyanghai Y, Ohno S, Sasaki K, Hayano M, Harita T, Nishiuchi S, Yuta Yamamoto, Ueyama T, Shimizu A, Horie M, Kimura T
    Heart rhythm 13(1) 289-298 2016年01月 [査読有り]
  • Long-term outcomes associated with prolonged PR interval in the general Japanese population.
    Hisamatsu T, Miura K, Fujiyoshi A, Okamura T, Ohkubo T, Nagasawa SY, Horie M, Okayama A, Ueshima H, NIPPON DATA80 Research Group.
    Int J Cardiol 184(C) 291-293 2015年04月 [査読有り]
  • Pediatric Cohort With Long QT Syndrome - KCNH2 Mutation Carriers Present Late Onset But Severe Symptoms.
    Ozawa J, Ohno S, Hisamatsu T, Itoh H, Makiyama T, Suzuki H, Saitoh A, Horie M
    Circulation journal : official journal of the Japanese Circulation Society 80(3) 696-702 2016年 [査読有り]
  • Irbesartan-mediated AT1 receptor blockade attenuates hyposmotic-induced enhancement of I Ks current and prevents shortening of action potential duration in atrial myocytes.
    Wu J, Ding WG, Zhao J, Zang WJ, Matsuura H, Horie M
    Journal of the renin-angiotensin-aldosterone system : JRAAS 15(4) 341-347 2014年12月 [査読有り]
  • High long-chain n-3 fatty acid intake attenuates the effect of high resting heart rate on cardiovascular mortality risk: A 24-year follow-up of Japanese general population.
    Hisamatsu T, Miura K, Ohkubo T, Yamamoto T, Fujiyoshi A, Miyagawa N, Kadota A, Takashima N, Okuda N, Yoshita K, Kita Y, Murakami Y, Nakamura Y, Okamura T, Horie M, Okayama A, Ueshima H, NIPPON DATA80 Research Group.
    J Cardiol 64(3) 218-24 2014年09月 [査読有り]
  • Multigenerational Inheritance of Long QT Syndrome Type 2 in a Japanese Family.
    Ichikawa M, Ohno S, Fujii Y, Ozawa J, Sonoda K, Fukuyama M, Kato K, Kimura H, Itoh H, Hayashi H, Horie M
    Internal medicine (Tokyo, Japan) 55(3) 259-262 2016年 [査読有り]
  • Long QT syndrome type 8: novel CACNA1C mutations causing QT prolongation and variant phenotypes.
    Fukuyama M, Wang Q, Kato K, Ohno S, Ding WG, Toyoda F, Itoh H, Kimura H, Makiyama T, Ito M, Matsuura H, Horie M
    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 16(12) 1828-1837 2014年12月 [査読有り]
  • Author reply: To PMID 24394973.
    Ohno S, Horie M
    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 16(12) 1864-1865 2014年12月 [査読有り]
  • Lipoprotein particle profiles compared with standard lipids in association with coronary artery calcification in the general Japanese population.
    Hisamatsu T, Fujiyoshi A, Miura K, Ohkubo T, Kadota A, Kadowaki S, Kadowaki T, Yamamoto T, Miyagawa N, Zaid M, Torii S, Takashima N, Murakami Y, Okamura T, Horie M, Ueshima H, SESSA Research Group.
    Atherosclerosis 236(2) 237-243 2014年10月 [査読有り]
  • Association between Progressive Intraventricular Conduction Disturbance and Cardiovascular Events.
    Hayashi H, Wu Q, Horie M
    PloS one 11(7) e0157412 2016年 [査読有り]
  • A Novel SCN5A Mutation Associated with Drug Induced Brugada Type ECG.
    Turker I, Makiyama T, Vatta M, Itoh H, Ueyama T, Shimizu A, Ai T, Horie M
    PloS one 11(8) e0161872 2016年 [査読有り]
  • Adenosine triphosphate-guided pulmonary vein isolation for atrial fibrillation: the UNmasking Dormant Electrical Reconduction by Adenosine TriPhosphate (UNDER-ATP) trial.
    Kobori A, Shizuta S, Inoue K, Kaitani K, Morimoto T, Nakazawa Y, Ozawa T, Kurotobi T, Morishima I, Miura F, Watanabe T, Masuda M, Naito M, Fujimoto H, Nishida T, Furukawa Y, Shirayama T, Tanaka M, Okajima K, Yao T, Egami Y, Satomi K, Noda T, Miyamoto K, Haruna T, Kawaji T, Yoshizawa T, Toyota T, Yahata M, Nakai K, Sugiyama H, Higashi Y, Ito M, Horie M, Kusano KF, Shimizu W, Kamakura S, Kimura T, UNDER-ATP Trial Investigators.
    European heart journal 36(46) 3276-3287 2015年12月 [査読有り]
  • Biphasic P wave in inferior leads and the development of atrial fibrillation.
    Hayashi H, Horie M
    Journal of arrhythmia 31(6) 376-380 2015年12月 [査読有り]
  • The association of J wave and ventricular tachycardia before device implantation with device interventions for ventricular tachyarrhythmia.
    Hayashi H, Horie M
    Journal of electrocardiology 48(4) 721-728 2015年07月 [査読有り]
  • Efficacy and safety of flecainide for ventricular arrhythmias in patients with Andersen-Tawil syndrome with KCNJ2 mutations.
    Miyamoto K, Aiba T, Kimura H, Hayashi H, Ohno S, Yasuoka C, Tanioka Y, Tsuchiya T, Yoshida Y, Hayashi H, Tsuboi I, Nakajima I, Ishibashi K, Okamura H, Noda T, Ishihara M, Anzai T, Yasuda S, Miyamoto Y, Kamakura S, Kusano K, Ogawa H, Horie M, Shimizu W
    Heart rhythm 12(3) 596-603 2015年03月 [査読有り]
  • Gender Differences in the Inheritance Mode of RYR2 Mutations in Catecholaminergic Polymorphic Ventricular Tachycardia Patients.
    Ohno S, Hasegawa K, Horie M
    PloS one 10(6) e0131517 2015年 [査読有り]
  • A Common Mutation of Long QT Syndrome Type 1 in Japan.
    Itoh H, Dochi K, Shimizu W, Denjoy I, Ohno S, Aiba T, Kimura H, Kato K, Fukuyama M, Hasagawa K, Schulze-Bahr E, Guicheney P, Horie M
    Circulation journal : official journal of the Japanese Circulation Society 79(9) 2026-2030 2015年 [査読有り]
  • Association between Pulse Wave Velocity and Coronary Artery Calcification in Japanese men.
    Torii S, Arima H, Ohkubo T, Fujiyoshi A, Kadota A, Takashima N, Kadowaki S, Hisamatsu T, Saito Y, Miyagawa N, Zaid M, Murakami Y, Abbott RD, Horie M, Miura K, Ueshima H, SESSA Research Group.
    Journal of atherosclerosis and thrombosis 22(12) 1266-1277 2015年 [査読有り]
  • Löffler Endocarditis and Lacking Heart.
    Sawayama Y, Itoh H, Sakai H, Horie M
    Internal medicine (Tokyo, Japan) 54(23) 3093 2015年 [査読有り]
  • Circadian pattern of fibrillatory events in non-Brugada-type idiopathic ventricular fibrillation with a focus on J waves.
    Aizawa Y, Sato M, Ohno S, Horie M, Takatsuki S, Fukuda K, Chinushi M, Usui T, Aonuma K, Hosaka Y, Haissaguerre M, Aizawa Y
    Heart rhythm 11(12) 2261-2266 2014年12月 [査読有り]
  • Electrical storm in patients with brugada syndrome is associated with early repolarization.
    Kaneko Y, Horie M, Niwano S, Kusano KF, Takatsuki S, Kurita T, Mitsuhashi T, Nakajima T, Irie T, Hasegawa K, Noda T, Kamakura S, Aizawa Y, Yasuoka R, Torigoe K, Suzuki H, Ohe T, Shimizu A, Fukuda K, Kurabayashi M, Aizawa Y
    Circulation. Arrhythmia and electrophysiology 7(6) 1122-1128 2014年12月 [査読有り]
  • Comparison of long-term mortality after acute myocardial infarction treated by percutaneous coronary intervention in patients living alone versus not living alone at the time of hospitalization.
    Nakatsuma K, Shiomi H, Watanabe H, Morimoto T, Taniguchi T, Toyota T, Furukawa Y, Nakagawa Y, Horie M, Kimura T, CREDO-Kyoto AMI Investigators.
    The American journal of cardiology 114(4) 522-527 2014年08月 [査読有り]
  • Anticoagulant and antiplatelet therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention.
    Goto K, Nakai K, Shizuta S, Morimoto T, Shiomi H, Natsuaki M, Yahata M, Ota C, Ono K, Makiyama T, Nakagawa Y, Furukawa Y, Kadota K, Takatsu Y, Tamura T, Takizawa A, Inada T, Doi O, Nohara R, Matsuda M, Takeda T, Kato M, Shirotani M, Eizawa H, Ishii K, Lee JD, Takahashi M, Horie M, Takahashi M, Miki S, Aoyama T, Suwa S, Hamasaki S, Ogawa H, Mitsudo K, Nobuyoshi M, Kita T, Kimura T, CREDO-Kyoto Registry Cohort-2 Investigators.
    The American journal of cardiology 114(1) 70-78 2014年07月 [査読有り]
  • Brugada syndrome in spinal and bulbar muscular atrophy.
    Araki A, Katsuno M, Suzuki K, Banno H, Suga N, Hashizume A, Mano T, Hijikata Y, Nakatsuji H, Watanabe H, Yamamoto M, Makiyama T, Ohno S, Fukuyama M, Morimoto S, Horie M, Sobue G
    Neurology 82(20) 1813-1821 2014年05月 [査読有り]
  • A molecular mechanism for adrenergic-induced long QT syndrome.
    Wu J, Naiki N, Ding WG, Ohno S, Kato K, Zang WJ, Delisle BP, Matsuura H, Horie M
    Journal of the American College of Cardiology 63(8) 819-827 2014年03月 [査読有り]
  • A KCNQ1 mutation contributes to the concealed type 1 long QT phenotype by limiting the Kv7.1 channel conformational changes associated with protein kinase A phosphorylation.
    Bartos DC, Giudicessi JR, Tester DJ, Ackerman MJ, Ohno S, Horie M, Gollob MH, Burgess DE, Delisle BP
    Heart rhythm 11(3) 459-468 2014年03月 [査読有り]
  • Efficacy of bepridil to prevent ventricular fibrillation in severe form of early repolarization syndrome.
    Katsuumi G, Shimizu W, Watanabe H, Noda T, Nogami A, Ohkubo K, Makiyama T, Takehara N, Kawamura Y, Hosaka Y, Sato M, Fukae S, Chinushi M, Oda H, Okabe M, Kimura A, Maemura K, Watanabe I, Kamakura S, Horie M, Aizawa Y, Makita N, Minamino T
    International journal of cardiology 172(2) 519-522 2014年03月 [査読有り]
  • A Kir3.4 mutation causes Andersen-Tawil syndrome by an inhibitory effect on Kir2.1.
    Kokunai Y, Nakata T, Furuta M, Sakata S, Kimura H, Aiba T, Yoshinaga M, Osaki Y, Nakamori M, Itoh H, Sato T, Kubota T, Kadota K, Shindo K, Mochizuki H, Shimizu W, Horie M, Okamura Y, Ohno K, Takahashi MP
    Neurology 82(12) 1058-1064 2014年03月 [査読有り]
  • P-pulmonale and the development of atrial fibrillation.
    Hayashi H, Miyamoto A, Kawaguchi T, Naiki N, Xue JQ, Matsumoto T, Murakami Y, Horie M
    Circulation journal : official journal of the Japanese Circulation Society 78(2) 329-337 2014年 [査読有り]
  • QT is longer in drug-free patients with schizophrenia compared with age-matched healthy subjects.
    Fujii K, Ozeki Y, Okayasu H, Takano Y, Shinozaki T, Hori H, Orui M, Horie M, Kunugi H, Shimoda K
    PloS one 9(6) e98555 2014年 [査読有り]
  • Long-term pharmacological therapy of Brugada syndrome: is J-wave attenuation a marker of drug efficacy?
    Hasegawa K, Ashihara T, Kimura H, Jo H, Itoh H, Yamamoto T, Aizawa Y, Horie M
    Internal medicine (Tokyo, Japan) 53(14) 1523-1526 2014年 [査読有り]
  • [Mechanisms for onset and maintenance of atrial fibrillation and its risk factors].
    Horie M
    Nihon rinsho. Japanese journal of clinical medicine 71(1) 29-35 2013年01月 [査読有り]
  • Is More Aggressive Prevention of Coronary Artery Disease Required for Patients With Early Repolarization Syndrome?
    Circ J. 77(6) 1643-1643 2013年
  • LOX-1 ligands containing apolipoprotein B and carotid intima-media thickness in middle-aged community-dwelling US Caucasian and Japanese men.
    Atherosclerosis 229(1) 240-245 2013年
  • Clinical and electrocardiographic characteristics of patients with short QT interval in a large hospital-based population.
    Miyamoto A, Hayashi H, Yoshino T, Kawaguchi T, Taniguchi A, Itoh H, Sugimoto Y, Itoh M, Makiyama T, Xue JQ, Murakami Y, Horie M
    Heart Rhythm 9(1) 66-74 2012年01月 [査読有り]
  • Pediatric Cohort with Short QT Syndrome
    J Am Coll Cardiol 61(11) 1183-1191 2013年
  • Regulatory mechanisms underlying the modulation of GIRK1/GIRK4 heteromeric channels by P2Y receptors
    Pflugers Arch 463(4) 625-633 2012年
  • KCNE3 T4A as the Genetic Basis of Brugada-Pattern Electrocardiogram
    Circ J 76(12) 2763-2772 2012年
  • Regional cooling facilitates termination of spiral-wave reentry through unpinning of rotors in rabbit hearts.
    Heart Rhythm. 9(1) 107-114 2012年
  • The role of fibroblasts in complex fractionated electrograms during persistent/permanent atrial fibrillation implications for electrogram-based catheter ablation.
    Ashihara T, Haraguchi R, Nakazawa K, Namba T, Ikeda T, Nakazawa Y, Ozawa T, Ito M, Horie M, Trayanova NA
    Circulation Research 110(2) 275-285 2012年01月 [査読有り]
  • A novel gain-of-function KCNJ2 mutation associated with short QT syndrome impairs inward rectification of Kir2.1 currents.
    Cardiovascular Research  93(4) 666-673 2012年
  • Connexin 40 mutation associated with a malignant variant of familial progressive heart block type-1.
    Circulation Arrhythmia and Electrophysiology  5(1) 163-172 2012年
  • Dynamicity of the J wave in idiopathic ventricular fibrillation with a special reference to pause-dependent augmentation of the J wave.
    Journal of American College of Cardiology  59(22) 1948-1953 2012年
  • Pharmacotherapeutic determinants for QTc interval prolongation in Japanese patients with mood disorder.
    Pharmacopsychiatry 45(7) 279-283 2012年
  • Time course and prognostic implications of QT interval in patients with coronary artery disease undergoing coronary bypass surgery.
    Kinoshita T, Asai T, Suzuki T, Matsubayashi K, Horie M
    J Cardiovasc Electrophysiol 23(6) 645-649 2012年06月 [査読有り]
  • Chronic heart failure: progress in diagnosis and treatment. Topics: II. Progress in diagnosis: 2. Biomarker
    Nihon Naika Gakkai Zasshi 101(2) 345-53 2012年
  • Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization.
    Circulation: Cardiovascular Genetics 5(3) 344-353 2012年
  • Comparison of long-term outcome after percutaneous coronary intervention versus coronary artery bypass grafting in patients with unprotected left main coronary artery disease (from the CREDO-Kyoto PCI/CABG Registry Cohort-2).
    Am J Cardiol. 110(7) 924-932 2012年
  • Clinical characteristics and risk of arrhythmia recurrences in patients with idiopathic ventricular fibrillation associated with early repolarization.
    Int J Cardiol. 159(3) 238-240 2012年
  • Disease characterization using LQTS-specific induced pluripotent stem cells.
    Cardiovascular Research  95(4) 419-429 2012年
  • Seasonal and circadian distributions of cardiac events in genotyped patients with congenital long QT syndrome.
    Circ J. 76(9) 2112-2118 2012年
  • Prognostic implications of progressive cardiac conduction disease.
    Circ J. 77(1) 60-67 2012年
  • [Angina pectoris: classification and differential diagnosis].
    Yamamoto T, Horie M
    Nihon rinsho. Japanese journal of clinical medicine 69 Suppl 9 9-13 2011年11月 [査読有り]
  • KCN]2変異を伴うAndersen-Tawil症候群の神経生理所見
    臨床神経生理学 39(1) 18-23 2011年
  • Biological variation of brain natriuretic Peptide and cardiac events in stable outpatients with nonischemic chronic heart failure.
    Nishiyama K, Tsutamoto T, Yamaji M, Kawahara C, Fujii M, Yamamoto T, Horie M
    Circ J.  75(2) 341-347 2011年 [査読有り]
  • 循環器疾患における遺伝的背景と発症機序理解のための多面的アプローチ
    循環器内科 70 421-422 2011年
  • Lipocalin-Type Prostaglandin D Synthase Is Associated With Coronary Vasospasm and Vasomotor Reactivity in Response to Acetylcholine.
    Matsumoto T, Eguchi Y, Oda H, Yamane T, Tarutani Y, Ozawa T, Hayashi H, Nakae I, Horie M, Urade Y
    Circ J 75(4) 897-904 2011年 [査読有り]
  • Reciprocal control of HERG stability by Hsp70 and Hsc70 with implication for restoration of LQT2 mutant stability.
    Circ Res 108(4) 458-468 2011年
  • Novel KCNE5 variants are associated with Brugada syndrome and idiopathic ventricular fibrillation.
    Circulation Arrhythmia and Electrophysiology  4(3) 352-361 2011年
  • Prognostic role of high-sensitivity cardiac troponin T in patients with nonischemic dilated cardiomyopathy.
    Kawahara C, Tsutamoto T, Nishiyama K, Yamaji M, Sakai H, Fujii M, Yamamoto T, Horie M
    Circ J 75(3) 656-661 2011年 [査読有り]
  • A Novel KCNJ2 Nonsense Mutation, S369X, Impedes Trafficking and Causes a Limited Form of Andersen-Tawil Syndrome.
    Circulation: Cardiovascular Genetics  4(3) 253-260 2011年
  • Risk determinants in individuals with a spontaneous type 1 Brugada ECG.
    Miyamoto A, Hayashi H, Makiyama T, Yoshino T, Mizusawa Y, Sugimoto Y, Ito M, Xue JQ, Murakami Y, Horie M
    Circulation Journal 75(4) 844-845 2011年 [査読有り]
  • Remission of abnormal conduction and repolarization in the right ventricle after chemotherapy in patients with anterior mediastinal tumor.
    Miyamoto A, Hayashi H, Ito M, Horie M
    J Cardiovasc Electrophysiol.  22(3) 350-350 2011年03月 [査読有り]
  • Angiotensin-converting enzyme inhibition and fibrinolytic balance.
    Matsumoto T, Horie M
    Hypertention Research 34(4) 448-449 2011年04月 [査読有り]
  • Association between brachial-ankle pulse wave velocity and endothelium-dependent and -independent coronary vasomotor function.
    Yoshino T, Nakae I, Matsumoto T, Mitsunami K, Horie M
    Clin Exp Pharmacol Physiol.  38(1) 34-41 2011年01月 [査読有り]
  • Relationship Between Biological Variation in B-Type Natriuretic Peptide and Plasma Renin Concentration in Stable Outpatients With Dilated Cardiomyopathy.
    Nishiyama K, Tsutamoto T, Kawahara C, Yamaji M, Sakai H, Yamamoto T, Fujii M, Horie M
    Circ J.  75(8) 1897-1904 2011年 [査読有り]
  • Phenotypic manifestations of mutations in genes encoding subunits of cardiac potassium channels.
    Circ Res. 109(1) 97-109 2011年
  • Identification and functional characterization of KCNQ1 mutations around the exon7-intron7 junction affecting the splicing process.
    Tsuji-Wakisaka K, Akao M, Ishii TM, Ashihara T, Makiyama T, Ohno S, Toyoda F, Dochi K, Matsuura H, Horie M
    BBA - Molecular Basis of Disease  1812(11) 1452-1459 2011年11月 [査読有り]
  • Heritability of early repolarization: A population-based study.
    Circulation Cardiovascular Genetics  4(5) e20 2011年
  • Clinical characteristics and long-term prognosis of vasospastic angina patients who survived out-of-hospital cardiac arrest: multicenter registry study of the Japanese Coronary Spasm Association.
    Circ Arrhythm Electrophysiol. 4(3) 295-302 2011年
  • Prognostic value of serial measurements of highly sensitive cardiac troponin I in stable outpatients with nonischemic chronic heart failure.
    Kawahara C, Tsutamoto T, Sakai H, Nishiyama K, Yamaji M, Fujii M, Yamamoto T, Horie M
    American Heart Journal 162(4) 639-645 2011年10月 [査読有り]
  • Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated with Early Repolarization.
    Circulation: Arrhythmia and Electrophysiology 4(6) 874-881 2011年
  • Clinical characteristics and outcomes of Japanese women undergoing coronary revascularization therapy.
    Circulation Journal 75(6) 1358-1367 2011年
  • Effect of atorvastatin vs. rosuvastatin on cardiac sympathetic nerve activity in non-diabetic patients with dilated cardiomyopathy.
    Circulation Journal  75(9) 2160-2166 2011年
  • Carvedilol, a non-selective β-with α1-blocker is effective in long QT syndrome type2.
    Journal of Arrhythmia  27 324-331 2011年
  • Long-term safety and efficacy of sirolimus-eluting stents versus bare-metal stents in real world clinicalpractice in Japan.
    Cardiovascular Intervention and Therapeutics 26 234-245 2011年
  • 遺伝子異常と不整脈
    臨床と研究 87(1) 98-101 2010年
  • QTが長ければQT延長症候群か?
    medicina 47(1) 66-68 2010年
  • デスモゾーム病としての不整脈源性右室心筋症-デスモゾーム分子遺伝子異常
    医学のあゆみ 232(5) 588-592 2010年
  • 運動中の心臓性突然死:成人の不整脈
    心電図 30(s-2) 13-24 2010年
  • 自動体外式除細動器による救命後に下肢切断を要したが心臓リハビリテーションにより回復した2症例。
    心臓 42(6) 764-770 2010年
  • 高血圧治療薬としてのアンジオテンシンⅡ受容体拮抗薬とカルシウム拮抗薬の血管炎症および酸化ストレスに及ぼす影響。
    Prog.Med. 30(2) 469-472 2010年
  • 日本人の心房細動における治療戦略の最新状況
    Trans BEAT 7 12-14 2010年
  • 高血圧と不整脈:高血圧の治療によって不整脈発症の予防は可能か?
    Life Style Medicine 4 322-326 2010年
  • 遺伝性不整脈の診断と治療におけるiPS細胞利用の可能性。
    最新医学 139-145 2010年
  • カテコラミン誘発性多形性心室頻拍を疑う患者における遺伝子変異の検討-心筋リアノジン受容体について―Mutations of the cardiac ryanodine recepter gene in Catecholaminergic Polymorphic Ventricular Tachycardia
    心電図 30 298-305 2010年
  • 日本人の脳卒中、心筋梗塞、腎臓病に対するリスク因子の寄与度の違い:わが国の疫学研究から。
    Mebio 27(10) 30-44 2010年
  • QTc prolongation and antipsychotic medications in a sample of 1017 patients with schizophrenia.
    Progress in Neuro-Psychopharmacology & Biological Psychiatry  34(2) 401-405 2010年
  • Prognostic role of highly sensitive cardiac troponin I in patients with systolic heart failure
    Tsutamoto T, Kawahara C, Nishiyama K, Yamaji M, Fujii M, Yamamoto T, Horie M
    Am Heart J 159(1) 63-67 2010年01月 [査読有り]
  • Comparison of the long-term effects of candesartan and olmesartan on plasma angiotensin II and left ventricular mass index in patients with hypertension.
    Tsutamoto T, Nishiyama K, Yamaji M, Kawahara C, Fujii M, Yamamoto T, Horie M
    Hypertens Res. 33(2) 118-122 2010年02月 [査読有り]
  • Clinical characteristics and genetic background of congenital long QT syndrome diagnosed in fetal, neonatal and infantile life. A nation-wide questionnaire survey in Japan.
    Circ Arrhythm Electrophysiol.  3(1) 10-17 2010年
  • P-wave features with marked left atrial overload for predicting development of atrial fibrillation
    Heart Rhythm  7(3) 289-94 2010年
  • KCNE2 modulation of KV4.3 current and its potential role in fatal rhythm disorders.
    Heart Rhythm 7(2) 199-205 2010年
  • High prevalence of early repolarization in short QT syndrome.
    Heart Rhythm 7(5) 647-652 2010年
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  • Functional compartmentalization of ATP is involved in angiotensin II-mediated closure of cardiac ATP-sensitive K+ channels.
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    Japanese Journal Physiology 40 479-490 1990年
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    Japanese Circulation Journal 54 478-486 1990年
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    American Journal of Physiology 253 H210-H214 1987年
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    日本内科学会誌 9 41-45 1985年
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    Acta Medica Scandinavica 694 83-94 1985年
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    最新医学 39 1071-1073 1984年
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    Angiology 34 553-560 1983年
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    American Journal of Cardiology 47 539-546 1981年
  • Diltiazem-induced decrease of exercise-elevated pulmonary arterial diastolic pressure in hypertrophic cardiomyopathy patients.
    American Heart Journal 102 789-790 1981年

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  • Brugada症候群と遺伝子異常 臨床心臓病学
    文光堂 2006年
  • 頻脈性不整脈を診る・治す QT延長症候群 病態・分類・検査. 新・心臓病診療プラクティス 7 心電図で診る・治す
    文光堂 2006年
  • BNPと心不全―エビデンスを中心に―. 新BNPと日常臨床―心機能異常の早期発見のために―
    南江堂 2005年
  • 不整脈2003 Medical Topics Series : QT延長症候群と遺伝子異常
    メディカルレビュー社 2003年
  • 不整脈診療ガイダンス : QT延長症候群の分類と遺伝子異常について最近の知見を教えてください
    メジカルビュー社 2003年
  • 新パッチクランプ実験技術法 : 細胞内灌流法
    吉岡書店 2003年
  • 最新医学 別冊 ABC15 心房細胞
    最新医学社 2003年
  • 今月の治療 VOL.11増刊 循環器疾患治療スタンダード2004-2005 : 不整脈治療薬の催不整脈作用
    総合医学社 2003年
  • ナースのための循環器科 : 心疾患を知る-不整脈
    メディカ出版 2003年
  • QT延長症候群 : 循環器疾患最新の治療2002-2003
    南江堂 2002年

MISC

  • A SCN5A Variant Associated with Drug Induced Brugada Type ECG(和訳中)
    藍 智彦, 三井田 孝, 堀江 稔
    臨床病理 65(補冊) 268-268 2017年10月
  • Timothy症候群亜型におけるCACNA1C新規遺伝子変異の同定と電気生理学的検討
    小澤淳一, 小澤淳一, 小澤淳一, 大野聖子, 大野聖子, 鈴木博, 齋藤昭彦, 松浦博, 堀江稔
    日本小児科学会雑誌 121(8) 1426‐1427-1427 2017年08月
  • QT延長を伴うカテコラミン誘発多形性心室頻拍(CPVT)の3例
    西藤陽, 二宮由美子, 田中裕治, 塗木徳人, 大野聖子, 堀江稔, 吉永正夫
    日本小児科学会雑誌 121(7) 1267‐1268-1268 2017年07月
  • Timothy症候群亜型におけるCACNA1C新規遺伝子変異の同定と電気生理学的検討
    小澤 淳一, 大野 聖子, 鈴木 博, 齋藤 昭彦, 松浦 博, 堀江 稔
    日本小児科学会雑誌 121(8) 1426-1427 2017年08月
  • 一般健常男性における喫煙習慣・禁煙期間と潜在性動脈硬化指標との関連:滋賀動脈硬化疫学研究SESSA
    久松隆史, 久松隆史, 久松隆史, 三浦克之, 有馬久富, 門田文, 門脇紗也佳, 鳥居さゆ希, 鈴木仙太朗, 宮川尚子, 佐藤敦, 藤吉朗, 大久保孝義, アボット ロバート, 関川暁, 堀江稔, 上島弘嗣
    日本動脈硬化学会総会・学術集会プログラム・抄録集(Web) 49th 112 (WEB ONLY)-112 2017年06月
  • 心房細動患者におけるアピキサバンの母集団薬物動態解析
    山根拓也, 上島智, 平大樹, 木村悠馬, 藤井亮, 冨塚知歩, 田淵陽平, 伊藤英樹, 大野聖子, 小澤友哉, 堀江稔, 寺田智祐, 桂敏也
    医療薬学フォーラム講演要旨集 25th 233 2017年06月
  • 心房細動患者におけるアピキサバンの血中濃度に及ぼす薬物動態関連遺伝子多型の影響
    上島智, 平大樹, 堀江稔, 寺田智祐, 桂敏也
    臨床薬理の進歩(38) 104‐112-112 2017年06月
    アピキサバンの錠剤を内服した成人心房細動(AF)患者44例(男性36例、女性8例、38.3〜80.1歳)を対象とした。データ数は70点で、アピキサバンの血中濃度の中央値は137ng/mLであった。薬物動態関連遺伝子多型のSNPを解析し、いずれの遺伝子多型もHardy-Weinberg平衡が成立していることを確認した。ABCB1 2677G/TまたはG/Aを保有する患者は、G/Gを保有する患者と比べてアピキサバンのC/D比がわずかに低くなった。ABCG2 421A/A遺伝子を保有する患者は、C/Cを保有する患者と比較してアピキサバンのC/D比が1.55倍有意に高くなった。CYP3A5*1/*3または*3/*3を保有する患者は、*1/*1を保有する患者と比較してアピキサバンのC/D比がそれぞれ1.67倍、1.60倍有意に高くなった。アピキサバンのC/D比は、年齢、Scr、eGFRと有意な相関を示し、eGFRが増加するに伴ってC/D比は低くなった。CYP3A5*3またはABCG2 421A/A保有者、eGFRがアピキサバンのC/D比の変動要因として検出した。
  • 産科危機的出血に伴う搬送のタイミングに苦慮した1例
    川内 華佳, 吉永 洋輔, 大塚 由花, 松浦 寛子, 澁谷 剛志, 堀江 稔, 村上 充剛
    日本周産期・新生児医学会雑誌 53(2) 554-554 2017年06月
  • 表現型・治療方針が異なったSCN5A compound mutationの1家系
    星野健司, 小川潔, 菱谷隆, 河内貞貴, 斎藤千徳, 馬場俊輔, 石川悟, 新田順一, 牧山武, 大野聖子, 堀江稔
    Therapeutic Research 38(4) 362‐365-365 2017年04月
    症例は24歳女性で、中学1年生時の学校心臓検診でQT延長を指摘され、受診した。初診時心電図ではQT=516ms、QTc=520msと著明な延長を認め、運動時のQT短縮は良好であった。SCN5Aのcompound mutation transはE1784K&V1098Lの兄妹例を経験した。異なる表現型を呈したが、表現型に対応する治療により良好な経過を取っている。compound mutationの意義、性差による表現型、重症度の差異を考える上で重要と考えられた。
  • 心臓突然死の遺伝的背景(Copy Number Variations of SCN5A in Brugada Syndrome)
    園田 桂子, 大野 聖子, 市川 麻理, 服部 哲久, 伊藤 英樹, 牧山 武, 堀江 稔
    日本循環器学会学術集会抄録集 81回 SY09-3 2017年03月
  • 経カテーテル的大動脈弁置換術(TAVI)を施行した2例
    山本孝, 八木典章, 松本祐一, 木村紘美, 酒井宏, 堀江稔, 森本政憲, 寺田真也, 坂倉玲欧, 木下武, 鈴木友彰, 浅井徹, 水野隆芳, 北川裕利
    滋賀医学 39 106-106 2017年03月
  • Short‐coupled variant of torsade de pointesの臨床像と遺伝学的背景
    藤居祐介, 伊藤英樹, 大野聖子, 堀江稔, BLANCARD Malorie, GUICHENEY Pascale, 青木寿明, 中川義久, 山本聖, 松井由美恵, 大久保公恵, 渡辺一郎
    滋賀医学 39 73-73 2017年03月
  • 心臓突然死の遺伝的背景(Genetic Background of Congenital Long QT Syndrome Diagnosed in Infancy and Comparison of Their Gene Mutations with Those in SIDS)
    堀米 仁志, 吉永 正夫, 住友 直方, 林 立申, 加藤 愛章, 牛ノ濱 大也, 田内 宣生, 大野 聖子, 清水 渉, 堀江 稔, 長嶋 正實
    日本循環器学会学術集会抄録集 81回 SY09-6 2017年03月
  • A Novel Transport Refractory Mutation in KCNH2 Identified in Symptomatic Long QT Syndrome Patients(和訳中)
    福本 大介, 大野 聖子, 和田 悠子, 藤居 祐介, 市川 麻理, 福山 恵, 伊藤 英樹, 松浦 博, 堀江 稔
    日本循環器学会学術集会抄録集 81回 PJ-028 2017年03月
  • Rare Single Nucleotide Polymorphism of SCN10A in Patients with Inherited Primary Arrhythmia Syndromes(和訳中)
    福山 恵, 大野 聖子, 市川 麻理, 牧山 武, 堀江 稔
    日本循環器学会学術集会抄録集 81回 PJ-029 2017年03月
  • 遺伝性不整脈の日本人コホートにおける遺伝的背景と発症メカニズムの検討
    堀江 稔
    先進医薬研究振興財団研究成果報告集 2016年度 224-228 2017年03月
  • Genetic Variants of Alcohol-Metabolizing Enzymes in Brugada Syndrome: Insights into Syncope after Drinking Alcohol(和訳中)
    呉 き, 林 秀樹, 牧山 武, 堀江 稔
    日本循環器学会学術集会抄録集 81回 PJ-031 2017年03月
  • Six-Month Follow-up after the ExTRa Mappingguided Non-Passive Activation Area Ablation for Non-Paroxysmal Atrial Fibrillation(和訳中)
    芦原 貴司, 坂田 憲祐, 小澤 友哉, 土谷 健, 原口 亮, 中沢 一雄, 堀江 稔
    日本循環器学会学術集会抄録集 81回 PJ-459 2017年03月
  • ラミノパチー患者に対する両室再同期療法は心不全予後を改善させるか?
    中島健三郎, 相庭武司, 西内英, 牧山武, 尾上健児, 鎌倉令, 和田暢, 石橋耕平, 岡村英夫, 大野聖子, 宮本恵宏, 斎藤能彦, 堀江稔, 清水渉, 草野研吾
    日本心臓病学会学術集会(Web) 65th ROMBUNNO.O‐030 (WEB ONLY)-030 2017年09月
  • 当院における超緊急帝王切開12例の検討とシステム構築の現状
    澁谷 剛志, 吉永 洋輔, 大塚 由花, 川内 華佳, 松浦 寛子, 渡辺 昭夫, 加藤 雅史, 堀江 稔, 村上 充剛
    日本産科婦人科学会雑誌 69(2) 772-772 2017年02月
  • カテコラミン誘発性多形性心室頻拍の重症化に関与する遺伝な修飾因子の解明
    長谷川奏恵, 長谷川奏恵, 大野聖子, 大野聖子, 伊藤英樹, 芦原貴司, 牧山武, 堀江稔
    心臓 48(12) 1446-1446 2016年12月
  • 著明な左室収縮能低下と徐脈を認めplakophilin2遺伝子変異による不整脈原性右室心筋症と診断した1例
    高橋友香里, 久保亨, 越智友梨, 高橋有紗, 宮川和也, 野口達哉, 弘田隆省, 山崎直仁, 堀江稔, 北岡裕章
    日本心臓病学会学術集会(Web) 65th ROMBUNNO.P‐068 (WEB ONLY)-068 2017年09月
  • 重症新生児仮死児の高次医療機関への迅速な搬送を目指した取り組み
    藤田 基資, 野村 智章, 西村 直人, 釜江 智佳子, 金井 貴志, 中川 紀子, 滝沢 真理, 川内 華佳, 渋谷 剛志, 加藤 雅史, 吉永 洋輔, 堀江 稔, 村上 充剛, 黒木 康富
    防衛衛生 64(別冊) 48-48 2016年12月
  • QT延長症候群女性における周産期リスクの検討
    神谷千津子, 石橋耕平, 石橋耕平, 宮崎文, 坂口平馬, 和田暢, 宮本康二, 野田崇, 山内俊史, 伊藤英樹, 大野聖子, 本村秀樹, 小川禎治, 後藤浩子, 南孝臣, 八木原伸江, 渡部裕, 長谷川奏恵, 寺沢彰浩, 三上仁, 荻野佳代, 中野由紀子, 今城沙都, 福嶋遥佑, 都築慶光, 朝倉こう子, 吉松淳, 白石公, 宮本恵宏, 安田聡, 堀江稔, 清水渉, 清水渉, 草野研吾, 相庭武司
    日本人類遺伝学会大会プログラム・抄録集 62nd 333 2017年
  • 今,診断を見直す 血中BNP値やNT‐proBNP値を用いた心不全診療の留意点
    蔦本尚慶, 奥山雄介, 福山恵, 河原千穂, 酒井宏, 堀江稔
    循環plus 17(1) 10‐12-12 2016年10月
  • 脳性ナトリウム利尿ペプチド(BNP),N末端プロBNP(NT‐proBNP)の最新情報
    蔦本尚慶, 市川麻理, 河原千穂, 酒井宏, 堀江稔
    日本心不全学会学術集会プログラム・抄録集 21st 249 2017年
  • 滋賀医科大学附属病院におけるアミオダロンによる間質性肺炎
    林秀樹, 伊藤英樹, 芦原貴司, 小澤友哉, 加藤浩一, 藤居祐介, 坂田憲祐, 堀江稔
    Progress in Medicine 36 439‐442 2016年04月
  • 日本循環器学会/日本小児循環器学会合同ガイドライン 2016年版 学校心臓検診のガイドライン
    住友 直方, 石川 広己, 泉田 直己, 市田 蕗子, 岩本 眞理, 笠巻 祐二, 久賀 圭祐, 土井 庄三郎, 中西 敏雄, 馬場 礼三, 檜垣 高史, 堀米 仁志, 三谷 義英, 武者 春樹, 吉永 正夫, 阿部 勝己, 鮎沢 衛, 牛ノ濱 大也, 太田 邦雄, 加藤 愛章, 加藤 太一, 澤田 博文, 鉾碕 竜範, 葭葉 茂樹, 新 博次, 小川 俊一, 奥村 謙, 筒井 裕之, 長嶋 正實, 丹羽 公一郎, 平山 篤志, 堀江 稔, 日本循環器学会,日本小児循環器学会,一般社団法人日本循環器学会ガイドライン委員会
    循環器病ガイドシリーズ 2016(学校心臓検診のガイドライン) i-80 2016年11月
  • 日本循環器学会/日本小児循環器学会合同ガイドライン【ダイジェスト版】 2016年版 学校心臓検診のガイドライン
    住友 直方, 石川 広己, 泉田 直己, 市川 蕗子, 岩本 眞理, 笠巻 祐二, 久賀 圭祐, 土井 庄三郎, 中西 敏雄, 馬場 礼三, 檜垣 高史, 堀米 仁志, 三谷 義英, 武者 春樹, 吉永 正夫, 阿部 勝己, 鮎沢 衛, 牛ノ濱 大也, 太田 邦雄, 加藤 愛章, 加藤 太一, 澤田 博文, 鉾碕 竜範, 葭葉 茂樹, 新 博次, 小川 俊一, 奥村 謙, 筒井 裕之, 長嶋 正實, 丹羽 公一郎, 平山 篤志, 堀江 稔, 日本循環器学会,日本小児循環器学会
    循環器病ガイドシリーズ 2016(学校心臓検診のガイドライン) 81-148 2016年11月
  • ホルター心電図で2方向性心室頻拍を認めたアンダーセン・タウィル症候群の1例
    大国 千尋, 清水 祥子, 木村 紘美, 藤澤 義久, 堀江 稔, 宮平 良満, 九嶋 亮治
    医学検査 65(6) 679-684 2016年11月
    アンダーセン・タウィル症候群(Andersen-Tawil syndrome;ATS)は、(1)U波を伴う心室性不整脈、(2)周期性四肢麻痺、(3)外表小奇形を3徴とするまれな遺伝性疾患である。内向き整流性カリウムチャネルであるKir2.1蛋白をコードしているKCNJ2遺伝子の変異が原因で発症する。心電図所見としてQU延長を伴う著明なU波と頻発する心室期外収縮(PVC)、2方向性心室頻拍を認め、治療にはIc群抗不整脈薬であるフレカイニドの有用性が報告されている。症例は50代女性、ATSの3徴全てを満たし、QU延長(723msec)を伴う著明なU波、PVC頻発を認め、遺伝子検索にてKCNJ2遺伝子変異陽性であった。ホルター心電図では総心拍の24%のPVC、2方向性心室頻拍を認め、フレカイニドの導入により9%までPVCが減少、動悸症状も改善した。ATSでは、増高したU波や2方向性心室頻拍が重要な所見となるため、心電図検査、ホルター心電図の解析では、QU時間、U波高、U波幅、PVCの極性などの情報にも着目する必要がある。(著者抄録)
  • Desmosome2遺伝子に非常に稀少な1塩基置換2座を認めた不整脈原性右室心筋症(ARVC)の1例
    利根川 玲奈, 中島 崇智, 高橋 弘武, 村上 彰通, 仲野 陽介, 大野 聖子, 和田 悠子, 宮本 敬史, 堀江 稔, 武藤 誠
    日本内科学会関東地方会 628回 35-35 2016年11月
  • 小児QT延長症候群:LQT2は発症年齢が高いが重症例が多い
    小澤淳一, 大野聖子, 伊藤英樹, 堀江稔, 大野聖子, 小澤淳一, 牧山武
    滋賀医学 38 71 2016年03月
  • 小児QT延長症候群 LQT2は発症年齢が高いが重症例が多い
    小澤 淳一, 大野 聖子, 伊藤 英樹, 堀江 稔, 牧山 武
    滋賀医学 38 71-71 2016年03月
  • 日本循環器学会/日本TDM学会合同ガイドライン(2013-2014年度合同研究班報告)【ダイジェスト版】 2015年版 循環器薬の薬物血中濃度モニタリングに関するガイドライン
    青沼 和隆, 志賀 剛, 新 博次, 池田 隆徳, 市田 蕗子, 上野 和行, 越前 宏俊, 栄田 敏之, 清水 渉, 菅原 満, 土下 喜正, 土岐 浩介, 戸塚 恭一, 萩原 誠久, 長谷川 純一, 林 秀晴, 平尾 見三, 前田 頼伸, 松本 直樹, 渡邉 英一, 笠井 英史, 篠原 徳子, 杉山 篤, 鈴木 敦, 住友 直方, 関口 幸夫, 高橋 尚彦, 野上 昭彦, 橋口 正行, 平田 純生, 松本 宜明, 湯川 栄二, 伊藤 宏, 井上 博, 大江 透, 篠崎 公一, 田中 一彦, 本間 真人, 堀江 稔, 三浦 崇則, 日本循環器学会,日本TDM学会
    TDM研究 33(3) 123-157 2016年09月
  • AMIによる難治性VFに対し病病連携とROSC後の集学的治療により社会復帰した一例
    田中 智基, 村尾 淳司, 喜多 理香, 北村 直美, 松下 美季子, 八木 典章, 山本 孝, 堀江 稔, 藤野 和典, 田畑 貴久, 江口 豊, 岡林 旅人
    滋賀医学 38 104-105 2016年03月
  • 日本循環器学会/日本TDM学会合同ガイドライン(2013-2014年度合同研究班報告)【ダイジェスト版】 2015年版 循環器薬の薬物血中濃度モニタリングに関するガイドライン
    青沼 和隆, 志賀 剛, 新 博次, 池田 隆徳, 市田 蕗子, 上野 和行, 越前 宏俊, 栄田 敏之, 清水 渉, 菅原 満, 土下 喜正, 土岐 浩介, 戸塚 恭一, 萩原 誠久, 長谷川 純一, 林 秀晴, 平尾 見三, 前田 頼伸, 松本 直樹, 渡邉 英一, 笠井 英史, 篠原 徳子, 杉山 篤, 鈴木 敦, 住友 直方, 関口 幸夫, 高橋 尚彦, 野上 昭彦, 橋口 正行, 平田 純生, 松本 宜明, 湯川 栄二, 伊藤 宏, 井上 博, 大江 透, 篠崎 公一, 田中 一彦, 本間 真人, 堀江 稔, 三浦 崇則, 日本循環器学会,日本TDM学会
    TDM研究 33(3) 123-157 2016年09月
  • 当院における心臓手術後リハビリテーション進行の検討 成長期に入った当院における今後の課題
    飛田 良, 澁川 武志, 木下 妙子, 前川 昭次, 川口 民郎, 浅井 徹, 堀江 稔
    心臓リハビリテーション 22(1) 44-50 2016年06月
    【目的】導入期から成長期に入った当院における心臓手術後リハビリテーションの進行状況を把握し、今後の課題を検討すること。【方法】平成24年4月から平成25年8月までの当院心臓血管外科手術症例469例を緊急群と待機群で各々歩行獲得状況が早期自立群、順調群、遅延群、非自立群の4群に分け、日本循環器学会ガイドラインが示すものと比較検討した。【結果】待機群に比べ緊急群の術後歩行自立日数は有意に延長していた。術後歩行獲得状況は、待機群でガイドラインよりも早期自立群が多く、緊急群では、ガイドラインよりも非自立群が多く、大血管手術が多数を占め、肺炎や長期挿管などの呼吸器由来が主な遅延理由であった。【結論】当院における今後の課題は、ハイリスク症例への効果的介入であり、早期離床や一般的な運動療法だけでなく、CCUや一般病棟での多職種での関わりをより深め、術後早期からの効果的介入が重要になると考える。(著者抄録)
  • 心房細動合併収縮不全の1例 Rate control? rhythm control?それとも…
    酒井 宏, 冨田 行則, 小澤 友哉, 山本 孝, 堀江 稔
    滋賀医学 38 109-109 2016年03月
  • 滋賀医科大学附属病院におけるアミオダロンによる間質性肺炎
    林 秀樹, 伊藤 英樹, 芦原 貴司, 小澤 友哉, 加藤 浩一, 藤居 祐介, 坂田 憲祐, 堀江 稔
    Progress in Medicine 36(Suppl.1) 439-442 2016年04月
    アミオダロンによる間質性肺炎について検討した。アミオダロン使用例のうち間質性肺炎と診断された患者を抽出した。アミオダロンを使用した448例中、5例(男性3名、女性2名、平均72±5歳)で間質性肺炎を認めた。KL-6は多くの症例が正常範囲内であったが、間質性肺炎5例中2例は正常値以上であった。間質性肺炎3例で白血球数、また4例でCRP値が正常値以上であった。AST値、ALT値ともに正常値以上のアミオダロン使用例はいたが、間質性肺炎5例では正常範囲内であった。また、総ビリルビン値、直接ビリルビン値が正常値以上のアミオダロン使用例もいた。膵炎マーカーのアミラーゼが正常値以上のアミオダロン使用例もいた。TSH値、fT3値、fT4値が正常値以上のアミオダロン使用例がいた。
  • 慢性心房細動に治療標的となるような定在ローターは存在するか? ExTRa Mappingによる臨床的観察研究
    坂田 憲祐, 芦原 貴司, 小澤 友哉, 土谷 健, 原口 亮, 稲田 慎, 中沢 一雄, 堀江 稔
    心電図 36(Suppl.1) S-1 2016年02月
  • 【循環器疾患と突然死】 遺伝性不整脈と突然死
    堀江 稔
    循環器内科 79(2) 95-101 2016年02月
  • 先天性QT延長症候群におけるmicrovolt T wave alternans
    林 秀樹, 大野 聖子, 清水 祥子, 藤澤 義久, 泉 裕美, 石垣 多佳子, 西川 達也, 大国 千尋, 堀江 稔
    心電図 36(Suppl.1) S-1 2016年02月
  • 慢性心房細動アブレーションにおけるイノベーション実現に向けたin silicoの挑戦 ExTRa Mappingの開発
    芦原 貴司, 坂田 憲祐, 小澤 友哉, 土谷 健, 原口 亮, 稲田 慎, 中沢 一雄, 堀江 稔
    心電図 36(Suppl.1) S-1 2016年02月
  • Clinical efficacy of thrombus aspiration on 5-year clinical outcomes in patients with ST-segment elevation acute myocardial infarction undergoing percutaneous coronary intervention
    Hiroki Watanabe, Hiroki Shiomi, Kenji Nakatsuma, Takeshi Morimoto, Tomohiko Taniguchi, Yutaka Furukawa, Yoshihisa Nakagawa, Minoru Horie, Takeshi Kimura, Takeshi Kimura, Ryuzo Sakata, Akira Marui, Mitsuo Matsuda, Hirokazu Mitsuoka, Masahiko Onoe, Yoshihisa Nakagawa, Kazuo Yamanaka, Hisayoshi Fujiwara, Yoshiki Takatsu, Nobuhisa Ohno, Ryuji Nohara, Tomoyuki Murakami, Teruki Takeda, Masakiyo Nobuyoshi, Masashi Iwabuchi, Michiya Hanyu, Ryozo Tatami, Tsutomu Matsushita, Manabu Shirotani, Noboru Nishiwaki, Toru Kita, Yutaka Furukawa, Yukikatsu Okada, Hiroshi Kato, Hiroshi Eizawa, Katsuhisa Is, Masaru Tanaka, Shogo Nakayama, Jong Dae Lee, Akira Nakano, Takaaki Koshiji, Koichi Morioka, Akinori Takizawa, Mitsuomi Shimamoto, Fumio Yamazaki, Masaaki Takahashi, Junichiro Nishizawa, Minoru Horie, Hiroyuki Takashima, Takashi Tamura, Masaki Aota, Mamoru Takahashi, Takafumi Tabata, Chuwa Tei, Shuichi Hamasaki, Yutaka Imoto, Hiroyuki Yamamoto, Hirofumi Kambara, Osamu Doi, Katsuhiko Matsuda, Masafumi Nara, Kazuaki Mitsudo, Kazushige Kadota, Tatsuhiko Komiya, Shinji Miki, Tetsu Mizoguchi, Hiroyuki Nakajima, Hisao Ogawa, Seigo Sugiyama, Michio Kawasuji, Syuji Moriyama, Ryuichi Hattori, Takeshi Aoyama, Makoto Araki, Satoru Suwa, Keiichi Tanbara, Kumiko Kitagawa, Misato Yamauchi, Naoko Okamoto, Yumika Fujino, Saori Tezuka, Asuka Saeki, Miya Hanazawa, Yuki Sato, Chikako Hibi, Hitomi Sasae, Emi Takinami, Yuriko Uchida, Yuko Yamamoto, Satoko Nishida, Mai Yoshimoto, Sachiko Maeda, Izumi Miki, Saeko Minematsu, Mitsuru Abe, Hiroki Shiomi, Tomohisa Tada, Junichi Tazaki, Yoshihiro Kato, Mamoru Hayano
    Journal of the American Heart Association 4 2015年06月
    © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell. BACKGROUND: Adjunctive thrombus aspiration (TA) during primary percutaneous coronary intervention (PCI) was reported to promote better coronary and myocardial reperfusion. However, long-term mortality benefit of TA remains controversial. The objective of this study is to investigate the clinical impact of TA on long-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary PCI. METHODS AND RESULTS: The CREDO-Kyoto AMI Registry is a large-scale cohort study of acute myocardial infarction patients undergoing coronary revascularization in 2005-2007 at 26 hospitals in Japan. Among 5429 patients enrolled in the registry, the current study population consisted of 3536 patients who arrived at the hospital within 12 hours after the symptom onset and underwent primary PCI. Clinical outcomes were compared between the 2 patient groups with or without TA. During primary PCI procedures, 2239 out of 3536 (63%) patients underwent TA (TA group). The cumulative 5-year incidence of all-cause death was significantly lower in the TA group than in the non-TA group (18.5% versus 23.9%, log-rank P < 0.001). After adjusting for confounders, however, the risk for all-cause death in the TA group was not significantly lower than that in the non-TA group (hazard ratio: 0.90, 95% CI: 0.76 to 1.06, P=0.21). The adjusted risks for cardiac death, myocardial infarction, stroke, and target-lesion revascularization were also not significantly different between the 2 groups. CONCLUSIONS: Adjunctive TA during primary PCI was not associated with better 5-year mortality in STEMI patients.
  • Genetic basis of early repolarization syndrome
    Minoru Horie, Keiko Sonoda, Seiko Ohno
    J Wave Syndromes: Brugada and Early Repolarization Syndromes 77-90 2016年01月
    © Springer International Publishing Switzerland 2016. Among patients with idiopathic ventricular fibrillation (IVF), we experienced significantly higher prevalence of early repolarization (ER), which had been considered as a benign ECG finding in the past. In addition, recurrence of fatal ventricular arrhythmia was associated with the presence of ER. In analogy to ER seen in Brugada syndrome (BS), recently, a novel concept for J-wave syndrome (JWS) has been proposed by Dr. Antzelevitch and Dr. Yan, which includes both BS and ER syndrome (ERS). Indeed, there are several clinical similarities between them regarding (1) presence of familial cases, (2) male predominance, (3) predominant VF occurrence in night, (4) bradycardia-induced augmentation of J-point elevation, (5) reduction or elimination of J-point elevation during exercise or atrial fibrillation, and (6) pharmacological usefulness of isoproterenol and quinidine. From the point of genetic basis, there reported several candidate genes responsible for ERS, most of which are overlapped with those associated with Brugada syndrome. This chapter will mainly focus on the genetic background of ERS and discuss its similarity and difference to that in BS.
  • Novel SCN10A variants associated with Brugada syndrome
    Megumi Fukuyama, Seiko Ohno, Seiko Ohno, Seiko Ohno, Takeru Makiyama, Minoru Horie
    Europace 18 905-911 2016年01月
    © The Author 2015. Aims The expression of sodium channel Nav1.8 in cardiac nervous systems has been identified, and variants of SCN10A that encodes Nav1.8 contribute to the development of Brugada syndrome (BrS) by modifying the function of Nav1.5 or directly reducing the sodium current. The aim of this study was to identify the frequency of SCN10A mutations in Japanese patients with BrS and to compare the phenotypical differences between patients with BrS and those who have other BrScausative genes. Methods and results This study involved 240 Japanese probands who were clinically suspected with BrS and were negative for mutations in major BrS-related genes.We screened for the SCN10A gene using a high-resolution melting method and direct sequencing. In addition, we compared the clinical characteristics among the probands with gene mutations in SCN10A, 6 probands with CACNA1C and 17 probands with SCN5A.We identified six SCN10A variant carriers (2.5%): W189R, R844H (in two unrelated probands), N1328K, R1380Q, and R1863Q. Fivewere male. Fourwere symptomatic: one died following sudden cardiopulmonary arrest at age 35, one suffered ventricular fibrillation, and two had recurrent syncope. Compared with BrS patients carrying SCN5A or CACNA1C mutations, although there were no significant differences among them, symptomatic patients in the SCN10A group tended to be older than those in the other gene groups. Conclusion In six BrS probands who carried SCN10Avariants, most experienced severe arrhythmic attacks. It is of clinical importance to screen SCN10A mutations in BrS, although the functional significance of these variants remains unclear.
  • Impact of Updated Diagnostic Criteria for Long QT Syndrome on Clinical Detection of Diseased Patients: Results From a Study of Patients Carrying Gene Mutations
    Kenshi Hayashi, Tetsuo Konno, Noboru Fujino, Hideki Itoh, Yusuke Fujii, Yoko Imi-Hashida, Hayato Tada, Toyonobu Tsuda, Yoshihiro Tanaka, Takekatsu Saito, Hidekazu Ino, Masa aki Kawashiri, Kunio Ohta, Minoru Horie, Masakazu Yamagishi
    JACC: Clinical Electrophysiology 2 279-287 2016年01月
    © 2016 American College of Cardiology Foundation Objectives In this study, we scored patients with long QT syndrome (LQTS) according to the different Schwartz diagnostic criteria from 1993, 2006, and 2011, and to examine the validation of the criteria in relevance to the frequency of LQTS-related gene mutation. Background Although updated diagnostic criteria have been used in clinical settings, few data exist regarding their impact on the diagnosis of LQTS. Methods We used a cohort of 132 patients who presented with prolonged QTc intervals and/or abnormal clinical history in cardiac screening and who underwent exercise stress testing. LQTS scores of ≥3.5 points according to the 2006 and the 2011 criteria were considered to indicate a high probability of LQTS, as opposed to the 4 points used by the 1993 criteria. The 2011 criteria were updated by adding the evaluation of the recovery phase of exercise. Results The 2011 criteria significantly increased the number of high probability patients (n = 62) compared with the 1993 criteria (n = 32; p = 0.0002) or the 2006 criteria (n = 36; p = 0.0014). The percentage of mutation carriers in those with an intermediate score, which was rather high using the 1993 (53%) and 2006 criteria (53%), was greatly reduced with the 2011 criteria (15%, p = 0.0014 vs. the 1993 criteria, and p = 0.0013 vs. the 2006 criteria). Among 54 mutation carriers, the 1993, the 2006, and the 2011 criteria identified a high probability of carriers in 25 patients (46% sensitivity and 91% specificity), 27 patients (50% sensitivity and 88% specificity), and 48 patients (89% sensitivity and 82% specificity), respectively. Conclusions The use of the 2011 criteria will facilitate the diagnosis of LQTS and will decrease the number of false negative results.
  • Antiplatelet therapy discontinuation and the risk of serious cardiovascular events after coronary stenting: Observations from the CREDO-Kyoto registry cohort-2
    Hirotoshi Watanabe, Takeshi Morimoto, Masahiro Natsuaki, Yutaka Furukawa, Yoshihisa Nakagawa, Kazushige Kadota, Kyohei Yamaji, Kenji Ando, Satoshi Shizuta, Hiroki Shiomi, Tomohisa Tada, Junichi Tazaki, Yoshihiro Kato, Mamoru Hayano, Mitsuru Abe, Takashi Tamura, Manabu Shirotani, Shinji Miki, Mitsuo Matsuda, Mamoru Takahashi, Katsuhisa Ishii, Masaru Tanaka, Takeshi Aoyama, Osamu Doi, Ryuichi Hattori, Masayuki Kato, Satoru Suwa, Akinori Takizawa, Yoshiki Takatsu, Eiji Shinoda, Hiroshi Eizawa, Teruki Takeda, Jong Dae Lee, Moriaki Inoko, Hisao Ogawa, Shuichi Hamasaki, Minoru Horie, Ryuji Nohara, Hirofumi Kambara, Hisayoshi Fujiwara, Kazuaki Mitsudo, Masakiyo Nobuyoshi, Toru Kita, Adnan Kastrati, Takeshi Kimura
    PLoS ONE 10 2015年04月
    Copyright: © 2015 Watanabe et al. Relation of antiplatelet therapy (APT) discontinuation with the risk of serious cardiovascular events has not been fully addressed yet. This study is aimed to evaluate the risk of ischemic event after APT discontinuation based on long-term APT status of large cohort. In the CREDO-Kyoto Registry Cohort-2 enrolling 15939 consecutive patients undergoing first coronary revascularization, 10470 patients underwent percutaneous coronary intervention either with bare-metal stents (BMS) only (N=5392) or sirolimus-eluting stents (SES) only (N=5078). Proportions of patients taking dual-APT were 67.3% versus 33.4% at 1-year, and 48.7% versus 24.3% at 5-year in the SES and BMS strata, respectively. We evaluated daily APT status (dual-, single- and no-APT) and linked the adverse events to the APT status just 1-day before the events. No-APT as compared with dual- or single-APT was associated with significantly higher risk for stent thrombosis (ST) beyond 1-month after SES implantation (cumulative incidence rates beyond 1-month: 1.23 versus 0.15/0.29, P < 0.001/ P < 0.001), while higher risk of no-APT for ST was evident only until 6-month after BMS implantation (incidence rates between 1- and 6-month: 8.43 versus 0.71/1.20, P < 0.001/ P < 0.001, and cumulative incidence rates beyond 6-month: 0.31 versus 0.11/0.08, P=0.16/ P=0.08). No-APT as compared with dual- or single-APT was also associated with significantly higher risk for spontaneous myocardial infarction (MI) and stroke regardless of the types of stents implanted. Single-APT as compared with dual-APT was not associated with higher risk for serious adverse events, except for the marginally higher risk for ST in the SES stratum. In conclusion, discontinuation of both aspirin and thienopyridines was associated with increased risk for serious cardiovascular events including ST, spontaneous MI and stroke beyond 1-month after coronary stenting.
  • 循環器疾患の発症とモザイク
    長谷川 奏恵, 大野 聖子, 堀江 稔
    循環器内科 77(4) 391-395 2015年04月
  • 滋賀医科大学アジア疫学研究センターの取り組み : NCD克服のための疫学研究・教育拠点を目指して(特別寄稿)
    三浦 克之, 堀江 稔, 野崎 和彦, 久松 隆史, Abbott Robert D.
    滋賀医科大学看護学ジャーナル 13(1) 8-14 2015年03月
    滋賀医科大学では2013年10月に、新しい総合研究棟(疫学研究拠点)としてアジア疫学研究センターが新築、開所した。本センターは、本学のこれまでの生活習慣病疫学研究の実績を生かし、良好な研究環境による国際共同疫学研究の実施、大規模データベースの管理とバイオバンクによる生体試料保存を行うことを可能にするものである。また、これと時期を同じくして、文部科学省の平成25年度博士課程教育リーディングプログラムが採択され、アジア疫学研究センターを教育基盤とした博士課程教育リーディングプログラム「アジア非感染性疾患(NCD)超克プロジェクト」が開始された。本プログラムでは国内外の産学官の広い分野においてアジア太平洋州のトップリーダーとして活躍するNCD対策の専門家を育成する。
  • Effect of preinfarction angina pectoris on long-term survival in patients with ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention
    Tomohiko Taniguchi, Hiroki Shiomi, Toshiaki Toyota, Takeshi Morimoto, Masaharu Akao, Kenji Nakatsuma, Koh Ono, Takeru Makiyama, Satoshi Shizuta, Yutaka Furukawa, Yoshihisa Nakagawa, Kenji Ando, Kazushige Kadota, Minoru Horie, Takeshi Kimura
    American Journal of Cardiology 114 1179-1186 2014年10月
    ©2014 Elsevier Inc. All rights reserved. The influence of preinfarction angina pectoris (AP) on long-term clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI) remains controversial. In 5,429 patients with acute myocardial infarction (AMI) enrolled in the Coronary Revascularization Demonstrating Outcome Study in Kyoto AMI Registry, the present study population consisted of 3,476 patients with STEMI who underwent primary PCI within 24 hours of symptom onset and in whom the data on preinfarction AP were available. Preinfarction AP defined as AP occurring within 48 hours of hospital arrival was present in 675 patients (19.4%). Patients with preinfarction AP was younger and more often had anterior AMI and longer total ischemic time, whereas they less often had history of heart failure, atrial fibrillation, and shock presentation. The infarct size estimated by peak creatinine phosphokinase was significantly smaller in patients with than in patients without preinfarction AP (median [interquartile range] 2,141 [965 to 3,867] IU/L vs 2,462 [1,257 to 4,495] IU/L, p < 0.001). The cumulative 5-year incidence of death was signi ficantly lower in patients with preinfarction AP (12.4% vs 20.7%, p < 0.001) with median follow-up interval of 1,845 days. After adjusting for confounders, preinfarction AP was independently associated with a lower risk for death (hazard ratio 0.69, 95% confidence interval 0.54 to 0.86, p = 0.001). The lower risk for 5-year mortality in patients with preinfarction AP was consistently observed across subgroups stratified by total ischemic time, initial Thrombolysis In Myocardial Infarction flow grade, hemodynamic status, infarct location, and diabetes mellitus. In conclusion, preinfarction AP was independently associated with lower 5-year mortality in patients with STEMI who underwent primary PCI.
  • 左室内血栓が急性に出現した拡張型心筋症の一例
    八木 典章, 山路 正之, 伊藤 英樹, 山本 孝, 浅井 徹, 堀江 稔
    滋賀医科大学雑誌 27(1) 9-13 2014年03月
    A 49-year-old male was admitted to our hospital for therapy of congestive heart failure. He underwent echocardiography, which revealed severe systolic dysfunction of left ventricle as dilated cardiomyopathy, while we were unable to detect thrombus in left ventricle on admission. Coagulation values for D-dimer, congenital antithrombin III and protein C were within the normal range. He was treated with continuous infusion of carperitide and furosemide.Though he immediately started to receive both heparin sodium at a dose of 10,000 units/day and warfarin potassium at a dose of 2 mg/day to avoid thrombus after admission, activated partial thromboplastin (APTT) time and prothrombin time-International normalized ratio (PT-INR) failed to be sufficiently prolonged. A few floating thrombi about 2 centimeters in diameter appeared around the apex of the left ventricle when his left ventricle was assessed by echocardiography after only 3 days .Emergency cardiotomy was performed and all thrombi were successfully removed. This is particularly important because thrombi could fall onto the aortic valve, which could lead to sudden death .
  • A rare KCNE1 polymorphism, D85N, as a genetic modifier of long QT syndrome
    Kanae Hasegawa, Seiko Ohno, Hideki Itoh, Takeru Makiyama, Takeshi Aiba, Yasutaka Nakano, Wataru Shimizu, Hiroshi Matsuura, Naomasa Makita, Minoru Horie
    Journal of Arrhythmia 30 161-166 2014年01月
    © 2013 Japanese Heart Rhythm Society. Published by Elsevier B.V. All rights reserved. Background: The gene KCNE1 encodes the β-subunit of cardiac voltage-gated K + channels and causes long QT syndrome (LQTS). LQTS is characterized by the prolongation of QT interval and lethal arrhythmias such as torsade de pointes (TdP). A KCNE1 polymorphism, D85N, has been shown to modify the phenotype of LQTS through a loss-of-function effect on both KCNQ1 and KCNH2 channels when co-expressed and reconstituted in a heterologous expression system. Methods: A screening for the D85N polymorphism was performed in 355 LQTS families with mutations in KCNQ1, KCNH2, or SCN5A. Among the probands who had a heterozygous status with the polymorphism, we focused on a family with a KCNH2 mutation (E58K), a N-terminal missense mutation, and examined the clinical significance of this polymorphism. We also conducted biophysical assays to analyze the effect of the polymorphism in mammalian cells. Results: In 355 probands, we found 14 probands (3.9%) who had a heterozygous compound status with the D85N polymorphism. In the family with a KCNE1-D85N polymorphism and a KCNH2-E58K mutation, the proband and her daughter carried both the KCNH2 mutation and the KCNE1-D85N polymorphism. They experienced repetitive syncope and TdP. Two sons of the proband had either KCNH2-E58K mutation or KCNE1-D85N, but were asymptomatic. Biophysical assays of KCNE1-D85N with KCNH2-E58K variants produced a larger reduction in the reconstituted I Kr currents compared to co-expression with wild-type KCNE1. Conclusions: The KCNE1-D85N polymorphism modified the clinical features of LQTS patients.
  • Gain-of-function KCNH2 mutations in patients with Brugada syndrome
    Qi Wang, Seiko Ohno, Wei Guang Ding, Megumi Fukuyama, Akashi Miyamoto, Hideki Itoh, Takeru Makiyama, Jie Wu, Jiayu Bai, Kanae Hasegawa, Tetsuji Shinohara, Naohiko Takahashi, Akihiko Shimizu, Hiroshi Matsuura, Minoru Horie
    Journal of Cardiovascular Electrophysiology 25 522-530 2014年01月
    Novel KCNH2 Mutations in Brugada Syndrome Background Brugada syndrome (BrS) is an inherited disease characterized by right precordial ST segment elevation on electrocardiograms (ECGs) that predisposes patients to sudden cardiac death as a result of polymorphic ventricular tachyarrhythmia or ventricular fibrillation (VF). In BrS patients, except for SCN5A, mutations in other responsible genes are poorly elucidated. Methods and Results We identified 4 KCNH2 mutations, T152I, R164C, W927G, and R1135H, in 236 consecutive probands with BrS or Brugada-like ECG. Three of these mutation carriers showed QTc intervals shorter than 360 milliseconds and 1 experienced VF. We performed patch-clamp analyses on I Kr reconstituted with the KCNH2 mutations in Chinese hamster ovary cells and compared the phenotypes of the patients with different genotypes. Three mutations, R164C, W927G, and R1135H, increased I Kr densities. Three mutations, T152I, R164C, and W927G, caused a negative shift in voltage-dependent activation curves. Only the R1135H mutant channel prolonged the deactivation time constants. We also identified 20 SCN5A and 5 CACNA1C mutation carriers in our cohort. Comparison of probands' phenotypes with 3 different genotypes revealed that KCNH2 mutation carriers showed shorter QTc intervals and SCN5A mutation carriers had longer QRS durations. Conclusions All KCNH2 mutations that we identified in probands with BrS exerted gain-of-function effects on I Kr channels, which may partially explain the ECG findings in our patients. © 2014 Wiley Periodicals, Inc.
  • Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes
    Silvia G. Priori, Silvia G. Priori, Silvia G. Priori, Arthur A. Wilde, Arthur A. Wilde, Minoru Horie, Yongkeun Cho, Elijah R. Behr, Charles Berul, Nico Blom, Josep Brugada, Chern En Chiang, Heikki Huikuri, Prince Kannankeril, Andrew Krahn, Antoine Leenhardt, Arthur Moss, Peter J. Schwartz, Wataru Shimizu, Gordon Tomaselli, Cynthia Tracy
    Journal of Arrhythmia 30 29-47 2014年01月
  • A novel KCNQ1 missense mutation identified in a patient with juvenile-onset atrial fibrillation causes constitutively open IKs channels
    Kanae Hasegawa, Kanae Hasegawa, Seiko Ohno, Takashi Ashihara, Hideki Itoh, Wei Guang Ding, Futoshi Toyoda, Takeru Makiyama, Hisaaki Aoki, Yoshihide Nakamura, Brian P. Delisle, Hiroshi Matsuura, Minoru Horie
    Heart Rhythm 11 67-75 2014年01月
    Background Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. In some patients, the disease is inheritable; however, hereditary aspects of AF remain not fully elucidated. Objective The purpose of this study was to identify genetic backgrounds that contribute to juvenile-onset AF and to define the mechanism. Methods In 30 consecutive juvenile-onset AF patients (onset age < 50 years), we screened AF-related genes (KCNQ1, KCNH2, KCNE1-3, KCNE5, KCNJ2, SCN5A). We analyzed the function of mutant channels using whole-cell patch-clamp techniques and computer simulations. Results Among the juvenile-onset AF patients, we identified three mutations (10%): SCN5A-M1875T, KCNJ2-M301K, and KCNQ1-G229D. Because KCNQ1 variant (G229D) identified in a 16-year-old boy was novel, we focused on the proband. The G229D-I Ks was found to induce a large instantaneous activating component without deactivation after repolarization to-50 mV. In addition, wild-type (WT)/G229D-I Ks (WT and mutant coexpression) displayed both instantaneous and time-dependent activating currents. Compared to WT-I Ks , the tail current densities in WT/G229D-I Ks were larger at test potentials between-130 and-40 mV but smaller at test potentials between 20 and 50 mV. Moreover, WT/G229D-I Ks resulted in a negative voltage shift for current activation (-35.2 mV) and slower deactivation. WT/G229D-I Ks conducted a large outward current induced by an atrial action potential waveform, and computer simulation incorporating the WT/G229D-I Ks results revealed that the mutation shortened atrial but not ventricular action potential. Conclusion A novel KCNQ1-G229D mutation identified in a juvenile-onset AF patient altered the I Ks activity and kinetics, thereby increasing the arrhythmogenicity to AF. © 2014 Heart Rhythm Society. All rights reserved.
  • Late adverse events after implantation of sirolimus-eluting stent and bare-metal stent long-term (5-7 years) follow-up of the coronary revascularization demonstrating outcome study-kyoto registry cohort-2
    Masahiro Natsuaki, Takeshi Morimoto, Takeshi Morimoto, Yutaka Furukawa, Yutaka Furukawa, Yoshihisa Nakagawa, Yoshihisa Nakagawa, Kazushige Kadota, Kazushige Kadota, Kyohei Yamaji, Kyohei Yamaji, Kenji Ando, Kenji Ando, Satoshi Shizuta, Hiroki Shiomi, Tomohisa Tada, Junichi Tazaki, Yoshihiro Kato, Mamoru Hayano, Mitsuru Abe, Mitsuru Abe, Takashi Tamura, Takashi Tamura, Manabu Shirotani, Manabu Shirotani, Shinji Miki, Shinji Miki, Mitsuo Matsuda, Mitsuo Matsuda, Mamoru Takahashi, Mamoru Takahashi, Katsuhisa Ishii, Katsuhisa Ishii, Masaru Tanaka, Masaru Tanaka, Takeshi Aoyama, Takeshi Aoyama, Osamu Doi, Osamu Doi, Ryuichi Hattori, Ryuichi Hattori, Masayuki Kato, Masayuki Kato, Satoru Suwa, Satoru Suwa, Akinori Takizawa, Akinori Takizawa, Yoshiki Takatsu, Yoshiki Takatsu, Yoshiki Takatsu, Eiji Shinoda, Eiji Shinoda, Eiji Shinoda, Hiroshi Eizawa, Hiroshi Eizawa, Teruki Takeda, Teruki Takeda, Jong Dae Lee, Jong Dae Lee, Moriaki Inoko, Moriaki Inoko, Hisao Ogawa, Hisao Ogawa, Shuichi Hamasaki, Shuichi Hamasaki, Minoru Horie, Minoru Horie, Ryuji Nohara, Ryuji Nohara, Hirofumi Kambara, Hirofumi Kambara, Hisayoshi Fujiwara, Hisayoshi Fujiwara, Kazuaki Mitsudo, Kazuaki Mitsudo, Masakiyo Nobuyoshi, Masakiyo Nobuyoshi, Toru Kita, Toru Kita, Takeshi Kimura
    Circulation: Cardiovascular Interventions 7 168-179 2014年01月
    Background-Late adverse events such as very late stent thrombosis (VLST) or late target-lesion revascularization (TLR) after first-generation sirolimus-eluting stents (SES) implantation have not been yet fully characterized at long term in comparison with those after bare-metal stent (BMS) implantation. Methods and Results-Among 13 058 consecutive patients undergoing first percutaneous coronary intervention in the Coronary REvascularization Demonstrating Outcome study-Kyoto registry Cohort-2, 5078 patients were treated with SES only, and 5392 patients were treated with BMS only. During 7-year follow-up, VLST and late TLR beyond 1 year after SES implantation occurred constantly and without attenuation at 0.24% per year and at 2.0% per year, respectively. Cumulative 7-year incidence of VLST was significantly higher in the SES group than that in the BMS group (1.43% versus 0.68%, P < 0.0001). However, there was no excess of all-cause death beyond 1 year in the SES group as compared with that in the BMS group (20.8% versus 19.6%, P=0.91). Cumulative incidences of late TLR (both overall and clinically driven) were also significantly higher in the SES group than in the BMS group (12.0% versus 4.1%, P < 0.0001 and 8.5% versus 2.6%, P < 0.0001, respectively), leading to late catch-up of the SES group to the BMS group regarding TLR through the entire 7-year follow-up (18.8% versus 25.2%, and 10.6% versus 10.2%, respectively). Clinical presentation as acute coronary syndrome was more common at the time of late SES TLR compared with early SES TLR (21.2% and 10.0%). Conclusions-Late catch-up phenomenon regarding stent thrombosis and TLR was significantly more pronounced with SES than that with BMS. This limitation should remain the target for improvements of DES technology. © 2014 American Heart Association, Inc.
  • Nonsense-mediated mRNA decay due to a CACNA1C splicing mutation in a patient with Brugada syndrome
    Megumi Fukuyama, Seiko Ohno, Qi Wang, Takeshi Shirayama, Hideki Itoh, Minoru Horie
    Heart Rhythm 11 629-634 2014年01月
    Background: Brugada syndrome (BrS) is an inherited cardiac arrhythmia associated with sudden death due to ventricular fibrillation. Mutations in genes related to the cardiac L-type calcium channel have been reported to be causative of BrS. Generally, the messenger RNA (mRNA) that contains a nonsense mutation is rapidly degraded via its decay pathway, which is known as nonsense-mediated mRNA decay (NMD). Previously, we reported a male patient with BrS who carried c.1896G > A (the first nucleotide of CACNA1C exon 14), which caused a synonymous mutation, p.R632R. Objective: To examine how the synonymous CACNA1C mutation p.R632R produces the phenotype of BrS, with a special emphasis on the splicing error and NMD processes. Methods: We extracted mRNA from leukocytes of the proband and his 2 children and performed reverse transcription polymerase chain reaction. Complementary DNAs were checked by using direct sequencing and quantitative analysis. Results: The subsequent sequence electropherogram of the complementary DNAs did not show the substitution of the nucleotide identified in the genomic DNA of the proband. In the mRNA quantification analysis, we confirmed that reduction in the CACNA1C expression level was suspected to be caused by NMD. Conclusions: Mutant mRNA with a c.1896G > A substitution may be diminished by NMD, and the resultant decrease in CACNA1C message leads to a novel mechanism for inducing BrS that is distinct from that reported previously. © 2014 Heart Rhythm Society. All rights reserved.
  • Diagnosis and management of patients with inherited primary arrhythmia syndromes
    Minoru Horie
    Respiration and Circulation 62 832-840 2014年01月
  • Genetic characteristics of children and adolescents with long-QT syndrome diagnosed by school-based electrocardiographic screening programs
    Masao Yoshinaga, Yu Kucho, Jav Sarantuya, Yumiko Ninomiya, Hitoshi Horigome, Hiroya Ushinohama, Wataru Shimizu, Minoru Horie
    Circulation: Arrhythmia and Electrophysiology 7 107-112 2014年01月
    Background-A school-based electrocardiographic screening program has been developed in Japan. However, few data are available on the genetic characteristics of pediatric patients with long-QT syndrome who were diagnosed by this program. Methods and Results-A total of 117 unrelated probands aged =18 years were the subjects who were referred to our centers for genetic testing. Of these, 69 subjects diagnosed by the program formed the screened group. A total of 48 subjects were included in the clinical group and were diagnosed with long-QT syndrome-related symptoms, familial study, or by chance. Mutations were classified as radical, of high probability of pathogenicity, or of uncertain significance. Two subjects in the clinical group died. Genotypes were identified in 50 (72%) and 23 (48%) of subjects in the screened and clinical groups, respectively. Of the KCNQ1 or KCNH2 mutations, 31 of 33 (94%) in the screened group and 15 of 16 (94%) in the clinical group were radical and of high probability of pathogenicity. Prevalence of symptoms before (9/69 versus 31/48; P < 0.0001) and after (12/69 versus 17/48; P=0.03) diagnosis was significantly lower in the screened group when compared with that in the clinical group although the QTc values, family history of long-QT syndrome, sudden death, and follow-up periods were not different between the groups. Conclusions-These data suggest that the screening program may be effective for early diagnosis of long-QT syndrome that may allow intervention before symptoms. In addition, screened patients should have follow-up equivalent to clinically identified patients. © 2013 American Heart Association, Inc.
  • HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes
    Silvia G. Priori, Silvia G. Priori, Silvia G. Priori, Arthur A. Wilde, Arthur A. Wilde, Minoru Horie, Yongkeun Cho, Elijah R. Behr, Charles Berul, Nico Blom, Josep Brugada, Chern En Chiang, Heikki Huikuri, Prince Kannankeril, Andrew Krahn, Antoine Leenhardt, Arthur Moss, Peter J. Schwartz, Wataru Shimizu, Gordon Tomaselli, Cynthia Tracy
    Journal of Arrhythmia 30 1-28 2014年01月
  • Cardiac channelopathies associated with infantile fatal ventricular arrhythmias: From the cradle to the bench
    Koichi Kato, Takeru Makiyama, Jie Wu, Jie Wu, Wei Guang Ding, Hiromi Kimura, Nobu Naiki, Seiko Ohno, Hideki Itoh, Toshio Nakanishi, Hiroshi Matsuura, Minoru Horie
    Journal of Cardiovascular Electrophysiology 25 66-73 2014年01月
    Channelopathies in Infantile Arrhythmias Background Fatal ventricular arrhythmias in the early period of life have been associated with cardiac channelopathies for decades, and postmortem analyses in SIDS victims have provided evidence of this association. However, the prevalence and functional properties of cardiac ion channel mutations in infantile fatal arrhythmia cases are not clear. Methods and Results Seven infants with potentially lethal arrhythmias at age < 1 year (5 males, age of onset 44.1 ± 72.1 days) were genetically analyzed for KCNQ1, KCNH2, KCNE1-5, KCNJ2, SCN5A, GJA5, and CALM1 by using denaturing high-performance liquid chromatography and direct sequencing. Whole-cell currents of wildtype and mutant channels were recorded and analyzed in Chinese hamster ovary cells transfected with SCN5A and KCNH2 cDNA. In 5 of 7 patients, we identified 4 mutations (p.N1774D, p.T290fsX53, p.F1486del and p.N406K) in SCN5A, and 1 mutation (p.G628D) in KCNH2. N1774D, F1486del, and N406K in SCN5A displayed tetrodotoxin-sensitive persistent late Na + currents. By contrast, SCN5A-T290fsX53 was nonfunctional. KCNH2-G628D exhibited loss of channel function. Conclusion Genetic screening of 7 patients was used to demonstrate the high prevalence of cardiac channelopathies. Functional assays revealed both gain and loss of channel function in SCN5A mutations, as well as loss of function associated with the KCNH2 mutation. © 2014 Wiley Periodicals, Inc.
  • Successful control of life-threatening polymorphic ventricular tachycardia by radiofrequency catheter ablation in an infant
    Yuriko Abe, Naokata Sumitomo, Hiromi Okuma, Takahiro Nakamura, Junji Fukuhara, Rie Ichikawa, Masaharu Matsumura, Michio Miyashita, Hiroshi Kamiyama, Mamoru Ayusawa, Mamie Watanabe, Kunitaka Joo, Naomasa Makita, Minoru Horie
    Heart and Vessels 29 422-426 2014年01月
    We present a case of a 9-month-old girl in whom malignant polymorphic ventricular tachycardia (VT) was successfully controlled by radiofrequency catheter ablation under guidance with a three-dimensional mapping system. The VTs originated from the left ventricular lateral wall, left ventricular anterior wall, and left ventricular apex. At least six types of VTs were documented during the electrophysiology study. All VTs were successfully controlled after two sessions of radiofrequency catheter ablation, and she was discharged from our hospital on propranolol, mexiletine, flecainide, and aprindine. © Springer 2013.
  • Exon 3 deletion of RYR2 encoding cardiac ryanodine receptor is associated with left ventricular non-compaction
    Seiko Ohno, Masato Omura, Mihoko Kawamura, Hiromi Kimura, Hideki Itoh, Takeru Makiyama, Hiroya Ushinohama, Naomasa Makita, Minoru Horie
    Europace 16 1646-1654 2014年01月
    © 2014 Published on behalf of the European Society of Cardiology. All rights reserved. Methods and results Our cohort consisted of 24 CPVT probands. Polymerase chain reaction (PCR)-based conventional genetic analysis did not identify any mutations in coding exons of RYR2 in these probands. They were screened using multiplex ligation-dependent probe amplification (MLPA). In probands identified with RYR2 exon 3 deletion, the precise location of the deletion was identified by quantitative PCR and direct sequencing methods. We identified two CPVT probands from unrelated families who harboured a large deletion including exon 3. The probands were 9- and 17-year-old girls. Both probands had a history of syncope related to emotional stress or exercise, exhibited bradycardia, and were diagnosed with left ventricular non-compaction (LVNC). We examined 10 family members and identified six more RYR2 exon 3 deletion carriers. In total, there were eight carriers, of which seven were diagnosed with LVNC (87.5%). Two carriers under the age of 4 years remained asymptomatic, although they were diagnosed with LVNC. Using quantitative PCR and direct sequencing, we confirmed that the deletions were 1.1 and 37.7 kb in length. Conclusion RYR2 exon 3 deletion is frequently associated with LVNC. Therefore, detection of the deletion offers a new modality for predicting the prognosis of patients with LVNC with ventricular/atrial arrhythmias, particularly in children. Aims Ryanodine receptor gene (RYR2) mutations are well known to cause catecholaminergic polymorphic ventricular tachycardia (CPVT). Recently, RYR2 exon 3 deletion has been identified in patients with dilated cardiomyopathy (DCM) and/or CPVT. This study aimed to screen for the RYR2 exon 3 deletion in CPVT probands, characterize its clinical pathology, and confirm the genomic rearrangement.
  • Clinical usefulness of a novel program “Heart Function View” for evaluating cardiac function from gated myocardial perfusion SPECT
    Ichiro Nakae, Hideki Hayashi, Tetsuya Matsumoto, Kenichi Mitsunami, Minoru Horie
    Annals of Nuclear Medicine 28 812-823 2014年01月
    © 2014, The Japanese Society of Nuclear Medicine. Objective: To investigate clinical usefulness of a novel program “Heart Function View (HFV)” for evaluating left ventricular (LV) function from myocardial perfusion SPECT (MPS), we compared LV functional parameters (F(x)) calculated by HFV with those obtained by the other similar programs QGS and cardioGRAF or by ultrasound echocardiography (UCG) and examined their correlations with clinical markers of heart failure: plasma BNP concentrations (BNPs) and exercise capacity. Methods: Studied patients (n = 60) underwent technetium-99m tetrofosmin quantitative gated MPS including treadmill exercise for examining heart disease. Myocardial stress images were acquired 30 min after the first tracer injection during maximal exercise. Three hours later, the second tracer was injected, and resting images were acquired. LV systolic F(x) [ejection fraction (EF), peak ejection rate (PER)] and diastolic F(x) [first third filling fraction (1/3FF), first third filling rate (1/3FR), peak filling rate (PFR), time to PFR (TPF)] were analyzed, and phase standard deviation (SD) and histogram bandwidth were obtained by phase analysis. Results: LV end-diastolic volume (EDV), end-systolic volume (ESV) and EF obtained from HFV were well correlated with those from QGS, cardioGRAF and UCG. A diastolic parameter Doppler E/e′ from UCG was significantly with PFR from HFV. There were good correlations between LVEDV, LVESV, LVEF, PER, PFR, 1/3FR, TPF and 1/3FF from HFV and those from cardioGRAF. LVEF, PER, 1/3FR, and PFR were significantly correlated with plasma BNP concentrations. In patients with non-ischemic heart disease (n = 42), phase SD and histogram bandwidth were correlated negatively with exercise capacity or PFR. Conclusions: HFV-derived LVF(x) are correlated with LVF(x) from the other programs or UCG, or with the clinical markers of heart failure and are thus useful in the functional assessment for patients with heart disease.
  • Executive Summary: HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes
    Silvia G. Priori, Arthur A. Wilde, Minoru Horie, Yongkeun Cho, Elijah R. Behr, Charles Berul, Nico Blom, Josep Brugada, Chern En Chiang, Heikki Huikuri, Prince Kannankeril, Andrew Krahn, Antoine Leenhardt, Arthur Moss, Peter J. Schwartz, Wataru Shimizu, Gordon Tomaselli, Cynthia Tracy
    Heart Rhythm 10 2013年12月
  • Effect of flecainide on T-wave alternans in andersen-tawil syndrome
    Hideki Hayashi, Tamiro Kawaguchi, Minoru Horie
    Annals of Noninvasive Electrocardiology 19 383-386 2014年01月
  • HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes: Document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013.
    Silvia G. Priori, Arthur A. Wilde, Minoru Horie, Yongkeun Cho, Elijah R. Behr, Charles Berul, Nico Blom, Josep Brugada, Chern En Chiang, Heikki Huikuri, Prince Kannankeril, Andrew Krahn, Antoine Leenhardt, Arthur Moss, Peter J. Schwartz, Wataru Shimizu, Gordon Tomaselli, Cynthia Tracy, Cynthia Tracy
    Heart Rhythm 10 1932-1963 2013年12月
  • Pharmacological correction of long QT-linked mutations in KCNH2 (hERG) increases the trafficking of Kv11.1 channels stored in the transitional endoplasmic reticulum
    Jennifer L. Smith, Allison R. Reloj, Parvathi S. Nataraj, Daniel C. Bartos, Elizabeth A. Schroder, Arthur J. Moss, Seiko Ohno, Minoru Horie, Corey L. Anderson, Craig T. January, Brian P. Delisle
    American Journal of Physiology - Cell Physiology 305 2013年11月
    KCNH2 encodes Kv11.1 and underlies the rapidly activating delayed rectifier K + current (I Kr ) in the heart. Loss-of-function KCNH2 mutations cause the type 2 long QT syndrome (LQT2), and most LQT2-linked missense mutations inhibit the trafficking of Kv11.1 channels. Drugs that bind to Kv11.1 and block I Kr (e.g., E-4031) can act as pharmacological chaperones to increase the trafficking and functional expression for most LQT2 channels (pharmacological correction). We previously showed that LQT2 channels are selectively stored in a microtubuledependent compartment within the endoplasmic reticulum (ER). We tested the hypothesis that pharmacological correction promotes the trafficking of LQT2 channels stored in this compartment. Confocal analyses of cells expressing the trafficking-deficient LQT2 channel G601S showed that the microtubule-dependent ER compartment is the transitional ER. Experiments with E-4031 and the protein synthesis inhibitor cycloheximide suggested that pharmacological correction promotes the trafficking of G601S stored in this compartment. Treating cells in E-4031 or ranolazine (a drug that blocks I Kr and has a short half-life) for 30 min was sufficient to cause pharmacological correction. Moreover, the increased functional expression of G601S persisted 4-5 h after drug washout. Coexpression studies with a dominant- negative form of Rab11B, a small GTPase that regulates Kv11.1 trafficking, prevented the pharmacological correction of G601S trafficking from the transitional ER. These data suggest that pharmacological correction quickly increases the trafficking of LQT2 channels stored in the transitional ER via a Rab11B-dependent pathway, and we conclude that the pharmacological chaperone activity of drugs like ranolazine might have therapeutic potential. © 2013 the American Physiological Society.
  • Sudden cardiac arrest recorded during Holter monitoring: Prevalence, antecedent electrical events, and outcomes
    Eiichi Watanabe, Teruhisa Tanabe, Motohisa Osaka, Akiko Chishaki, Bonpei Takase, Shinichi Niwano, Ichiro Watanabe, Kaoru Sugi, Takao Katoh, Kan Takayanagi, Koushi Mawatari, Minoru Horie, Ken Okumura, Hiroshi Inoue, Hirotsugu Atarashi, Iwao Yamaguchi, Susumu Nagasawa, Kazuo Moroe, Itsuo Kodama, Tsuneaki Sugimoto, Yoshifusa Aizawa
    Heart Rhythm 11 1418-1425 2014年01月
    Background Causative arrhythmias of sudden cardiac arrest (SCA) are changing in this age of improved coronary care. Objective The purpose of this study was to examine the frequency of terminal arrhythmias and the electrical events prior to SCA. Methods We analyzed 24-hour Holter recordings of 132 patients enrolled from 41 institutions who either died (n = 88) or had an aborted death (n = 44). The Holter recordings were obtained for diagnosing and evaluating diseases and arrhythmias in those without any episodes suggestive of SCA. Results In 97 patients (73%), SCA was associated with ventricular tachyarrhythmias and in 35 (27%) with bradyarrhythmias. The bradyarrhythmia- related SCA patients were older than those with a tachyarrhythmia-related SCA (70 ± 13 years vs 58 ± 19 years, P < .001). The most common arrhythmia for a tachyarrhythmia-related SCA was ventricular tachycardia degenerating to ventricular fibrillation (45%). The bradyarrhythmia-related SCA was caused by asystole (74%) or AV block (26%). Spontaneous conversion was observed in 37 patients (38%) with ventricular tachyarrhythmias. Of those, 62% of the patients experienced symptoms including syncope, chest pain, or convulsion. Multivariate logistic analysis revealed that independent predictors of mortality for tachyarrhythmia-related SCAs were advanced age (odds ratio 1.04, 95% confidence interval 1.02-1.08) and ST elevation within the hour before SCA (odds ratio 3.54, 95% confidence interval 1.07-13.5). In contrast, the presence of preceding torsades de pointes was associated with spontaneous conversion (odds ratio 0.20, 95% confidence interval 0.05-0.66). Conclusion The most frequent cause of SCA remains ventricular tachyarrhythmias. Advanced age and ST elevation before SCA are risk factors for mortality in tachyarrhythmia-related SCAs. © 2014 Heart Rhythm Society. All right sreserved.
  • Erratum: Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death (Nature Genetics (2013) 45 (1044-1049))
    Connie R. Bezzina, Julien Barc, Yuka Mizusawa, Carol Ann Remme, Jean Baptiste Gourraud, Floriane Simonet, Arie O. Verkerk, Peter J. Schwartz, Lia Crotti, Federica Dagradi, Pascale Guicheney, Véronique Fressart, Antoine Leenhardt, Charles Antzelevitch, Susan Bartkowiak, Eric Schulze-Bahr, Sven Zumhagen, Elijah R. Behr, Rachel Bastiaenen, Jacob Tfelt-Hansen, Morten Salling Olesen, Stefan Kääb, Britt M. Beckmann, Peter Weeke, Hiroshi Watanabe, Naoto Endo, Tohru Minamino, Minoru Horie, Seiko Ohno, Kanae Hasegawa, Naomasa Makita, Akihiko Nogami, Wataru Shimizu, Takeshi Aiba, Philippe Froguel, Beverley Balkau, Olivier Lantieri, Margherita Torchio, Cornelia Wiese, David Weber, Rianne Wolswinkel, Ruben Coronel, Bas J. Boukens, Stéphane Bézieau, Eric Charpentier, Stéphanie Chatel, Aurore Despres, Françoise Gros, Florence Kyndt, Simon Lecointe, Pierre Lindenbaum, Vincent Portero, Jade Violleau, Manfred Gessler, Hanno L. Tan, Dan M. Roden, Vincent M. Christoffels, Hervé Le Marec, Arthur A. Wilde, Vincent Probst, Jean Jacques Schott, Christian Dina, Richard Redon
    Nature Genetics 45 1409 2013年11月
  • Clinical significance of lung iodine-123 metaiodobenzylguanidine uptake assessment in Parkinson's and heart diseases
    Ichiro Nakae, Hideki Hayashi, Kenichi Mitsunami, Minoru Horie
    Annals of Nuclear Medicine 27 737-747 2013年10月
    Objective: Decreased heart iodine-123 metaiodobenzylguanidine ( 123 I-MIBG) uptake [heart-to-mediastinum count ratio (H/M)] is reported in heart disease (HD) or Lewy body disease (LBD). When LBD is merged, therefore, information regarding HD severity may be ambiguous. We aimed to examine whether lung 123 I-MIBG uptake [lung-to-mediastinum count ratio (L/M)] assessment might be useful for differentiating two clinical conditions of HD and LBD, and to investigate whether L/M could reflect the grade of left ventricular (LV) dysfunction. Methods: Three groups were examined: LBD (patient group with Parkinson's disease or dementia with Lewy bodies, n = 33), PS (group with other Parkinsonian syndromes, n = 20) and HD (group with heart disease). HD consisted of 4 subgroups: HD(I) [H/M( < 2.30)-matched group with LBD, n = 34), HD(II) [H/M(≥2.30)-matched group with PS, n = 33], HD(III) [group for functional analysis, LV ejection fraction, first-third and peak filling rates (1/3FR and PFR) and time to PFR were calculated using gated SPECT, n = 35] and HD(IV) (group for examining cardiac prognosis, follow-up period of 1283 ± 506 days, n = 54). Using Doppler echocardiography, a diastolic parameter E/e′ and pulmonary artery pressure (ePAP) were estimated. Results: H/Ms did not differ between HD(I) and LBD, or between PS and HD(II). However, L/Ms were increased in the order of LBD, PS, HD(II) and HD(I) groups. In combined LBD, PS, HD(I) and HD(II), L/Ms correlated positively with a diastolic parameter E/e′. L/Ms correlated with ePAP, while H/Ms did not. H/Ms correlated with a systolic parameter EF (r = 0.56) and diastolic parameters 1/3FR (r = 0.51) and PFR (r = 0.51), and L/Ms correlated with diastolic parameters 1/3FR (r = -0.36) and PFR (r = -0.36) but not with EF in HD(III). Kaplan-Meier analysis showed earlier cardiac death in patients with decreased H/Ms, but not in patients with increased L/Ms in HD(IV). Conclusions: Our study suggest that increased lung 123 I-MIBG uptake is useful as a reference marker for differentiating two clinical conditions of HD and LBD, and can reflect the degree of LV diastolic dysfunction. Elevated ePAP caused by LV diastolic dysfunction may be involved in the mechanism(s) of increased lung uptake. © 2013 The Japanese Society of Nuclear Medicine.
  • Executive summary: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes.
    Silvia G. Priori, Arthur A. Wilde, Minoru Horie, Yongkeun Cho, Elijah R. Behr, Charles Berul, Nico Blom, Josep Brugada, Chern En Chiang, Heikki Huikuri, Prince Kannankeril, Andrew Krahn, Antoine Leenhardt, Arthur Moss, Peter J. Schwartz, Wataru Shimizu, Gordon Tomaselli, Cynthia Tracy, Document Reviewers, Michael Ackerman, Bernard Belhassen, N. A.Mark Estes, Diane Fatkin, Jonathan Kalman, Elizabeth Kaufman, Paulus Kirchhof, Eric Schulze-Bahr, Christian Wolpert, Jitendra Vohra, Marwan Refaat, Susan P. Etheridge, Robert M. Campbell, Edward T. Martin, Swee Chye Quek, Heart Rhythm Society, European Heart Rhythm Association, Asia Pacific Heart Rhythm Society
    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 15 1389-1406 2013年10月
  • Electrical storm in idiopathic ventricular fibrillation is associated with early repolarization
    Yoshifusa Aizawa, Yoshifusa Aizawa, Masaomi Chinushi, Kanae Hasegawa, Nobu Naiki, Minoru Horie, Yoshiaki Kaneko, Masahiko Kurabayashi, Shogo Ito, Tsutomu Imaizumi, Yoshiyasu Aizawa, Seiji Takatsuki, Kunitake Joo, Masahito Sato, Katsuya Ebe, Yukio Hosaka, Michel Haissaguerre, Keiichi Fukuda
    Journal of the American College of Cardiology 62 1015-1019 2013年09月
    Objectives This study sought to characterize patients with idiopathic ventricular fibrillation (IVF) who develop electrical storms. Background Some IVF patients develop ventricular fibrillation (VF) storms, but the characteristics of these patients are poorly known. Methods Ninety-one IVF patients (86% male) were selected after the exclusion of structural heart diseases, primary electrical diseases, and coronary spasm. Electrocardiogram features were compared between the patients with and without electrical storms. A VF storm was defined as VF occurring ≥3 times in 24 h and J waves > 0.1 mV above the isoelectric line in contiguous leads. Results Fourteen (15.4%) patients had VF storms occurring out-of-hospital at night or in the early morning. J waves were more closely associated with VF storms compared to patients without VF storms: 92.9% versus 36.4% (p < 0.0001). VF storms were controlled by intravenous isoproterenol, which attenuated the J-wave amplitude. After the subsidence of VF storms, the J waves decreased to the nondiagnostic level during the entire follow-up period. Implantable cardioverter-defibrillator therapy was administered to all patients during follow-up. Quinidine therapy was limited, but the patients on disopyramide (n = 3), bepridil (n = 1), or isoprenaline (n = 1) were free from VF recurrence, while VF recurred in 5 of the 9 patients who were not given antiarrhythmic drugs. Conclusions The VF storms in the IVF patients were highly associated with J waves that showed augmentation prior to the VF onset. Isoproterenol was effective in controlling VF and attenuated the J waves, which diminished to below the diagnostic level during follow-up. VF recurred in patients followed up without antiarrhythmic agents. © 2013 by the American College of Cardiology Foundation Published by Elsevier Inc.
  • Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death
    Connie R. Bezzina, Julien Barc, Julien Barc, Yuka Mizusawa, Carol Ann Remme, Jean Baptiste Gourraud, Jean Baptiste Gourraud, Jean Baptiste Gourraud, Jean Baptiste Gourraud, Floriane Simonet, Floriane Simonet, Floriane Simonet, Arie O. Verkerk, Peter J. Schwartz, Peter J. Schwartz, Peter J. Schwartz, Peter J. Schwartz, Peter J. Schwartz, Peter J. Schwartz, Lia Crotti, Lia Crotti, Lia Crotti, Federica Dagradi, Federica Dagradi, Pascale Guicheney, Pascale Guicheney, Véronique Fressart, Véronique Fressart, Véronique Fressart, Antoine Leenhardt, Antoine Leenhardt, Antoine Leenhardt, Charles Antzelevitch, Susan Bartkowiak, Eric Schulze-Bahr, Sven Zumhagen, Elijah R. Behr, Rachel Bastiaenen, Jacob Tfelt-Hansen, Jacob Tfelt-Hansen, Morten Salling Olesen, Morten Salling Olesen, Stefan Kääb, Stefan Kääb, Britt M. Beckmann, Peter Weeke, Hiroshi Watanabe, Naoto Endo, Tohru Minamino, Minoru Horie, Seiko Ohno, Kanae Hasegawa, Naomasa Makita, Akihiko Nogami, Wataru Shimizu, Wataru Shimizu, Takeshi Aiba, Philippe Froguel, Philippe Froguel, Philippe Froguel, Beverley Balkau, Beverley Balkau, Olivier Lantieri, Margherita Torchio, Margherita Torchio, Cornelia Wiese, David Weber, Rianne Wolswinkel, Ruben Coronel, Bas J. Boukens, Bas J. Boukens, Stéphane Bézieau, Eric Charpentier, Eric Charpentier, Eric Charpentier, Stéphanie Chatel, Stéphanie Chatel, Stéphanie Chatel, Aurore Despres, Aurore Despres, Aurore Despres, Françoise Gros, Françoise Gros, Françoise Gros, Florence Kyndt, Florence Kyndt, Florence Kyndt, Florence Kyndt, Florence Kyndt, Simon Lecointe, Simon Lecointe, Simon Lecointe, Simon Lecointe, Pierre Lindenbaum, Pierre Lindenbaum, Pierre Lindenbaum, Pierre Lindenbaum, Vincent Portero, Vincent Portero, Vincent Portero
    Nature Genetics 45 1044-1049 2013年09月
    Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) and near the HEY2 gene (rs9388451). Independent replication confirmed both signals (meta-analyses: rs10428132, P = 1.0 × 10 -68; rs9388451, P = 5.1 × 10 -17) and identified one additional signal in SCN5A (at 3p21; rs11708996, P = 1.0 × 10 -14). The cumulative effect of the three loci on disease susceptibility was unexpectedly large (P trend = 6.1 × 10 -81). The association signals at SCN5A-SCN10A demonstrate that genetic polymorphisms modulating cardiac conduction can also influence susceptibility to cardiac arrhythmia. The implication of association with HEY2, supported by new evidence that Hey2 regulates cardiac electrical activity, shows that Brugada syndrome may originate from altered transcriptional programming during cardiac development. Altogether, our findings indicate that common genetic variation can have a strong impact on the predisposition to rare diseases. © 2013 Nature America, Inc. All rights reserved.
  • A novel SCN5A mutation demonstrating a variety of clinical phenotypes in familial sick sinus syndrome
    Seiko Nakajima, Takeru Makiyama, Koji Hanazawa, Kazuaki Kaitani, Masashi Amano, Yukiko Hayama, Naoaki Onishi, Yodo Tamaki, Makoto Miyake, Toshihiro Tamura, Hirokazu Kondo, Makoto Motooka, Chisato Izumi, Yoshihisa Nakagawa, Minoru Horie
    Internal Medicine 52 1805-1808 2013年08月
    Mutations in SCN5A have been reported to cause several types of hereditary arrhythmias (overlap syndrome). We herein report two patients with the overlapping phenotypes of juvenile sick sinus syndrome (SSS) and Brugada syndrome (BrS). The proband was a man who was in his twenties and had been diagnosed with both SSS and ventricular tachycardia (VT). A pilsicainide challenge test revealed a coved type ST segment elevation. His teenage brother also suffered from SSS, but no VT had been documented. A pilsicainide challenge failed to produce a Brugada-type ST elevation, but there was a marked prolo ngation of the His-ventricle interval. Their electrocardiograms at rest did not display any Brugada-type ST elevations. We identified a novel SCN5A (F1775Lfs*15) mutation in both patients, even though there was a phenotype discrepancy. © 2013 The Japanese Society of Internal Medicine.
  • Identification of a KCNQ1 polymorphism acting as a protective modifier against arrhythmic risk in long-QT syndrome
    Sabine Duchatelet, Lia Crotti, Lia Crotti, Lia Crotti, Rachel A. Peat, Rachel A. Peat, Isabelle Denjoy, Isabelle Denjoy, Hideki Itoh, Myriam Berthet, Myriam Berthet, Seiko Ohno, Véronique Fressart, Maria Cristina Monti, Cristina Crocamo, Matteo Pedrazzini, Federica Dagradi, Federica Dagradi, Alessandro Vicentini, Didier Klug, Paul A. Brink, Althea Goosen, Heikki Swan, Lauri Toivonen, Annukka M. Lahtinen, Kimmo Kontula, Kimmo Kontula, Wataru Shimizu, Minoru Horie, Alfred L. George, David Alexandre Trégouët, David Alexandre Trégouët, Pascale Guicheney, Pascale Guicheney, Peter J. Schwartz, Peter J. Schwartz, Peter J. Schwartz, Peter J. Schwartz
    Circulation: Cardiovascular Genetics 6 354-361 2013年08月
    Background-Long-QT syndrome (LQTS) is characterized by such striking clinical heterogeneity that, even among family members carrying the same mutation, clinical outcome can range between sudden death and no symptoms. We investigated the role of genetic variants as modifiers of risk for cardiac events in patients with LQTS. Methods and Results-In a matched case-control study including 112 patient duos with LQTS from France, Italy, and Japan, 25 polymorphisms were genotyped based on either their association with QTc duration in healthy populations or on their role in adrenergic responses. The duos were composed of 2 relatives harboring the same heterozygous KCNQ1 or KCNH2 mutation: 1 with cardiac events and 1 asymptomatic and untreated. The findings were then validated in 2 independent founder populations totaling 174 symptomatic and 162 asymptomatic patients with LQTS, and a metaanalysis was performed. The KCNQ1 rs2074238 T-allele was significantly associated with a decreased risk of symptoms 0.34 (0.19-0.61; P < 0.0002) and with shorter QTc (P < 0.0001) in the combined discovery and replication cohorts. Conclusions-We provide evidence that the KCNQ1 rs2074238 polymorphism is an independent risk modifier with the minor T-allele conferring protection against cardiac events in patients with LQTS. This finding is a step toward a novel approach for risk stratification in patients with LQTS. © 2013 American Heart Association, Inc.
  • Spontaneous coronary artery spasm accidentally detected by 320-row multi-detector computed tomography
    Tamiro Kawaguchi, Hideki Hayashi, Nobu Naiki, Hiroshi Sakai, Takashi Yamamoto, Masatoshi Fujita, Minoru Horie
    Journal of Cardiology Cases 8 2013年08月
    A 64-year-old woman was introduced to our hospital suspected of having angina pectoris. A 12-lead electrocardiogram showed negative T wave in inferior leads. An echocardiography revealed no abnormality. In 320-row multi-detector computed tomography (MDCT), a severe narrowing of the right coronary artery was detected with collateral vessels between the distal portion of the obstructed right coronary artery and the left anterior descending artery. Coronary angiography showed no stenosis of the right coronary artery and non-obstructive plaques in the left coronary artery. To provoke coronary artery spasm, acetylcholine was infused into the left coronary artery. But, no narrowing was inducible in the left coronary artery. After that, a spasm of the right coronary artery was observed without the injection of acetylcholine into the right coronary artery. The spasm was located in the same site as the narrowing on MDCT imaging. A calcium channel antagonist (benidipine hydrochloride 8. mg/day) and a nitrate (isosorbide dinitrate 80. mg) were effective for coronary artery spasm. < . Learning objective: Multi-detector computed tomography (MDCT) imaging is useful for examining coronary artery disease. In addition to evaluating coronary organic stenosis, 320-row MDCT could detect spontaneous coronary artery spasm. Although coronary artery spasm has to be taken into account, intracoronary injection of acetylcholine is necessary to diagnose coronary artery spasm. > . © 2013 Japanese College of Cardiology.
  • Pitfall of the meta-analysis regarding early repolarization pattern
    Hideki Hayashi, Yoshitaka Murakami, Minoru Horie
    Journal of the American College of Cardiology 62 86 2013年07月
  • 家族性心房細動 (特集 最新の心房細動の診療) -- (各種病態における心房細動の治療と管理)
    堀江 稔
    臨牀と研究 90(9) 1210-1214 2013年09月
  • Genetic background of catecholaminergic polymorphic ventricular tachycardia in Japan
    Mihoko Kawamura, Seiko Ohno, Nobu Naiki, Iori Nagaoka, Kenichi Dochi, Qi Wang, Kanae Hasegawa, Hiromi Kimura, Akashi Miyamoto, Yuka Mizusawa, Hideki Itoh, Takeru Makiyama, Naokata Sumitomo, Hiroya Ushinohama, Kotaro Oyama, Nobuyuki Murakoshi, Kazutaka Aonuma, Hitoshi Horigome, Takafumi Honda, Masao Yoshinaga, Makoto Ito, Minoru Horie
    Circulation Journal 77 1705-1713 2013年07月
    Background: The genetic background of catecholaminergic polymorphic ventricular tachycardia (CPVT) has been extensively investigated for the last decade in Western countries, but it remains unstudied in the Asian population. Methods and Results: In 50 Japanese probands from unrelated families who satisfied clinical criteria for CPVT, genetic testing was conducted in all exons on 3 CPVT-related genes: cardiac ryanodine receptor 2 (RYR2), calsequestrin 2 (CASQ2) and inward rectifier potassium channel 2 (KCNJ2), and the clinical features between RYR2-genotyped and -non-genotyped patient groups were compared. Genetic and clinical evaluation was also done in 46 family members. In the genetic screening, 28 (18 novel) RYR2 (56.0%), 1 compound heterozygous CASQ2 (2.0%) and 1 KCNJ2 (2.0%) mutation carriers were identified. In the RYR2 mutation-positive group, the frequency of bidirectional ventricular tachycardia and the use of β-blockers were significantly higher than in the mutation-negative group. In contrast, there was no significant difference in supraventricular arrhythmias between the 2 groups. With regard to disease penetrance, the number of family members of RYR2-genotyped probands with a clinical diagnosis of CPVT was high. Conclusions: Thirty gene mutation carriers were found for 3 genes in 50 probands clinically diagnosed as having CPVT. The penetrance of CPVT phenotype was significantly higher in RYR2 mutation carriers, thus RYR2 gene screening in CPVT patients would be indispensable to prevent unexpected cardiac sudden death of young family members.
  • 座談会 致死性不整脈診療の現状と今後の展望 (特集 致死性不整脈診療の最前線)
    堀江 稔, 田中 敏博, 渡部 裕
    最新医学 68(7) 1509-1519 2013年07月
  • 嚢胞性線維症 (第1土曜特集 イオンチャネル病のすべて)
    堀江 稔
    医学のあゆみ 245(9) 727-731 2013年06月
  • 不整脈源性右室心筋症
    堀江 稔
    循環器内科 73(4) 437-442 2013年04月
  • QT延長症候群 (特集 救急医療に必要な不整脈診療の実際) -- (知っておくと役立つ不整脈の知識)
    堀江 稔
    救急医学 = The Japanese journal of acute medicine 37(2) 218-223 2013年02月
  • 器質的心疾患を認めない不整脈の学校生活管理指導ガイドライン(2013年改訂版)
    吉永 正夫, 泉田 直己, 岩本 眞理, 牛ノ濱 大也, 住友 直方, 田内 宣生, 高橋 良明, 富田 英, 長嶋 正實, 堀米 仁志, 山内 邦昭, 阿部 勝已, 新垣 義夫, 上野 倫彦, 太田 邦雄, 佐藤 誠一, 高木 純一, 立野 滋, 檜垣 高史, 市田 蕗子, 白石 裕比湖, 杉 薫, 堀江 稔
    日本小児循環器学会雑誌 29(6) 277-290 2013年
  • スプライシング異常と循環器疾患
    脇坂 啓子, 堀江 稔
    循環器内科 70(5) 523-529 2011年11月
  • 3.日本におけるブルガダ症候群:診断と治療
    堀江 稔
    日本内科学会雑誌 100(0) 91b-92a 2011年
  • 致死性不整脈と遺伝子異常
    堀江 稔
    心臓 43(10) 1291-1296 2011年
  • 低酸素脳症が残存したカテコラミン誘発性心室頻拍の1例
    脇屋 桃子, 久次米 真吾, 伊藤 尚志, 榎本 善成, 森山 明義, 沼田 綾香, 熊谷 賢太, 酒井 毅, 坂田 隆夫, 野呂 眞人, 杉 薫, 堀江 稔
    心臓 43(2) S2_81-S2_85 2011年
    症例: 14歳, 男性.
    経過: 12歳ごろより運動後に前失神症状を自覚していた. 運動後に心肺停止となり緊急搬送となった. 来院時は心室細動で, 循環動態は破綻していた. 直流通電施行後も, 持続性心室頻拍が頻回に出現した. 人工呼吸器管理下で体外補助循環, 低体温療法を施行したが, 低酸素脳症が残存した. 洞調律復帰後の心電図に経時的な異常は認めなかった. 心臓電気生理学的検査では, 無投薬下では病的不整脈は誘発されず, イソプロテレノール, ノルエピネフリンおよびエピネフリンを負荷した時点で, 単相性心室期外収縮が自然に出現するのみであった. 低酸素脳症のために運動負荷誘発試験は試行できなかった. QT延長症候群やBrugada症候群は否定的であった. 臨床経過よりカテコラミン誘発性心室頻拍が疑われ, 家族の強い希望で植込み型除細動器の植え込みを施行した.
    結語: カテコラミン誘発性心室頻拍と臨床的診断した1例であった. 若年の運動後, 意識消失の既往がある症例を診察する際には, 本症例を鑑別診断にあげる必要がある.
  • ペースメーカ植込み同胞例に認められた新たなLamin A/C変異
    佐野 幹, 渡邉 英一, 牧山 武, 内山 達司, 祖父江 嘉洋, 奥田 健太郎, 山本 真由美, 堀江 稔, 尾崎 行男
    心電図 31(1) 18-24 2011年
    中間径線維のひとつであるLamin A/Cは,核膜内膜を裏打ちして核膜構造を維持するとともに,遺伝子転写調節や遺伝子発現制御などの機能を有する.Lamin A/C遺伝子(LMNA)は,関節拘縮,骨格筋異常,および刺激伝導障害に伴う拡張型心筋症を3主徴とするEmery-Dreifuss型筋ジストロフィーの責任遺伝子として報告された.その後,関節拘縮や骨格筋異常を有さないものの,拡張型心筋症に刺激伝導障害を合併した症例にLMNA変異を認めることが報告され,Lamin関連心筋症とよばれる.本疾患は心不全に加え,心室性頻脈性不整脈による突然死が多いのを特徴とする.今回,われわれは,徐脈性不整脈の治療目的にペースメーカを植込まれた3同胞(ペースメーカ植込み時平均年齢49.6歳,男性:女性=1例:2例)に遺伝子検索を行い,新たなLMNA変異(Q258X)を認めたため,文献的な考察を加えて報告する.
  • フォーラム 第74回日本循環器学会総会・学術集会レポート(Vol.4)シンポジウム4 遺伝性不整脈の診断と治療(Inherited Arrhythmias: Diagnosis and Treatment)
    堀江 稔
    医学のあゆみ 233(7) 559-561 2010年05月
  • Emerging acute unilateral pulmonary edema in a patient with pheochromocytoma.
    Itsuko Miyazawa, Atsuyuki Wada, Toshiro Sugimoto, Norihisa Nitta, Minoru Horie
    Int J Cardiol 133(2) e50-51 2009年04月
    We report a patient who presented with unilateral pulmonary edema without cardiomegaly. Our patient was finally diagnosed as having pheochromocytoma crisis. © 2007 Elsevier Ireland Ltd. All rights reserved.
  • デスモゾーム病としての不整脈源性右室心筋症--デスモゾーム分子遺伝子異常 (第5土曜特集 心不全--研究と臨床の最前線) -- (心不全の先端的研究トピックス 心不全のジェネティクスとエピジェネティクス)
    堀江 稔
    医学のあゆみ 232(5) 588-592 2010年01月
  • Interaction between dietary marine-derived n-3 fatty acids intake and J-point elevation on the risk of cardiac death: A 24-year follow-up of Japanese men
    Takashi Hisamatsu, Takashi Hisamatsu, Takashi Hisamatsu, Katsuyuki Miura, Katsuyuki Miura, Takayoshi Ohkubo, Takayoshi Ohkubo, Takashi Yamamoto, Akira Fujiyoshi, Naoko Miyagawa, Aya Kadota, Naoyuki Takashima, Nagako Okuda, Yasuhiro Matsumura, Katsushi Yoshita, Yoshikuni Kita, Yoshitaka Murakami, Yoshitaka Murakami, Yasuyuki Nakamura, Tomonori Okamura, Minoru Horie, Akira Okayama, Hirotsugu Ueshima, Hirotsugu Ueshima
    Heart 99 1024-1029 2013年07月
    Objective: Higher marine-derived n-3 fatty acids (MDn3FAs) intake reduces the risk of sudden cardiac death via antiarrhythmic effects. The article evaluates whether MDn3FAs intake attenuates the increased risk of cardiac death associated with J-point elevation (JPE), characterised by an elevation of QRS-ST junction (J-point) ≥0.1 mV on electrocardiography. Design: A prospective population-based cohort study. Setting: The National Survey on Circulatory Disorders and the National Nutrition Survey of Japan. Participants: A total of 4348 community-dwelling men (mean age 49.3 years), without cardiovascular diseases at baseline, from randomly selected areas across Japan. Main outcome measures: Cardiac death (200 men) during the 24-year follow-up. Results: Dietary MDn3FAs intake was assessed using a dietary method to estimate individual intake of household-based weighed food records for 3 days. Cox models were used to calculate HRs and 95% CIs adjusted for possible confounding factors. JPE was present in 340 participants (7.8%). The median daily intake of MDn3FAs was 0.35%kcal (0.92 g/day). The risk of cardiac death was significantly higher in participants with JPE than in those without JPE in the low intake group ( < 0.35%kcal; adjusted HR 3.51; 95% CI 1.84 to 6.73; p < 0.001), but not in the high intake group (≥0.35%kcal; adjusted HR 1.09; 95% CI 0.56 to 2.16; p=0.795). The interaction between dietary MDn3FAs intake and JPE on the risk of cardiac death was statistically significant (p=0.006). Conclusions: The increased risk of cardiac death associated with JPE may be attenuated by higher dietary MDn3FAs intake.
  • 不整脈の遺伝子診断  2.家族性ペースメーカー植込み症例における遺伝的背景の検討―心臓Na`+´チャネル病,Lamin A/C遺伝子関連心筋症―:―心臓Na+チャネル病,Lamin A/C遺伝子関連心筋症―
    牧山 武, 静田 聡, 赤尾 昌治, 木村 剛, 堀江 稔
    心電図 30(3) 200-208 2010年
    洞不全症候群,房室ブロックに代表される徐脈性不整脈疾患は,加齢性変化にて多くみられるが,若年や家族性に認められる場合には遺伝的素因の関与が強く疑われる.今回われわれは,家族性徐脈性不整脈疾患の遺伝的背景を調べるために,家族性ペースメーカー植込み患者33症例(すべて発端者)を対象として候補遺伝子の網羅的スクリーニングを施行した.遺伝子解析の結果,33例中17例(51.5%)に心臓Na+チャネル遺伝子(SCN5A),またはLamin A/C遺伝子(LMNA)異常を同定した〔SCN5A異常8/33例(24.2%),LMNA異常9/33例(27.2%)〕.SCN5A異常を検出した8例中5例には,ほかの心臓Na+チャネル病の合併(Brugada症候群4例,QT延長症候群1例)を認めた.一方,LMNAは核膜の裏打ち蛋白であるLamin A,Cをコードし,その遺伝子異常により拡張型心筋症,心臓伝導障害,致死性心室性不整脈による突然死を引き起こす.本研究の結果,家族性ペースメーカー植込み患者には,突然死を引き起こし得る心臓Na+チャネル病(Brugada症候群,QT延長症候群)やLamin A/C遺伝子関連心筋症を合併している例が少なくないことがわかった.治療としては,ペースメーカー植込みではなく,植込み型除細動器や除細動機能付き両室ペーシング植込みが望ましい例もあり,家族性徐脈性不整脈症例における遺伝子解析の重要性が示唆された.
  • L-Type calcium channel mutations in Japanese patients with inherited arrhythmias
    Megumi Fukuyama, Seiko Ohno, Seiko Ohno, Qi Wang, Hiromi Kimura, Takeru Makiyama, Hideki Itoh, Makoto Ito, Minoru Horie
    Circulation Journal 77 1799-1806 2013年07月
    Background: Mutations in genes encoding the L-type cardiac calcium channel (LTCC) are associated with various types of inherited arrhythmias, including Brugada syndrome (BrS). However, the frequency in Asian populations remains unknown. This study aimed to elucidate disease-causing mutations in LTCC-related genes in Japanese patients diagnosed as BrS or idiopathic ventricular fibrillation (IVF), early repolarization syndrome, short QT syndrome, and compare them with those carrying SCN5A mutations. Methods and Results: We screened CACNA1C and CACNB2b in 312 probands and compared the clinical characteristics between probands with gene mutations in CACNA1C or SCN5A. In results, we identified 6 CACNA1C mutations in 7 unrelated probands and SCN5A mutations in 20 probands. There were no CACNB2b mutation carriers. In topology, half of the mutations were located in the C-terminus. Among 7 CACNA1C mutation carriers, 2 were female and 3 were symptomatic; 2 patients were resuscitated from ventricular fibrillation, and 1 patient had syncope. Compared with SCN5A mutation carriers, there were no significant differences in the ECG characteristics. 2 of 3 symptomatic CACNA1C patients were female, but all female SCN5A mutation carriers remained asymptomatic. Conclusions: We identified 6 CACNA1C mutations in BrS and IVF patients and their phenotypes were varied. Although mutation frequency was not high, screening of LTCC channel genes may be clinically important to prevent unexpected sudden death. (Circ J 2013; 77: 1799-1806).
  • 心血管疾患 (特集 全身疾患としてのCOPD)
    松本 鉄也, 中野 恭幸, 堀江 稔
    日本胸部臨床 67(12) 1000-1009 2008年12月
  • 家族性心臓伝導障害に同定されたconnexin 40遺伝子GJA5変異の機能異常
    蒔田 直昌, 住友 直方, 関 明子, 渡部 裕, 福原 茂朋, 牧山 武, 堀江 稔, 萩原 誠久, 望月 直樹, Jean-Jacques Schott
    心電図 30(3) 2010年
  • Restoration of aberrant conduction induced by premature ventricular contractions
    Hideki Hayashi, Takeshi Shibukawa, Minoru Horie
    Internal Medicine 52 1425 2013年06月
  • 不整脈の遺伝子診断  1.先天性QT延長症候群の遺伝子診断―複数変異症例の検討―:―複数変異症例の検討―
    伊藤 英樹, 清水 渉, 林 研至, 山形 研一郎, 坂口 知子, 大野 聖子, 牧山 武, 赤尾 昌治, 藍 智彦, 野田 崇, 宮崎 文, 宮本 恵宏, 山岸 正和, 鎌倉 史郎, 堀江 稔
    心電図 30(3) 195-199 2010年
    先天性QT延長症候群は,イオンチャネル蛋白に関連する遺伝子変異が原因で心筋再分極異常をきたし,QT延長と致死性不整脈を発症させる疾患である.通常遺伝子変異は単変異であるが,複数の変異を有する症例も報告されている.全国4施設で遺伝子変異が同定された612症例の先天性QT延長症候群を単変異574例(LQT1 259例,LQT2 251例,LQT3 62例,LQT5 2例)と複数変異38例に分類し,臨床像を比較検討した.遺伝子診断された314例の発端者のうち,28例(8.9%)が複数変異症例であった.全612例の解析において,QTc間隔は複数変異症例で有意に延長しており(複数変異症例vs.単変異症例;501±58 vs. 477±53 msec, p=0.014),発症年齢も若年であった(複数変異症例vs.単変異症例;10±7 vs. 18±16歳,p<0.001).β遮断薬の内服率は複数変異症例で有意に高率であった.40歳未満の心イベントはどのサブタイプの単変異症例より,複数変異症例で高率であった.以上から,複数変異症例を有するQT延長症候群例の臨床像は単変異症例より重篤であることが示唆された.
  • Is More Aggressive Prevention of Coronary Artery Disease Required for Patients With Early Repolarization Syndrome?: Reply
    Takashi Hisamatsu, Takashi Hisamatsu, Takayoshi Ohkubo, Katsuyuki Miura, Minoru Horie, Hirotsugu Ueshima, Hirotsugu Ueshima
    Circulation Journal 77 1643 2013年05月
  • Age-dependent clinical and genetic characteristics in Japanese patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia
    Seiko Ohno, Seiko Ohno, Iori Nagaoka, Megumi Fukuyama, Hiromi Kimura, Hideki Itoh, Takeru Makiyama, Akihiko Shimizu, Minoru Horie
    Circulation Journal 77 1534-1542 2013年05月
    Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a heart muscle disease caused by desmosomal gene mutations, and presents as ventricular tachycardia and sudden cardiac death. Although the mean age at onset or diagnosis of ARVC/D are reported to be around the 30-40 s, the age-dependent clinical and genetic differences remain unknown. Methods and Results: A total of 35 consecutive Japanese probands (23 male) who were clinically diagnosed with ARVC/D were enrolled in the present study, and genetic analysis of PKP2, DSP, DSG2, and DSC2 was done. The mean age at the first symptom and at diagnosis was 38.6±14.8 years and 40.5±17.7 years, respectively. Probands in whom the onset was cardiopulmonary arrest were significantly younger (22.3±15.3 years) than those with arrhythmia (41.1±13.2 years) or congestive heart failure (45.7±8.5 years). On genetic screening, 19 mutation carriers were identified. Although there was no age dependence for each gene mutation carrier, carriers with PKP2 premature stop codon developed the disease at a significantly younger age than other mutation carriers. Conclusions: The initial clinical manifestations in some young probands were very severe, and PKP2 mutations with a premature stop codon would be associated with disease onset at a younger age.
  • SCN5A mutation associated with ventricular fibrillation, early repolarization, and concealed myocardial abnormalities
    Hiroshi Watanabe, Kimie Ohkubo, Ichiro Watanabe, Taka Aki Matsuyama, Hatsue Ishibashi-Ueda, Nobue Yagihara, Wataru Shimizu, Minoru Horie, Tohru Minamino, Naomasa Makita
    International Journal of Cardiology 165 2013年05月
  • Association between J-point elevation and death from coronary artery disease: 15-year follow-up of the NIPPON DATA90
    Takashi Hisamatsu, Takashi Hisamatsu, Takayoshi Ohkubo, Takayoshi Ohkubo, Katsuyuki Miura, Takashi Yamamoto, Akira Fujiyoshi, Naoko Miyagawa, Aya Kadota, Naoyuki Takashima, Shin ya Nagasawa, Yoshikuni Kita, Yoshitaka Murakami, Akira Okayama, Minoru Horie, Tomonori Okamura, Hirotsugu Ueshima, Hirotsugu Ueshima
    Circulation Journal 77 1260-1266 2013年05月
    Background: An early repolarization pattern, characterized by an elevation of the QRS-ST junction (J-point) on 12-lead electrocardiography (ECG) is associated with cardiac and sudden death. However, little is known about the prognostic significance of J-point elevation for various disease-specific cardiovascular outcomes, including coronary artery disease (CAD). Methods and Results: To investigate the association between the presence of J-point elevation ≥0.1 mV and various disease-specific cardiovascular outcomes, we conducted a 15-year prospective study in a representative general Japanese population of 7,630 individuals (41% men, mean age 52.4 years) who participated in the National Survey of Circulatory Disorders. Cox models were used to estimate the hazard ratios (HRs) adjusted for possible confounding factors. J-point elevation was present in 264 individuals (3.5%) and was associated with an increased risk of cardiac death (adjusted HR, 2.54; 95% confidence interval [CI] 1.40-4.58; P=0.002) and death from CAD (adjusted HR, 4.66; 95% CI 2.30-9.46; P < 0.001). In a subgroup analysis by age, the association between J-point elevation and cardiovascular outcomes was more remarkable in middle-aged ( < 60 years) than in older individuals (≥60 years) (all P for interaction < 0.05). Conclusions: J-point elevation on standard 12-lead ECG was an independent predictor of cardiac death and death from CAD in a representative sample of the general Japanese population, particularly among the middle-aged.
  • CARTO (Up-to-Date Art&Technique 進化した3Dイメージング(前編)CT・MRIの見かた・撮りかた)
    小澤 友哉, 堀江 稔
    Circulation up-to-date 8(3) 270-279 2013年06月
  • Ultrastructural maturation of human-induced pluripotent stem cell-derived cardiomyocytes in a long-term culture
    Tsukasa Kamakura, Takeru Makiyama, Kenichi Sasaki, Yoshinori Yoshida, Yimin Wuriyanghai, Jiarong Chen, Tetsuhisa Hattori, Seiko Ohno, Toru Kita, Minoru Horie, Shinya Yamanaka, Takeshi Kimura
    Circulation Journal 77 1307-1314 2013年05月
    Background: In the short- to mid-term, cardiomyocytes generated from human-induced pluripotent stem cells (hiPSC-CMs) have been reported to be less mature than those of adult hearts. However, the maturation process in a long-term culture remains unknown. Methods and Results: A hiPSC clone generated from a healthy control was differentiated into CMs through embryoid body (EB) formation. The ultrastructural characteristics and gene expressions of spontaneously contracting EBs were analyzed through 1-year of culture after cardiac differentiation was initiated. The 14-day-old EBs contained a low number of myofibrils, which lacked alignment, and immature high-density Z-bands lacking A-, H-, I-, and Mbands. Through the long-term culture up to 180 days, the myofibrils became more tightly packed and formed parallel arrays accompanied by the appearance of mature Z-, A-, H-, and I-bands, but not M-bands. Notably, M-bands were finally detected in 360-day-old EBs. The expression levels of the M-band-specific genes in hiPSC-CMs remained lower in comparison with those in the adult heart. Immunocytochemistry indicated increasing number of MLC2v-positive/MLC2a-negative cells with decreasing number of MLC2v/MLC2a double-positive cells, indicating maturing of ventricular-type CMs. Conclusions: The structural maturation process of hiPSC-CMs through 1-year of culture revealed ultrastructural sarcomeric changes accompanied by delayed formation of M-bands. Our study provides new insight into the maturation process of hiPSC-CMs.
  • Novel SCN3B mutation associated with brugada syndrome affects intracellular trafficking and function of Nav1.5
    Taisuke Ishikawa, Naohiko Takahashi, Seiko Ohno, Harumizu Sakurada, Kazufumi Nakamura, Young Keun On, Jeong Euy Park, Takeru Makiyama, Minoru Horie, Takuro Arimura, Naomasa Makita, Akinori Kimura
    Circulation Journal 77 959-967 2013年04月
    Background: Brugada syndrome (BrS) is characterized by specific alterations on ECG in the right precordial leads and associated with ventricular arrhythmia that may manifest as syncope or sudden cardiac death. The major causes of BrS are mutations in SCN5A for a large subunit of the sodium channel, Nav1.5, but a mutation in SCN3B for a small subunit of sodium channel, Navβ3, has been recently reported in an American patient. Methods and Results: A total of 181 unrelated BrS patients, 178 Japanese and 3 Koreans, who had no mutations in SCN5A, were examined for mutations in SCN3B by direct sequencing of all exons and adjacent introns. A mutation, Val110Ile, was identified in 3 of 178 (1.7%) Japanese patients, but was not found in 480 Japanese controls. The SCN3B mutation impaired the cytoplasmic trafficking of Nav1.5, the cell surface expression of which was decreased in transfected cells. Whole-cell patch clamp recordings of the transfected cells revealed that the sodium currents were significantly reduced by the SCN3B mutation. Conclusions: The Val110Ile mutation of SCN3B is a relatively common cause of SCN5A-negative BrS in Japan, which has a reduced sodium current because of the loss of cell surface expression of Nav1.5.
  • A Nonsynonymous Polymorphism in Semaphorin 3A as a Risk Factor for Human Unexplained Cardiac Arrest with Documented Ventricular Fibrillation
    Yukiko Nakano, Yukiko Nakano, Kazuaki Chayama, Kazuaki Chayama, Hidenori Ochi, Hidenori Ochi, Masaaki Toshishige, Yasufumi Hayashida, Daiki Miki, Daiki Miki, C. Nelson Hayes, C. Nelson Hayes, Hidekazu Suzuki, Takehito Tokuyama, Noboru Oda, Kazuyoshi Suenari, Yuko Uchimura-Makita, Kenta Kajihara, Akinori Sairaku, Chikaaki Motoda, Mai Fujiwara, Yoshikazu Watanabe, Yukihiko Yoshida, Kimie Ohkubo, Ichiro Watanabe, Akihiko Nogami, Kanae Hasegawa, Hiroshi Watanabe, Naoto Endo, Takeshi Aiba, Wataru Shimizu, Seiko Ohno, Minoru Horie, Koji Arihiro, Satoshi Tashiro, Naomasa Makita, Yasuki Kihara
    PLoS Genetics 9 2013年04月
    Unexplained cardiac arrest (UCA) with documented ventricular fibrillation (VF) is a major cause of sudden cardiac death. Abnormal sympathetic innervations have been shown to be a trigger of ventricular fibrillation. Further, adequate expression of SEMA3A was reported to be critical for normal patterning of cardiac sympathetic innervation. We investigated the relevance of the semaphorin 3A (SEMA3A) gene located at chromosome 5 in the etiology of UCA. Eighty-three Japanese patients diagnosed with UCA and 2,958 healthy controls from two different geographic regions in Japan were enrolled. A nonsynonymous polymorphism (I334V, rs138694505A > G) in exon 10 of the SEMA3A gene identified through resequencing was significantly associated with UCA (combined P = 0.0004, OR 3.08, 95%CI 1.67-5.7). Overall, 15.7% of UCA patients carried the risk genotype G, whereas only 5.6% did in controls. In patients with SEMA3A I334V , VF predominantly occurred at rest during the night. They showed sinus bradycardia, and their RR intervals on the 12-lead electrocardiography tended to be longer than those in patients without SEMA3A I334V (1031±111 ms versus 932±182 ms, P = 0.039). Immunofluorescence staining of cardiac biopsy specimens revealed that sympathetic nerves, which are absent in the subendocardial layer in normal hearts, extended to the subendocardial layer only in patients with SEMA3A I334V . Functional analyses revealed that the axon-repelling and axon-collapsing activities of mutant SEMA3A I334V genes were significantly weaker than those of wild-type SEMA3A genes. A high incidence of SEMA3A I334V in UCA patients and inappropriate innervation patterning in their hearts implicate involvement of the SEMA3A gene in the pathogenesis of UCA. © 2013 Nakano et al.
  • Effects of flecainide on exercise-induced ventricular arrhythmias and recurrences in genotype-negative patients with catecholaminergic polymorphic ventricular tachycardia
    Hiroshi Watanabe, Christian Van Der Werf, Ferran Roses-Noguer, Arnon Adler, Naokata Sumitomo, Christian Veltmann, Raphael Rosso, Zahurul A. Bhuiyan, Hennie Bikker, Prince J. Kannankeril, Minoru Horie, Tohru Minamino, Sami Viskin, Björn C. Knollmann, Jan Till, Arthur A.M. Wilde
    Heart Rhythm 10 542-547 2013年04月
    Background: Conventional therapy with beta-blockers is incompletely effective in preventing arrhythmic events in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT). We have previously discovered that flecainide in addition to conventional drug therapy prevents ventricular arrhythmias in patients with genotype-positive CPVT. Objective: To study the efficacy of flecainide in patients with genotype-negative CPVT. Methods: We studied the efficacy of flecainide for reducing ventricular arrhythmias during exercise testing and preventing arrhythmia events during long-term follow-up. Results: Twelve patients with genotype-negative CPVT were treated with flecainide. Conventional therapy failed to control ventricular arrhythmias in all patients. Flecainide was initiated because of significant ventricular arrhythmias (n = 8), syncope (n = 3), or cardiac arrest (n = 1). At the baseline exercise test before flecainide, 6 patients had ventricular tachycardia and 5 patients had bigeminal or frequent ventricular premature beats. Flecainide reduced ventricular arrhythmias at the exercise test in 8 patients compared to conventional therapy, similar to that in patients with genotype-positive CPVT in our previous report. Notably, flecainide completely prevented ventricular arrhythmias in 7 patients. Flecainide was continued in all patients except for one who had ventricular tachycardia at the exercise test on flecainide. During a follow-up of 48±94 months, arrhythmia events (sudden cardiac death and aborted cardiac arrest) associated with noncompliance occurred in 2 patients. Flecainide was not discontinued owing to side effects in any of the patients. Conclusions: Flecainide was effective in patients with genotype-negative CPVT, suggesting that spontaneous Ca 2+ release from ryanodine channels plays a role in arrhythmia susceptibility, similar to that in patients with genotype-positive CPVT. © 2013 Published by Elsevier Inc. on behalf of Heart Rhythm Society.
  • Long-term follow-up of a pediatric cohort with short QT syndrome
    Juan Villafañe, Joseph Atallah, Michael H. Gollob, Philippe Maury, Christian Wolpert, Roman Gebauer, Hiroshi Watanabe, Minoru Horie, Olli Anttonen, Prince Kannankeril, Brett Faulknier, Jorge Bleiz, Takeru Makiyama, Wataru Shimizu, Robert M. Hamilton, Ming Lon Young
    Journal of the American College of Cardiology 61 1183-1191 2013年03月
    Objectives: The purpose of this study was to define the clinical characteristics and long-term follow-up of pediatric patients with short QT syndrome (SQTS). Background: SQTS is associated with sudden cardiac death. The clinical characteristics and long-term prognosis in young patients have not been reported. Methods: This was an international case series involving 15 centers. Patients were analyzed for electrocardiography characteristics, genotype, clinical events, Gollob score, and efficacy of medical or defibrillator (implantable cardioverter-defibrillator [ICD]) therapy. To assess the possible prognostic value of the Gollob score, we devised a modified Gollob score that excluded clinical events from the original score. Results: Twenty-five patients 21 years of age or younger (84% males, median age: 15 years, interquartile range: 9 to 18 years) were followed up for 5.9 years (interquartile range: 4 to 7.1 years). Median corrected QT interval for heart rate was 312 ms (range: 194 to 355 ms). Symptoms occurred in 14 (56%) of 25 patients and included aborted sudden cardiac death in 6 patients (24%) and syncope in 4 patients (16%). Arrhythmias were common and included atrial fibrillation (n = 4), ventricular fibrillation (n = 6), supraventricular tachycardia (n = 1), and polymorphic ventricular tachycardia (n =1). Si xteen patients (84%) had a familial or personal history of cardiac arrest. A gene mutation associated with SQTS was identified in 5 (24%) of 21 probands. Symptomatic patients had a higher median modified Gollob score (excluding points for clinical events) compared with asymptomatic patients (5 vs. 4, p = 0.044). Ten patients received medical treatment, mainly with quinidine. Eleven of 25 index cases underwent ICD implantation. Two patients had appropriate ICD shocks. Inappropriate ICD shocks were observed in 64% of patients. Conclusions: SQTS is associated with aborted sudden cardiac death among the pediatric population. Asymptomatic patients with a Gollob score of < 5 remained event free, except for an isolated episode of supraventricular tachycardia, over an average 6-year follow-up. A higher modified Gollob score of 5 or more was associated with the likelihood of clinical events. Young SQTS patients have a high rate of inappropriate ICD shocks. © 2013 by the American College of Cardiology Foundation.
  • Prognostic implications of progressive cardiac conduction disease
    Tamiro Kawaguchi, Hideki Hayashi, Akashi Miyamoto, Tomohide Yoshino, Atsushi Taniguchi, Nobu Naiki, Yoshihisa Sugimoto, Makoto Ito, Joel Q. Xue, Yoshitaka Murakami, Minoru Horie
    Circulation Journal 77 60-67 2013年01月
    Background: Progressive cardiac conduction disease (PCCD), characterized by temporal increase in PR interval and QRS duration, may be attributed to diverse pathophysiological mechanisms. This study aimed to investigate whether PCCD is associated with increased risk of cardiovascular morbidity and mortality. Methods and Results: Digital analysis of 12-lead ECG was performed to select patients with PCCD from among a database containing 359,737 ECGs. Long-term prognosis of PCCD was assessed in a large hospital-based population: 458 patients (341 males; mean age, 57.9±14.7 years) with PCCD were enrolled. During a mean followup of 13.3±6.4 year s, 109 patients were hospitalized for heart failure (HF), and there were 16 and 59 deaths from cardiovascular diseases and all causes, respectively. Multivariate Cox proportional hazards analysis confirmed (1) a significant association of temporal incremental rate of PR interval (≥2 ms/year) and QRS duration (≥3 ms/year) with HF hospitalization (hazard ratio [HR], 2.34; 95% confidence interval [CI] , 1.36-4.05; P=0.002 and HR, 2.08; 95% CI, 1.25-3.53; P=0.01, respectively) and (2) a significant association of temporal incremental rate of PR interval (≥4 ms/year) and QRS duration (≥5 ms/year) with cardiovascular mortality (HR, 6.9; 95% CI, 1.47-36.96; P=0.02 and HR, 4.31; 95% CI, 1.19-16.5; P=0.03, respectively). Conclusions: The severity of PCCD was independently and significantly associated with HF hospitalization and cardiovascular mortality.
  • Flecainide reduces ventricular arrhythmias via a mechanism that differs from that of β-blockers in catecholaminergic polymorphic ventricular tachycardia
    Kenichi Dochi, Hiroshi Watanabe, Mihoko Kawamura, Akashi Miyamoto, Tomoya Ozawa, Yuko Nakazawa, Takashi Ashihara, Seiko Ohno, Hideki Hayashi, Makoto Ito, Hisanori Sakazaki, Hiro Kawata, Hiroya Ushinohama, Richard H. Kaszynski, Tohru Minamino, Naokata Sumitomo, Wataru Shimizu, Minoru Horie
    Journal of Arrhythmia 29 255-260 2013年01月
    Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by episodic ventricular tachycardia induced by adrenergic stress. Although β-blockers are used as first-line therapy, their therapeutic effects are largely incomplete. Flecainide has recently been shown to modify the molecular defects in CPVT. The aim of this study was to investigate the effects of flecainide as an add-on to conventional therapy on exercise-induced ventricular arrhythmia and compare them with those of conventional therapy alone. Methods: The study included 5 CPVT patients with a mutation in RYR2. They experienced episodic arrhythmic events despite conventional β-blocker therapy and were therefore given flecainide in addition. The effects of the addition of flecainide therapy on ventricular arrhythmia during exercise testing were compared with those of conventional therapy alone. Results: Both β-blockers alone and with additional flecainide increased the maximal workload attained at the onset of ventricular arrhythmia; however, only flecainide increased the sinus rate at the onset of ventricular arrhythmias. Furthermore, flecainide increased the exercise capacity by preventing exercise-induced arrhythmias. During a follow-up period of 17 ± 2 months, 1 patient experienced recurrent arrhythmic episodes that were associated with noncompliance. All patients reported improvements in their ability to perform the activities of daily living. Conclusion: Flecainide effectively reduced ventricular arrhythmias via a mechanism that differs from that of β-blockers in genotype-positive patients with CPVT. The specific effects of flecainide may be critical in the improvement noted in the patients' ability to perform daily activities. © 2013 Japanese Heart Rhythm Society. Published by Elsevier B.V. All rights reserved.
  • Genetic screening of kCNJ8 in Japanese patients with J-wave syndromes or idiopathic ventricular fibrillation
    Qi Wang, Seiko Ohno, Koichi Kato, Megumi Fukuyama, Takeru Makiyama, Hiromi Kimura, Nobu Naiki, Mihoko Kawamura, Hideki Hayashi, Minoru Horie
    Journal of Arrhythmia 29 261-264 2013年01月
    Background: J-point elevation has been demonstrated to be associated with ventricular fibrillation (VF) and has been proposed as a cause of the J-wave syndrome (JWS). A mutation of KCNJ8, S422L, was reported as a culprit gene. This study aimed to determine the prevalence of KCNJ8 mutations in a Japanese population with JWS or idiopathic VF (IVF). Methods: A total of 230 probands with JWS and IVF underwent genetic screening of KCNJ8. To analyze and compare clinical and electrocardiographic characteristics, the probands were divided into 4 groups: Brugada (Br) pattern only, early repolarization (ER) pattern only, Br and ER patterns, and true IVF. Results: The results of the genetic analysis revealed no S422L or other KCNJ8 mutations and indicated no significant difference between the groups. Conclusion: The KCNJ8 mutation showed no association with JWS or IVF among our Japanese patients. © 2013 Japanese Heart Rhythm Society. Published by Elsevier B.V. All rights reserved.
  • Genetic basis of Brugada syndrome
    Minoru Horie, Seiko Ohno
    Journal of Arrhythmia 29 71-76 2013年01月
    Brugada syndrome (BrS) is associated with the familial sudden death syndrome, and more than 10 genes have been reported as causative for or modifiers of BrS. All gene mutations are related to functional changes of inward sodium or calcium currents or outward potassium currents. SCN5A was the first gene known to be associated with BrS; it encodes the a-subunit of the cardiac sodium channel. Approximately 20% of BrS patients in genotyped cases were found to carry SCN5A mutations. The frequency for other BrS-associated gene mutations is so low that genotype-phenotype correlations for these genes have not been studied to the same extent as SCN5A-related BrS. In some families with SCN5A mutations, the penetrance of the mutations is low, and pathophysiological changes in the right ventricular outflow tract were reported in patients with SCN5A mutations. Furthermore, the phenotypes of SCN5A-related BrS can overlap with other phenotypes, including long QT and sick sinus syndrome, thereby suggesting that SCN5A mutations might be modifiers for BrS, but they do not direct cause BrS. Here, we summarize the genetic background of BrS, with a particular focus on recent progress in this field. © 2013 Japanese Heart Rhythm Society. Published by Elsevier B.V. All rights reserved.
  • Letter by Hayashi et al regarding article, "early repolarization is an independent predictor of occurrences of ventricular fibrillation in the very early phase of acute myocardial infarctions"
    Hideki Hayashi, Minoru Horie
    Circulation: Arrhythmia and Electrophysiology 5 2012年12月
  • High-risk long QT syndrome mutations in the Kv7.1 (KCNQ1) pore disrupt the molecular basis for rapid K+ permeation
    Don E. Burgess, Daniel C. Bartos, Allison R. Reloj, Kenneth S. Campbell, Jonathan N. Johnson, David J. Tester, Michael J. Ackerman, Véronique Fressart, Véronique Fressart, Isabelle Denjoy, Isabelle Denjoy, Pascale Guicheney, Pascale Guicheney, Arthur J. Moss, Seiko Ohno, Minoru Horie, Brian P. Delisle
    Biochemistry 51 9076-9085 2012年11月
    Type 1 long QT syndrome (LQT1) is caused by loss-of-function mutations in the KCNQ1 gene, which encodes the K + channel (Kv7.1) that underlies the slowly activating delayed rectifier K + current in the heart. Intragenic risk stratification suggests LQT1 mutations that disrupt conserved amino acid residues in the pore are an independent risk factor for LQT1-related cardiac events. The purpose of this study is to determine possible molecular mechanisms that underlie the loss of function for these high-risk mutations. Extensive genotype-phenotype analyses of LQT1 patients showed that T322M-, T322A-, or G325R-Kv7.1 confers a high risk for LQT1-related cardiac events. Heterologous expression of these mutations with KCNE1 revealed they generated nonfunctional channels and caused dominant negative suppression of WT-Kv7.1 current. Molecular dynamics simulations of analogous mutations in KcsA (T85M-, T85A-, and G88R-KcsA) demonstrated that they disrupted the symmetrical distribution of the carbonyl oxygen atoms in the selectivity filter, which upset the balance between the strong attractive and K + -K + repulsive forces required for rapid K + permeation. We conclude high-risk LQT1 mutations in the pore likely disrupt the architectural and physical properties of the K + channel selectivity filter. © 2012 American Chemical Society.
  • Drug-induced QT-interval prolongation and recurrent torsade de pointes in a child with heterotaxy syndrome and KCNE1 D85N polymorphism
    Lisheng Lin, Hitoshi Horigome, Naoko Nishigami, Seiko Ohno, Minoru Horie, Ryo Sumazaki
    Journal of Electrocardiology 45 770-773 2012年11月
    We present a child case of heterotaxy syndrome (asplenia syndrome) after Fontan procedure that showed extreme prolongation of QT interval and torsade de pointes (TdP) after administration of sodium channel blockers for paroxysmal atrial tachycardia. Despite low serum concentration of the drugs, QT prolongation persisted and TdP attacks with unconsciousness recurred, possibly in association with junctional bradycardia and myocardial damage although he had never experienced QT prolongation during bradycardia before. Temporal cardiac pacing via a venous route to exclude possible implication of bradycardia in induction of TdP was difficult to apply due to total cavopulmonary connection (TCPC) circulation. Continuous intravenous administration of low-dose isoproterenol was started but an appropriate heart rate for prevention of TdP was difficult to obtain. Finally, we were urged to conduct implantation of a DDD pacemaker combined with ICD surgically with epicardial leads, resulting in successful suppression of TdP and syncope. Screening of the genotype disclosed the KCNE1 D85N polymorphism, which is known as one of the typical disease-causing gene variants in long-QT syndrome (LQTS). © 2012 Elsevier Inc.
  • Agranulocytosis immediately after oral administration of cibenzoline and dabigatran in a patient with paroxysmal atrial fibrillation
    Hideki Hayashi Dr., Katsuyuki Kitoh, Kenichi Mitsunami, Minoru Horie
    Internal Medicine 51 1987-1990 2012年08月
    This case report describes agranulocytosis immediately after oral administration of cibenzoline and dabigatran in a 70-year-old woman with paroxysmal atrial fibrillation (AF). No blasts were found in peripheral blood and bone marrow, and the white blood cell count increased abruptly by intravenous administration of granulocyte colony-stimulation factor, suggesting an allergic response caused by cibenzoline or dabigatran, or both. Though antiarrhythmic drugs with anticoagulation therapy are commonly used to treat paroxysmal AF, caution has to be paid to drug-induced agranulocytosis. © 2012 The Japanese Society of Internal Medicine.
  • Lipoprotein Particle Profiles by Nuclear Magnetic Resonance, Standard Lipids and Coronary Artery Calcification in a Japanese General Population: the Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA)
    第45回日本動脈硬化学会抄録 2013年
  • Using induced pluripotent stem cells to investigate cardiac phenotypes in Timothy syndrome
    Minora Horie
    Respiration and Circulation 60(5) 483-488 2012年05月
  • J-point elevation induced by double master two-step test
    Tomohide Yoshino, Hideki Hayashi, Ichiro Nakae, Minoru Horie
    Internal Medicine 51 1941 2012年07月
  • Prolonged ventricular asystole and acquired Brugada syndrome
    Minoru Horie, Yuko Nakazawa, Makoto Ito, Tomoya Ozawa
    Internal Medicine 51 1799 2012年07月
  • Phenotype variability in patients carrying KCNJ2 mutations
    Hiromi Kimura, Jun Zhou, Jun Zhou, Mihoko Kawamura, Hideki Itoh, Yuka Mizusawa, Wei Guang Ding, Jie Wu, Seiko Ohno, Takeru Makiyama, Akashi Miyamoto, Nobu Naiki, Qi Wang, Yu Xie, Tsugutoshi Suzuki, Shigeru Tateno, Yoshihide Nakamura, Wei Jin Zang, Makoto Ito, Hiroshi Matsuura, Minoru Horie
    Circulation: Cardiovascular Genetics 5 344-353 2012年06月
    Background- Mutations of KCNJ2, the gene encoding the human inward rectifier potassium channel Kir2.1, cause Andersen-Tawil syndrome (ATS), a disease exhibiting ventricular arrhythmia, periodic paralysis, and dysmorphic features. However, some KCNJ2 mutation carriers lack the ATS triad and sometimes share the phenotype of catecholaminergic polymorphic ventricular tachycardia (CPVT). We investigated clinical and biophysical characteristics of KCNJ2 mutation carriers with "atypical ATS." Methods and Results- Mutational analyses of KCNJ2 were performed in 57 unrelated probands showing typical (≥2 ATS features) and atypical (only 1 of the ATS features or CPVT) ATS. We identified 24 mutation carriers. Mutation-positive rates were 75% (15/20) in typical ATS, 71% (5/7) in cardiac phenotype alone, 100% (2/2) in periodic paralysis, and 7% (2/28) in CPVT. We divided all carriers (n±45, including family members) into 2 groups: typical ATS (A) (n±21, 47%) and atypical phenotype (B) (n±24, 53%). Patients in (A) had a longer QUc interval [(A): 695±52 versus (B): 643±35 ms] and higher U-wave amplitude (0.24±0.07 versus 0.18±0.08 mV). C-terminal mutations were more frequent in (A) (85% versus 38%, P < 0.05). There were no significant differences in incidences of ventricular tachyarrhythmias. Functional analyses of 4 mutations found in (B) revealed that R82Q, R82W, and G144D exerted strong dominant negative suppression (current reduction by 95%, 97%, and 96%, respectively, versus WT at-50 mV) and T305S moderate suppression (reduction by 89%). Conclusions- KCNJ2 gene screening in atypical ATS phenotypes is of clinical importance because more than half of mutation carriers express atypical phenotypes, despite their arrhythmia severity. © 2012 American Heart Association, Inc.
  • Response to letter regarding article, "electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization"
    Hiroshi Watanabe, Akihiko Nogami, Kimie Ohkubo, Hiro Kawata, Yuka Hayashi, Taisuke Ishikawa, Takeru Makiyama, Satomi Nagao, Nobue Yagihara, Naofumi Takehara, Yuichiro Kawamura, Akinori Sato, Kazuki Okamura, Yukio Hosaka, Masahito Sato, Satoki Fukae, Masaomi Chinushi, Hirotaka Oda, Masaaki Okabe, Akinori Kimura, Koji Maemura, Ichiro Watanabe, Shiro Kamakura, Minoru Horie, Yoshifusa Aizawa, Wataru Shimizu, Naomasa Makita
    Circulation: Arrhythmia and Electrophysiology 5 2012年04月
  • A connexin40 mutation associated with a malignant variant of progressive familial heart block type I
    Naomasa Makita, Akiko Seki, Naokata Sumitomo, Halina Chkourko, Shigetomo Fukuhara, Hiroshi Watanabe, Wataru Shimizu, Connie R. Bezzina, Can Hasdemir, Hideo Mugishima, Takeru Makiyama, Alban Baruteau, Estelle Baron, Minoru Horie, Nobuhisa Hagiwara, Arthur A.M. Wilde, Vincent Probst, Hervé Le Marec, Dan M. Roden, Naoki Mochizuki, Jean Jacques Schott, Mario Delmar
    Circulation: Arrhythmia and Electrophysiology 5 163-172 2012年02月
    Background-Progressive familial heart block type I (PFHBI) is a hereditary arrhythmia characterized by progressive conduction disturbances in the His-Purkinje system. PFHBI has been linked to genes such as SCN5A that influence cardiac excitability but not to genes that influence cell-to-cell communication. Our goal was to explore whether nucleotide substitutions in genes coding for connexin proteins would associate with clinical cases of PFHBI and if so, to establish a genotype-cell phenotype correlation for that mutation. Methods and Results-We screened 156 probands with PFHBI. In addition to 12 sodium channel mutations, we found a germ line GJA5 (connexin40 [Cx40]) mutation (Q58L) in 1 family. Heterologous expression of Cx40-Q58L in connexin-deficient neuroblastoma cells resulted in marked reduction of junctional conductance (Cx40-wild type [WT] , 22.2 ± 1.7 nS, n=14; Cx40-Q58L, 0.56 ± 0.34 nS, n=14; P < 0.001) and diffuse localization of immunoreactive proteins in the vicinity of the plasma membrane without formation of gap junctions. Heteromeric cotransfection of Cx40-WT and Cx40-Q58L resulted in homogenous distribution of proteins in the plasma membrane rather than in membrane plaques in ̃ 50% of cells; well-defined gap junctions were observed in other cells. Junctional conductance values correlated with the distribution of gap junction plaques. Conclusions-Mutation Cx40-Q58L impairs gap junction formation at cell-cell interfaces. This is the first demonstration of a germ line mutation in a connexin gene that associates with inherited ventricular arrhythmias and emphasizes the importance of Cx40 in normal propagation in the specialized conduction system. © 2012 American Heart Association, Inc.
  • Successful catheter ablation of bidirectional ventricular premature contractions triggering ventricular fibrillation in catecholaminergic polymorphic ventricular tachycardia with RyR2 mutation
    Takashi Kaneshiro, Yoshihisa Naruse, Akihiko Nogami, Hiroshi Tada, Kentaro Yoshida, Yukio Sekiguchi, Nobuyuki Murakoshi, Yoshiaki Kato, Hitoshi Horigome, Mihoko Kawamura, Minoru Horie, Kazutaka Aonuma
    Circulation: Arrhythmia and Electrophysiology 5 2012年02月
  • バイオマーカー
    蔦本 尚慶, 和田 直人, 山川 高哉, 伊部 邦宏, 酒井 宏, 河原 千穂, 堀江 稔
    日本内科学会雑誌 101(2) 345-353 2012年02月
    心不全診断・重症度評価・治療効果判定にバイオマーカーの果たす役割は大きい.今後,人口の高齢化に伴い心不全患者が増加し的確な診断と評価が重要になる.心不全は重症化すると予後不良であり,早期診断と治療が重要である.循環器疾患バイオマーカーの中でも,BNP,NT-proBNPは,慢性心不全ガイドラインにも述べられているように心不全の診断と評価に有用な心筋バイオマーカーであるが,腎機能など影響を及ぼす因子も考慮する必要がある.
  • Association of the use of proton pump inhibitors with adverse cardiovascular and bleeding outcomes after percutaneous coronary intervention in the Japanese real world clinical practice
    Takeshi Kimura, Takeshi Morimoto, Yutaka Furukawa, Yoshihisa Nakagawa, Kazushige Kadota, Masashi Iwabuchi, Satoshi Shizuta, Hiroki Shiomi, Tomohisa Tada, Junichi Tazaki, Yoshihiro Kato, Mamoru Hayano, Mitsuru Abe, Takashi Tamura, Manabu Shirotani, Shinji Miki, Mitsuo Matsuda, Mamoru Takahashi, Katsuhisa Ishii, Masaru Tanaka, Takeshi Aoyama, Osamu Doi, Ryuichi Hattori, Ryozo Tatami, Satoru Suwa, Akinori Takizawa, Yoshiki Takatsu, Masaaki Takahashi, Hiroshi Kato, Teruki Takeda, Jong Dae Lee, Ryuji Nohara, Chuwa Tei, Minoru Horie, Hirofumi Kambara, Hisayoshi Fujiwara, Kazuaki Mitsudo, Masakiyo Nobuyoshi, Toru Kita
    Cardiovascular Intervention and Therapeutics 26 222-233 2011年12月
    Previous studies have shown inconsistent results regarding the effects of concomitant use of clopidogrel and proton pump inhibitors (PPI) on cardiovascular outcomes. We sought to evaluate the clinical impact of PPI-use in patients treated with thienopyridines after percutaneous coronary intervention (PCI) in a large Japanese observational database. Among 12446 patients discharged alive on thienopyridines (ticlopidine 90. 4% and clopidogrel 9. 6%), 3223 patients were treated with PPIs and 9223 patients without PPI at the time of hospital discharge. The PPI group included more patients with co-morbidities than the non-PPI group. The adjusted hazard ratio (HR) of PPI-use for a composite of cardiovascular death, myocardial infarction, and stroke was 1. 26 (95% confidence interval (CI) 1. 09-1. 47, p = 0. 002). The adjusted HR of PPI-use for bleeding was 1. 26 (95% CI 1. 05-1. 52, p = 0. 013). Cardiovascular and bleeding outcomes were not different among the three groups receiving three different types of PPI. The negative effect of PPI on cardiovascular outcome was consistently seen in both drug-eluting stent (DES) [HR 1. 31 (95% CI 1. 07-1. 6, p = 0. 0097)] and non-DES strata [HR 1. 25 (95% CI: 0. 99-1. 57, p = 0. 057)] (Interaction p = 0. 79) despite the fact that the duration of thienopyridine administration was significantly longer in patients receiving DES. In conclusion, cardiovascular outcomes after PCI were significantly worse in patients with PPI than in patients without PPI in the Japanese real clinical practice. However, the observed poorer cardiovascular outcome in patients receiving PPI was most likely to be related to residual confounding and seemed not causally related to attenuation of antiplatelet effect of thienopyridine through interaction with PPI. © 2011 Japanese Association of Cardiovascular Intervention and Therapeutics.
  • Letter by Hayashi et al Regarding Article, "Heritability of Early Repolarization: A Population-Based Study"
    Hideki Hayashi, Minoru Horie
    Circulation: Cardiovascular Genetics 4 2011年10月
  • [108th Scientific Meeting of the Japanese Society of Internal Medicine: educational lecture: 3. Diagnosis and treatment of Japanese patients with Brugada syndrome].
    Minoru Horie
    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 100 2599-2604 2011年09月
  • 致死性不整脈症候群の病態解明に関する研究 : 臨床・基礎研究(ヒト疾患特異的人工多能性幹(iPS)細胞を用いた解析)
    木村 剛, 北 徹, 堀江 稔
    医科学応用研究財団研究報告 31 447-454 2012年
  • KCNE5 (KCNE1L) variants are novel modulators of brugada syndrome and idiopathic ventricular fibrillation
    Seiko Ohno, Dimitar P. Zankov, Dimitar P. Zankov, Wei Guang Ding, Hideki Itoh, Takeru Makiyama, Takahiro Doi, Satoshi Shizuta, Tetsuhisa Hattori, Akashi Miyamoto, Nobu Naiki, Jules C. Hancox, Jules C. Hancox, Hiroshi Matsuura, Minoru Horie, Minoru Horie
    Circulation: Arrhythmia and Electrophysiology 4 352-361 2011年06月
    Background-Brugada syndrome (BrS) has a significantly higher incidence among the male sex. Among genes coding ion channels and their modulatory proteins, KCNE5 (KCNE1L) is located in the X chromosome and encodes an auxiliary β-subunit for K channels. KCNE5 has been shown to modify the transient outward current (I to ), which plays a key role in determining the repolarization process in the myocardium. This study investigated whether KCNE5 mutations could be responsible for BrS and other idiopathic ventricular fibrillation (IVF). Methods and Results-In 205 Japanese patients with BrS or IVF who tested negative for SCN5A mutation, we conducted a genetic screen for KCNE5 variants. We identified 2 novel KCNE5 variants: p.Y81H in 3 probands and p.[D92E;E93X] in 1 proband from 4 unrelated families. Y81H was identified in 1 man and 2 women; D92E;E93X was found in a 59-year-old man. All probands received implantable cardioverter-defibrillators. Functional consequences of the KCNE5 variants were determined through biophysical assay using cotransfection with KCND3 or KCNQ1. In the experiments with KCND3, which encodes Kv4.3, I to was significantly increased for both KCNE5 variants compared to wild type. In contrast, there were no significant changes in current properties reconstructed by KCNQ1+wild type KCNE5 and the 2 variants. With the simulation model, both variants demonstrated notch-and-dome or loss-of-dome patterns. Conclusions-KCNE5 modulates I to , and its novel variants appeared to cause IVF, especially BrS, in male patients through gain-of-function effects on I to . Screening for KCNE5 variants is relevant for BrS or IVF. © 2011 American Heart Association, Inc.
  • 日本人一般男性における心疾患死亡リスクに対する早期再分極とn-3不飽和脂肪酸摂取量との交互作用の検討:NIPPON DATA80
    J Cardiol Jpn Ed(第60回日本心臓病学会抄録) -(-) 285-285 2012年
  • Microalbuminuria is associated with morning hypertension in hypertensive patients with glucose intolerance
    Shinji Tamaki, Yasuyuki Nakamura, Takeshi Kawashima, Jinya Matsui, Toshiyuki Kanamori, Minoru Horie
    Japanese Pharmacology and Therapeutics 39 209-215 2011年02月
    Objective: It is thought that morning blood pressure (BP) measurements at home are an important independent predictive factor of cerebrovascular and cardiovascular incidents. In addition, it is said that the appearance of microalbuminuria is a predictive factor of cardiovascular incidents. In this study, we investigated the association between microalbuminuria and morning BP at home. Methods: Subjects who had received medical treatment for hypertension in our outpatient clinic from October to December 2007 were enrolled. Of the 380 patients studied, which subjects gave informed consent for this study, 122 (32.1% ; 59 men, 63 women) showed glucose intolerance (fasting blood sugar (BS) ≧110 mg/dL and/or HbA1c≧5.8%) and 91 (41 men, 50 women) brought their home BP records to the outpatient clinic (74.6%). We examined the association between microalbuminuria and morning BP in these 91 patients. Results: There were 41 male patients (64.9±10.8 years old) and 50 female patients (67.0 ± 9.1 years old). Logistic analysis showed that age [odds ratio (OR) = 1.04 ; 95% confidence interval (CI) : 1.00-1.07 ; p < 0.01], SBP at the outpatient clinic (OR=0.94 ; 95%CI : 0.92-0.97 p < 0.01), sex (OR=0.96 ; 95%CI : 0.71-1.29 ; p=0.02) and microalbuminuria (OR= 1.69 ; 95%CI : 1.04-2.80 ; p < 0.01) were independent factors contributing to morning hypertension measurements at home. Conclusion: The contributing factors determining morning hypertension were : male gender, higher age, higher SBP at the outpatient clinic, and positive microalbuminuria. Microalbuminuria is known as a marker of disorders throughout the body. It is necessary to recommend more aggressive BP control for individuals with morning hypertension and glucose intolerance.
  • Carvedilol, a Non-Selective ß-with β-Blocker is Effective in Long QT Syndrome Type 2
    Hiromi Kimura, Yuka Mizusawa, Hideki Itoh, Akashi Miyamoto, Mihoko Kawamura, Tamiro Kawaguchi, Nobu Naiki, Yuko Oka, Seiko Ohno, Makoto Ito, Minoru Horie, Takeru Makiyama, Minoru Horie
    Journal of Arrhythmia 27 324-331 2011年01月
    Background: β-blockers offer the first line therapy in congenital long QT syndrome (LQTS), and are more effective to prevent the cardiac event in LQTS type 1 than in type 2 or 3. In contrast, left cardiac sympathetic denervation (LCSD) was shown to be highly effective in patients refractory to β-blockers. Total sympathetic ablation by LCSD indicates the addititional involvement of “-adrenoceptor-mediated pathway. In genotyped LQT2 patients, we therefore hypothesized that blockade of “-adrenoceptor in addition to β-adrenoceptor by carvedilol could reduce cardiac events more efficiently than other types of β-blockers. Methods and Results: The study population consisted of 51 genotyped LQT2 patients (18 males, 23 ± 11 years old). They were divided into 2 groups (group 1: 43 patients treated with selective β-blockers, group 2: 8 patients with carvedilol) and retrospectively analyzed the efficacy of the respective β-blocker therapy in suppressing cardiac events. Cardiac events were observed in 11 patients of group 1 (26%) but none in group 2 during a follow-up period of 83 ± 80 months (P = 0.098). Conclusions: Carvedilol may be a potentially beneficial therapy for genotyped LQT2 patients who are refractory to other β selective blockers. © 2011, Japanese Heart Rhythm Society. All rights reserved.
  • Effect modification of dietary n-3 fatty acids on cardiovascular mortality risk by resting heart rate general population:NIPPON DATA80
    ESC2012 -(-) --- 2012年
  • 日本における Brugada 症候群 : 診断と治療
    堀江 稔
    日本内科学会雑誌 100(9) 2599-2604 2011年09月
  • KCNJ2変異を伴う Andersen-Tawil 症候群の神経生理所見
    定 翼, 国分 則人, 堀江 稔, 岡部 百佳, 駒ヶ嶺 朋子, 平田 幸一
    臨床神経生理学 : Japanese journal of clinical neurophysiology 39(1) 18-23 2011年02月
  • Mutations of KCNE Gene Family in Inherited Arrhythmia Syndromes
    Minoru Horie, Seiko Ohno, Jie Wu, Dimitar Zankov, Futoshi Toyoda, Wei Guang Ding, Hiroshi Matsuura
    journal of arrhythmia 27 244 2011年01月
    KCNE gene family consists of five different short genes encoding the regulatory proteins with a single transmembrane domain. The first member of the family (KCNE1) was cloned in 1988 (Takumi et al.) and was named as MinK because it reproduced slowly-activated voltage-gated K currents when expressed in Xenopus oocytes. Later in 1996, MinK (or KCNE1) has been shown to dramatically affect the expression of KCNQ1 channel, which is pore-forming subunit for human slow component of delayed rectifier K currents (IKS). Both are expressed in heart and inner ear. The reconstituted KCNE1/KCNQ1 channels display extremely slow activation and deactivation kinetics with enhanced current amplitude, which are much closer to those of human IKS. In contrast, another KCNE member (KCNE3) makes the channel constitutively open, and others reduce its amplitude or modulate gating. Interaction of KCNE family members with ion channels is very promiscuous. They drastically affect other pore-forming subunits of K channels such as KCNH2, KCNB1 (Kv2.1), KCND2 (Kv4.2) and KCND3 (Kv4.3). As they alter expression level, gating kinetics and second messenger regulation, their mutations may cause ion channelopathy through the malfunction of channels responsible for normal heart rhythm. In this symposium dedicated to Prof. Hiraoka, we would like to focus on these mutations in KCNE gene family and present several typical cases including our own experiences - KCNE1/KCNH2, KCNE2/KCND3, and KCNE3/KCNQ1. © 2011, Japanese Heart Rhythm Society. All rights reserved.
  • Clinical and Genetic Features of Japanese Patient with Congenital Long QT Syndrome
    Hisaki Makimoto, Takeshi Aiba, Shiro Kamakura, Yoshihiro Miyamoto, Wataru Shimizu, Minoru Horie, Satoshi Ogawa, Yoshifusa Aizawa, Tohru Ohe, Masakazu Yamgagishi, Naomasa Makita, Takeru Makiyama
    journal of arrhythmia 27 249 2011年01月
    Backgrounds: Genotype-phenotype aspects in Japanese patients (pts) with congenital long QT syndrome (LQTS) have not been fully elucidated. Methods and Results: Genotyped LQTS patients from Japanese multicenter registry (402 LQT1, 381 LQT2, and 113 LQT3 pts) were investigated. Age at first cardiac event (CE) was significantly lower and corrected QT (QTc) interval was significantly shorter in LQT1 than in LQT2 and LQT3 (13±14, 19±15, 17±20 yo; P=0.0004, 475± 46, 489±46, 482±58 ms; P=0.0003). Notched T wave (NTW) was more frequently observed in LQT2 (77%) than in LQT1 (9%) and LQT3 (10%). T wave alternance (TWA) was more frequently found in LQT3 (13%) compared with LQT1 (4%) and LQT2 (6%). Multivariate Cox-regression demonstrated that LQT1 and LQT2 pts with pore-site mutation and LQT3 pts with transmembrane mutation had significantly higher CE rate than those without (HR=1.52, 1.63, and 4.67, respectively). TWA (HR=2.37) in LQT1, longer QTc (HR=1.06 for QTc/10ms) and NTW (HR=1.51) in LQT2, and longer QTc (HR=1.11), NTW (HR=3.26), and TWA (HR=2.51) in LQT3 were independent risk factors of CE. Conclusions: In addition to mutations located in transmembrane region, some electrocardiographic parameters can be available as predictors of cardiac events in 3 genotypes of Japanese LQTS. © 2011, Japanese Heart Rhythm Society. All rights reserved.
  • A Weak Dominant Negative Mutation of KCNQ1-G269S Affects PKA-Mediated Up-Regulation of IKS Channels and Causes Adrenergic Triggered Long QT Syndrome
    Jie Wu, Nobu Naiki, Wei Guang Ding, Hiroshi Matsuura, Minoru Horie
    journal of arrhythmia 27 414 2011年01月
    Congenital Long QT Syndrome (LQTS) is an ion channelopathy characterized by QT interval prolongation in the ECG and ventricular tachyarrhythmias. It is caused by at least 13 types of gene mutations, among which the KCNQ1 gene mutation is most frequent and responsible for the LQT1. We identified a KCNQ1-G269S mutation in 11 patients from 4 families. Clinical data showed that most of patients were asymptomatic. Exercise stress test, however, prolonged their QTc intervals significantly. We engineered a G269S mutation by using PCR based mutagenesis and transfected into CHO or HEK293 cells together with KCNE1 by lipofectamine method. The whole cell IKS mutant currents were checked up using the patch-clamp technique. Co-expression of G269S decreased IKS currents in a mutant concentration-dependent manner, shifted the I-V relationship of IKS currents to more depolarizing direction, and accelerated the deactivation time of the currents. We found that G269S was a trafficking-refractory mutation and that the IKS reconstituted by G269A alone or the co-expression of wild type (WT) + G269S lost their response to β-adrenergic stimulation. Thus G269S mutation (1) exerted weak dominant-negative suppression effects on WT KCNQ1 channels; (2) coassembled with WT subunits to form tetramers and altered their gating kinetics and (3) may be associated with exercise-dependent unmasking of QTc prolongation. © 2011, Japanese Heart Rhythm Society. All rights reserved.
  • Long QT Syndromes Are Heterogeneous Disease Entities Presenting not only QT Prolongation but Multiple Phenotypes - Cases with Compound Heterozygous Mutations
    Minoru Horie, Hideki Itoh, Seiko Ohno, Takeru Makiyama, Wataru Shimizu, Shiro Kamakura, Kenshi Hayashi, Masakazu Yamagishi
    journal of arrhythmia 27 248 2011年01月
    Long QT syndromes (LQTS) consist of heterogeneous disease entities characterized by a remarkable prolongation of QT interval on ECG and a peculiar polymorphic ventricular tachycardia called “torsade de pointes”, which often degenerates into ventricular fibrillation and causing cardiogenic syncope or sudden death. Because of extensive studies on familial LQTS patients using the molecular genetics since early 1990s, it has been shown that genetic variants in genes encoding cardiac ion channels or their modulating proteins cause the delayed repolarization of ventricular action potential and thereby QT prolongation as a phenotype. Up to date, a variety of mutations in 13 different genes have been shown to be associated with LQTS. In the clinical setting, however, the first three subtypes (LQT1-3) are most frequently seen and presenting quite different phenotypes. Because the gene responsible for each subtype encodes a distinct ion current (I Ks , I Kr and I Na ), it is no wonder that the malfunction of specific channel leads to different clinical features. On a thorough screen for candidate genes in our multicenter study, in addition, we recognized that there were a substantial number of compound mutation cases (26 among 310 probands, 8.4%). In this symposium, we would like to make a brief overview on Japanese LQTS. © 2011, Japanese Heart Rhythm Society. All rights reserved.
  • Mutation Analysis of the KCNJ8 Gene in Japanese Patients with J-Wave Syndrome and Idiopathic Ventricular Fibrillation
    Wang Qi, Seiko Ohno, Takeru Makiyama, Hiromi Kimura, Nobu Naiki, Mihoko Kawamura, Koichi Kato, Minoru Horie
    journal of arrhythmia 27 415 2011年01月
    Background: Ventricular fibrillation (VF) is the most malignant arrhythmia causing the cardiac sudden death. Recently, the concept of J-wave syndrome (JWS), including the Brugada syndrome(BrS), has been proposed and early repolarization (J-point elevation) has been focused as one of clinical signs suggesting the primary electrical disease. A mutation of KCNJ8, S422L, was reported as the cause of JWS. In Japanese population with JWS or IVF, however, the prevalence of KCNJ8 mutations remains unknown. Method and Result: We screened KNCJ8 in 228 Japanese patients. They consisted of IVF patients with or without JWS (n=38) and asymptomatic JWS (mainly BrS, n=190), who were all negative for SCN5A mutation. The IVF group comprised 10 females and 28 males, and asymptomatic JWS group comprised 21 females and 169 males. In this cohort, we identified neither reported KCNJ8-S442L mutation nor other mutations including synonymous ones, using the denaturing high-performance liquid chromatography and the subsequent direct sequencing analysis. Conclusion: No KCNJ8 mutations were found in our Japanese IVF and asymptomatic JWS patients. Therefore KCNJ8 appears not to be the major gene responsible for IVF and asymptomatic JWS in Japan. © 2011, Japanese Heart Rhythm Society. All rights reserved.
  • Recent Advancement of Treatment in Catecholaminergic Polymorphic Ventricular Tachycardia
    Naokata Sumitomo, Wataru Shimizu, Hitoshi Horigome, Yoshihide Nakamura, Yoshio Arakaki, Harumizu Sakurada, Hiroshi Watanabe, Hiromitsu Nishizaki, Shiro Kamakura, Minoru Horie, Masayasu Hiraoka
    journal of arrhythmia 27 417 2011年01月
    Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is malignant arrhythmia characterized physical induced bidirectional or polymorphic ventricular tachycardia (VT). Methods and Results: From the Japanese registry of CPVT, 69 patients (M:F=25:44, age=11.7± 7.8years) were enrolled in this study. These patients were divided into 35 patients who were diagnosed during 1900s and 34 patients after 2000s. The incidence of sustained VT, nonsustained VT, and VF (10:22:3vs7:24:0, ns), the type of VT, and the rate of VT (194±29vs196±58, ns) were not different in these 2 groups. However, there was no sudden death in 2000s group, but 8 patients were died in 1900s group (p=0.003). Although statistically insignificant, there was no sudden death in 7 patients who was diagnosed over 20 year-old, however 8 of 62 patients were died who was diagnosed before 20 year-old. Conclusion: The prognosis of CPVT was markedly improved in the last 2 decade. This may be the result of propagation of the necessity of the restriction of exercise in the patients with CPVT, and also from the recent advancement of the use of antiarrhythmic medication, such as flecainide. The patients who were first diagnosed in adulthood may have better prognosis than the patients who were diagnosed in childhood. © 2011, Japanese Heart Rhythm Society. All rights reserved.
  • Site-Specific Arrhythmogenesis in Structurally Normal Heart of Non-Brugada Patients with Ventricular Arrhythmias Originating from Ventricular Outflow Tract
    Tomoya Ozawa, Makoto Ito, Hideki Itoh, Yuko Nakazawa, Yoshihisa Sugimoto, Takenori Yao, Akashi Miyamoto, Takashi Ashihara, Minoru Horie
    journal of arrhythmia 27 419 2011年01月
    Background: Ventricular fibrillation (VF) and/or polymorphic ventricular tachycardia (PVT) may be initiated by premature ventricular contractions (PVCs) from right ventricular outflow tract (RVOT). Methods: We evaluated the number and the location of PVCs/VTs foci of the 87 patients (mean age 43y, 54 females) who underwent radiofrequency ablation (RF) to the RVOT or coronary cusp without structural heart disease or Brugada syndrome. Results: Endocardial mapping showed no scar or low voltage area from RVOT during sinus rhythm. Seventy-five patients had monomorphic PVCs/VTs and exhibited no PVT or VF during both Holter monitors and RF. In 12 patients with PVCs of different morphologies, 9 patients had multiple PVCs originated from only RVOT septal area, and showed no PVT/VF. However, the other 3 patients had PVCs from both RVOT septum and free wall origins, and exhibited PVT and VF. Moreover, PVTs/VFs were triggered by spontaneous PVCs from only free wall foci of RVOT in those 3 patients. Conclusions: PVCs from free wall RVOT origin may induce malignant VT/VF in patients with idiopathic RVOT tachy-arrhythmias from multiple foci of both septal and free wall areas. Site-specific arrhythmogenesis presents in such patients. © 2011, Japanese Heart Rhythm Society. All rights reserved.
  • Plasma brain natriuretic peptide as a useful biomarker of heart failure
    Takayoshi Tsutamoto, Minoru Horie
    Nippon Rinsho 4 417-425 2007年04月
  • A novel SCN5A mutation associated with the linker between III and IV domains of Nav1.5 in a neonate with fatal long QT syndrome
    Kenichiro Yamamura, Jun Muneuchi, Kiyoshi Uike, Kazuyuki Ikeda, Hirosuke Inoue, Yasushi Takahata, Yuichi Shiokawa, Yukako Yoshikane, Takeru Makiyama, Minoru Horie, Toshiro Hara
    International Journal of Cardiology 145 61-64 2010年11月
  • Mutations of the Cardiac Ryanodine Recepter (RyR2) Gene in Catecholaminergic Polymorphic Ventricular Tachycardia
    Mihoko Kawamura, Iori Nagaoka, Kenichi Dohchi, Yukiko Nishio, Hideki Itoh, Hiromi Kimura, Akashi Miyamoto, Yuka Mizusawa, Yuko Jito, Katsuya Ishida, Makoto Ito, Takeru Makiyama, Seiko Ohno, Naokata Sumitomo, Kotaro Oyama, Minoru Horie
    journal of arrhythmia 27 187 2011年01月
    In 20cases with clinically-diagnosed catecholaminergic polymorphic ventricular tachycardia (CPVT) from 12 unrelated Japanese families, we conducted genetic testing on RyR2, a gene encoding the cardiac ryanodine receptor. The correlation between RyR2 - mutations and clinical phenotypes was investigated. The RyR2 mutations were found in 9 cases from the 20 probands (incidence: 45.0%) and in 3 from the 12 family members manifesting CPVT (incidence: 25.0%) Both bidirectional ventricular tachycardia (bVT) and atrial arrhythmias were Significantly more frequent in RyR2-positive compared to RyR2-negative CPVT patients. The fi ndings suggested that RyR2 mutations are closely related with bVT and atrial arrhythmias of early onset. © 2011, Japanese Heart Rhythm Society. All rights reserved.
  • Detection and prevalence of chronic obstructive pulmonary disease in a cardiovascular clinic: Evaluation using a hand held FEV1/FEV6meter and questionnaire
    Hiroshi Wada, Yasutaka Nakano, Taishi Nagao, Makoto Osawa, Hideto Yamada, Chikara Sakaguchi, Tetsuya Matsumoto, Takayoshi Tsutamoto, Makoto Ito, Minoru Horie
    Respirology 15 1252-1258 2010年11月
    Background and objective: COPD is one of the leading causes of morbidity and mortality worldwide, and its prevalence continues to increase. Although spirometry is indispensable for the diagnosis of COPD, other simple and reliable tools are necessary for screening of COPD because spirometry is not widely available. This study investigated the usefulness of a combination of an electronic FEV 1 /FEV 6 meter (PiKo-6) with a COPD questionnaire as a screening method in patients with cardiovascular diseases. Methods: The PiKo-6 and the COPD questionnaire of the International Primary Care Airways Group were used to screen patients attending a cardiovascular outpatient clinic. Patients with FEV 1 /FEV 6 < 70% were defined as having airflow limitation. Patients diagnosed with airflow limitation underwent spirometry. Using data from the PiKo-6 and the COPD questionnaire, patients were assigned to a COPD group or a non-COPD group. The relationship between PiKo-6 measurements and spirometry was also evaluated. Results: Among 753 patients, 82 (10.9%) showed airflow limitation when assessed with the PiKo-6. Of these patients, 79 (10.5%) were assigned to the COPD group. FEV 1 , FEV 6 and FEV 1 /FEV 6 , as measured with the PiKo-6, correlated significantly with FEV 1 , FVC and FEV 1 /FVC, respectively, as measured by spirometry (r=0.865, 0.751 and 0.57). Among the cardiovascular comorbidities, heart failure and ischaemic heart disease showed slightly stronger associations with airflow limitation (13.8% and 12.5%, respectively). Conclusions: Combination of the PiKo-6 with a COPD questionnaire may be a useful and feasible method of identifying undiagnosed COPD patients attending a cardiovascular outpatient clinic. This study shows for the first time that the combination of an electronic, hand held FEV 1 /FEV 6 meter with a COPD questionnaire is a useful and feasible method for identifying undiagnosed COPD among patients with cardiovascular diseases attending a cardiovascular outpatient clinic. © Asian Pacific Society of Respirology.
  • Ventricular Fibrillation Triggered during Radiofrequency Energy Delivery for Verapamil-Sensitive Idiopathic Left Ventricular Tachycardia
    Tomoya Ozawa, Makoto Ito, Yuko Nakazawa, Takashi Ashihara, Akashi Miyamoto, Minoru Horie, Yoshihisa Sugimoto, Takenori Yao
    journal of arrhythmia 27 208 2011年01月
    Verapamil-sensitive idiopathic left ventricular tachycardia (VT) can be suppressed by radiofrequency ablation (RF) on the Purkinje network. RF delivered on the Purkinje fi bers triggers premature ventricular contractions or repetitive ventricular response and disappear after cessation of RF. We present a case with idiopathic left VT who represented ventricular fibrillation (VF) during RF on the Purkinje network. Case: A 15-year-old male admitted our hospital because of recurrent sustained VT with QRS morphology of right bundle branch block and left axis deviation. Intravenous verapamil terminated VT. However, electrophysiologic study could not induce VT even if isoproterenol infusion. We delivered RF energy at the distal left posterior fascicular region where Purkinje potentials were recorded during sinus rhythm with pace-mapping QRS morphology mimicking VT-QRS. Shortly after RF delivery, polymorphic VT induced and degenerated into VF. RF deliveries around the VF site induced similar responses. Then, we created RF lesions on the Purkinje fibers more proximal to the VF-induced sites. No VT was documented 3 years after ablation. Conclusion: Purkinje network appears to have potential role for VF induction. RF ablations at the proximal site of the critical Purkinje network can prevent VT/VF occurrence in such case. © 2011, Japanese Heart Rhythm Society. All rights reserved.
  • Effect of eplerenone versus spironolactone on cortisol and hemoglobin A1c levels in patients with chronic heart failure
    Masayuki Yamaji, Takayoshi Tsutamoto, Chiho Kawahara, Keizo Nishiyama, Takashi Yamamoto, Masanori Fujii, Minoru Horie
    American Heart Journal 160 915-921 2010年11月
    Background: It has been reported that mineralocorticoid receptor antagonist improves the prognosis of chronic heart failure (CHF). Recently, hemoglobin A1c (HbA 1c ) levels have been reported to be an independent risk factor for mortality in CHF, suggesting the important role of insulin resistance in CHF. We compared the metabolic effect of a selective mineralocorticoid receptor blocker eplerenone with spironolactone in CHF patients. Methods: One hundred seven stable outpatients with mild CHF, who were already receiving standard therapy for CHF, were randomized (1:2) to spironolactone (25 mg/d) or eplerenone (50 mg/d). Plasma levels of B-type natriuretic peptide, adiponectin, HbA 1c and cortisol were measured before and after 4 months treatment with spironolactone or eplerenone. Results: There were no differences in baseline characteristics including hemodynamic parameters and plasma levels of biomarkers between 2 groups. In both groups, plasma B-type natriuretic peptide levels were significantly decreased and plasma aldosterone levels were significantly increased after 4 months. In patients receiving spironolactone (n = 34), plasma adiponectin levels were significantly decreased (12.6 ± 1.4-11.2 ± 1.3 μg/mL, P < .0001) and HbA 1c and cortisol levels were significantly increased (5.61 ± 0.1-5.8 ± 0.1%, P < .0001, 11.3 ± 0.8-14.7 ± 1.3 μg/dL, P = .003, respectively). In patients receiving spironolactone, there was a significant positive correlation between the change in cortisol and the change in HbA 1c (r = 0.489, P = .003). In contrast, in patients receiving eplerenone (n = 73), plasma levels of adiponectin, HbA 1c and cortisol did not change. Conclusion: These findings indicated that the metabolic effect of eplerenone differed from that of spironolactone and that eplerenone had a superior metabolic effect especially on HbA 1c in CHF patients. © 2010 Mosby, Inc.
  • 6.包括的管理・治療 5.アテローム血栓症を有する外来患者における1年追跡による循環器イベント発生率の検討(REACH Registry)
    血栓と循環 19(3) 219-221 2011年
  • カテコラミン誘発性多形性心室頻拍を疑う患者における遺伝子変異の検討 : 心筋リアノジン受容体について
    川村 美朋子, 長岡 伊織, 道智 賢市, 西尾 由貴子, 伊藤 英樹, 木村 紘美, 宮本 証, 水澤 有香, 地藤 優子, 石田 勝也, 伊藤 誠, 牧山 武, 大野 聖子, 住友 直方, 小山 耕太郎, 堀江 稔
    心電図 = Electrocardiology 30(4) 298-305 2010年10月
    本研究は,臨床的にカテコラミン誘発性多形性心室頻拍(CPVT)が疑われる20例とその家族12例を対象に,心筋リアノジン受容体(RyR2)の遺伝子解析を行った.またRyR2遺伝子異常の有無による臨床症状の相違について検討した.発端者20例のうち9例(同定率:45.0%),家族12例のうち3例(同定率:25.0%)においてRyR2の遺伝子変異を認めた.
    RyR2変異を認めたCPVT患者には二方向性心室頻拍(bVT)が有意に多く(感度:77%,特異度:72%),QT間隔の延長のないQT延長症候群(特にtype1)との区別に有用と考えられた.またRyR2の遺伝子変異を有するCPVT患者において心房不整脈が有意に認められ,RyR2と若年性の心房不整脈の関与が示唆された.
  • 高血圧と不整脈--高血圧の治療によって不整脈発症の予防は可能か? (特集 ライフスタイルと不整脈のかかわりを探る)
    堀江 稔
    Life style medicine 4(4) 322-326 2010年10月
  • P wave and the development of atrial fibrillation
    Katsuya Ishida, Hideki Hayashi, Akashi Miyamoto, Yoshihisa Sugimoto, Makoto Ito, Yoshitaka Murakami, Minoru Horie
    Heart Rhythm 7 289-294 2010年03月
    Background: Terminal P-wave inversion in lead V 1 representing left atrial overload has been considered a precursor of atrial fibrillation (AF). Objective: The purpose of this study was to determine whether this P-wave morphologic characteristic can predict the development of AF. Methods: Digital analysis of 12-lead ECGs was performed to enroll patients with P terminal force ≥0.06 s × 2 mm in lead V 1 from among a database of 308,391 ECG recordings. The prognostic value of ECG characteristics for developing AF was determined. Results: A total of 78 patients (mean age 52 ± 19 years) with left atrial overload were chosen from among 102,065 patients in the database. During mean follow-up of 43 months, 15 (19%) patients developed AF (AF group) versus 63 (81%) patients who did not (non-AF group). No significant difference was noted between the AF and non-AF groups with regard to the area, duration, and amplitude of the P-wave terminal portion in lead V 1 . In contrast, the area, duration, and amplitude of the P-wave initial portion in the same lead were significantly greater in the AF group than in the non-AF group (114.6 ± 73.0 μV × ms vs 73.1 ± 59.3 μV × ms, 42.2 ± 12.4 ms vs 35.7 ± 10.1 ms, and 94.0 ± 39.9 μV vs 68.8 ± 49.4 μV, respectively; P < .05 for each). Multivariate analysis confirmed that the area of the P-wave initial portion was independently associated with the development of AF (hazard ratio 4.02, 95% confidence interval 1.25-17.8; P = .018). Conclusion: P-wave initial portion in lead V 1 was an independent risk stratifier of AF development in patients with marked left atrial overload. © 2010 Heart Rhythm Society.
  • 遺伝性不整脈の診断と治療におけるiPS細胞利用の可能性 (臨床遺伝子学'10)
    堀江 稔
    最新医学 65(0) 2095-2101 2010年09月
  • Dose-dependent prognostic effect of carvedilol in patients with chronic heart failure: Special reference to ranscardiac gradient of norepinephrine (Circulation Journal (2009), 73, (2270-2275))
    Keizo Nishiyama, Takayoshi Tsutamoto, Masayuki Yamaji, Chiho Kawahara, Takashi Yamamoto, Masanori Fujii, Minoru Horie
    Circulation Journal 74 385 2010年02月
  • QT短縮症候群 (第1土曜特集 ここまで進んだ 不整脈研究の最新動向) -- (心室細動をめぐる新展開)
    堀江 稔
    医学のあゆみ 234(6) 719-722 2010年08月
  • 肺静脈隔離術後の心房細動再発検出における携帯型心電計の有用性
    中澤 優子, 芦原 貴司, 八尾 武憲, 城 日加里, 伊藤 英樹, 杉本 喜久, 伊藤 誠, 堀江 稔
    心電図 = Electrocardiology 30 "S-1-7" 2010年05月
  • 心電学研究の進歩(循環器学2009年の進歩)
    堀江 稔
    循環器専門医 : 日本循環器学会専門医誌 18(1) 90-95 2010年03月
  • 座談会「循環器病学の将来展望--基礎と臨床の融合」 iPS細胞利用の心筋再生などに期待--循環器疾患各領域で画期的な治療法開発が進む
    北 徹, 澤 芳樹, 堀江 稔
    MD 7(1) 8-17 2010年01月
  • 遺伝子異常と不整脈 (特集 危険な不整脈--みきわめ方と正しい対応)
    伊藤 英樹, 堀江 稔
    臨牀と研究 87(1) 98-101 2010年01月
  • 座談会 冠動脈疾患の治療を考える~JSHガイドライン改正を受けて~
    血圧 17 35-40 2010年
  • 肺静脈隔離手術後の心房細動再発検出における携帯型心電機の有用性。
    心電図 30(S-1) 71 2010年
  • Effect of carperitide on plasma adiponectin levels in acute decompensated heart failure patients with diabetes mellitus
    Masayuki Yamaji, Takayoshi Tsutamoto, Toshinari Tanaka, Chiho Kawahara, Keizo Nishiyama, Takashi Yamamoto, Masanori Fujii, Minoru Horie
    Circulation Journal 73 2264-2269 2009年12月
    Background: It is reported that adiponectin has a cardioprotective effect and is decreased in type 2 diabetes mellitus (DM). Methods and Results: The effect of carperitide (atrial natriuretic peptide: ANP) on plasma adiponectin levels was evaluated in acute decompensated heart failure (ADHF) patients with and without DM. In 47 patients (DM: n= 11) who were admitted with ADHF, blood samples were collected before and 7 days after administration of carperitide. The plasma levels of ANP, brain natriuretic peptide (BNP), aldosterone and adiponectin were measured. Plasma adiponectin levels were significantly increased (17.6±1.5 to 19.6±1.8μg/ml, P=0.0003) concomitant with the increase in ANP and decrease in BNP 7 days after carperitide infusion. Although adiponectin levels before treatment were slightly lower in ADHF patients with DM, the % increase in adiponectin levels was significantly greater in ADHF patients with DM than in those without DM (26.7 vs 6.6%, P=0.007). In the stepwise multi-variate analyses, a higher plasma aldosterone levels before treatment (P=0.04) and DM (P=0.01) were significant independent predictors of a greater % increase in adiponectin levels after treatment with carperitide. Conclusions: Carperitide infusion increases the plasma adiponectin level, especially in ADHF patients with DM.
  • 先天性QT延長症候群の遺伝子診断―複数異変症例の検討―
    心電図 30(2) 195-199 2010年
  • Effect of carvedilol on plasma adiponectin concentration in patients with chronic heart failure: Reply
    Masayuki Yamaji, Takayoshi Tsutamoto, Toshinari Tanaka, Keizo Nishiyama, Chiho Kawahara, Masanori Fujii, Takashi Yamamoto, Minoru Horie
    Circulation Journal 73 2364 2009年12月
  • 家族性ペースメーカー植え込み症例における遺伝的背景の検討―心臓Na+チャネル病、LaminA/C遺伝子関連心筋症―
    心電図 30(2) 200-220 2010年
  • Long-term prognosis of probands with brugada-pattern ST-elevation in leads V 1-V 3
    Shiro Kamakura, Tohru Ohe, Kiyoshi Nakazawa, Yoshifusa Aizawa, Akihiko Shimizu, Minoru Horie, Satoshi Ogawa, Ken Okumura, Kazufumi Tsuchihashi, Kaoru Sugi, Naomasa Makita, Nobuhisa Hagiwara, Hiroshi Inoue, Hirotsugu Atarashi, Naohiko Aihara, Wataru Shimizu, Takashi Kurita, Kazuhiro Suyama, Takashi Noda, Kazuhiro Satomi, Hideo Okamura, Hitonobu Tomoike
    Circulation: Arrhythmia and Electrophysiology 2 495-503 2009年10月
    Background-The prognosis of patients with saddleback or noncoved type (non-type 1) ST-elevation in Brugada syndrome is unknown. The purpose of this study was to clarify the long-term prognosis of probands with non-type 1 ECG and those with coved (type 1) Brugada-pattern ECG. Methods and Results-A total of 330 (123 symptomatic, 207 asymptomatic) probands with a coved or saddleback ST-elevation ≥1 mm in leads V 1 -V 3 were divided into 2 ECG groups-type 1 (245 probands) and non-type 1 (85 probands)-and were prospectively followed for 48.7≥15.0 months. The absence of type 1 ECG was confirmed by drug provocation test and multiple recordings. The ratio of individuals with a family history of sudden cardiac death (14%) was lower than previous studies. Clinical profiles and outcomes were not notably different between the 2 groups (annual arrhythmic event rate of probands with ventricular fibrillation; type 1: 10.2%, non-type 1: 10.6%, probands with syncope; type 1: 0.6%, non-type 1: 1.2%, and asymptomatic probands; type 1: 0.5%, non-type 1: 0%). Family history of sudden cardiac death at age < 45 years and coexistence of inferolateral early repolarization with Brugada-pattern ECG were independent predictors of fatal arrhythmic events (hazard ratio, 3.28; 95% confidence interval, 1.42 to 7.60; P=0.005; hazard ratio, 2.66; 95% confidence interval, 1.06 to 6.71; P=0.03, respectively, by multivariate analysis), although spontaneous type 1 ECG and ventricular fibrillation inducibility by electrophysiological study were not reliable parameters. Conclusions-The long-term prognosis of probands in non-type 1 group was similar to that of type 1 group. Family history of sudden cardiac death and the presence of early repolarization were predictors of poor outcome in this study, which included only probands with Brugada-pattern ST-elevation. (Circ Arrhythmia Electrophysiol. 2009;2:495-503.) Copyright © 2009 American Heart Association, Inc.
  • ペースメーカ植込み同胞例に認められたあらたなLamin A/C変異A novel lamin A/C gene mutation in siblings treated with cardiac pacemaker.
    心電図 31(1) 18-24 2010年
  • Prevalence of atrial fibrillation in the general population of Japan: An analysis based on periodic health examination
    Hiroshi Inoue, Akira Fujiki, Hideki Origasa, Satoshi Ogawa, Ken Okumura, Isao Kubota, Yoshifusa Aizawa, Takeshi Yamashita, Hirotsugu Atarashi, Minoru Horie, Tohru Ohe, Yoshinori Doi, Akihiko Shimizu, Akiko Chishaki, Tetsunori Saikawa, Katsusuke Yano, Akira Kitabatake, Hideo Mitamura, Itsuo Kodama, Shiro Kamakura
    International Journal of Cardiology 137 102-107 2009年10月
    Background: The mortality and morbidity rates of various cardiovascular diseases differ between Western countries and Japan. The age- and gender-specific prevalence rate of atrial fibrillation (AF) in the general population of Japan was determined using the data from periodic health examinations in 2003. Methods: Data of 630,138 subjects aged 40 years or more (47% were men and 34% were employees of companies and local governments) were collected from northern to southern Japan. The prevalence of diagnosed AF in each 10-year age group of both men and women was determined. Based on these prevalence rates and the Registry of Residents, the number of people having AF in Japan was estimated. Results: The prevalence rate of AF increased as both male and female subjects aged, and it was 4.4% for men but only 2.2% for women aged 80 years or more (p < 0.0001). As a whole, the AF prevalence of men was three times that of women (1.35 versus 0.43%, p < 0.0001). There may be approximately 716,000 people (95% confidence interval (CI), 711,000-720,000) with AF in Japan, an overall prevalence of 0.56%. The number of people having AF was projected to be 1.034 (95% CI, 1.029-1.039) million, an overall prevalence of 1.09%, in 2050. Conclusions: The prevalence of AF increased in Japan as the population aged, as in Western countries. The overall prevalence of AF in Japan is approximately two-thirds of that in the USA. The projected increase in the number of people having AF is modest in Japan in 2050. © 2008 Elsevier Ireland Ltd. All rights reserved.
  • 学会レポート 第27回日本心電学会学術集会
    心電図 30 432-439 2010年
  • Left ventricular involvement in arrhythmogenic right ventricular cardiomyopathy demonstrated by multidetector-row computed tomography.
    Shinro Matsuo, Yuichi Sato, Ichiro Nakae, Daisuke Masuda, Makiko Yomota, Takashi Ashihara, Minoru Horie
    Int J Cardiol  115(3) e129-131 2007年02月
    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a condition in which the right ventricle is partially or totally replaced by the adipose tissue. Pathological abnormalities affect the left ventricle as well as the right ventricle, particularly the epimyocardium. Multidetector-row computed tomography, which allowed excellent visualization of not only the coronary arteries but also the myocardium with submillimeter spatial resolution and high signal-to-noise ratio, would be more suitable for the assessment of the extent of adipose tissue involvement in the right and left ventricular myocardium. We present a patient who was diagnosed as having ARVC with left ventricular involvement and underwent cardioverter defibrillator implantation. © 2006 Elsevier Ireland Ltd. All rights reserved.
  • Cardioverter defibrillator implantation in a patient with double chambered right ventricle.
    Shinro Matsuo, Yuichi Sato, Ichiro Nakae, Yuko Oka, Minoru Horie
    Int J Cardiovasc Imaging 23(4) 459-462 2007年08月
    Double-chambered right ventricle (DCRV) is a rare form of congenital heart disease in which the right ventricle is divided into a high-pressure inlet site and a low-pressure outlet site by anomalous muscle bands. We describe a patient with DCRV presenting with ventricular tachycardia. © Springer Science+Business Media, Inc. 2006.
  • Depiction of a new pulmonary vein variant using multidetector-row computed tomography.
    Shinro Matsuo, Yuichi Sato, Ichiro Nakae, Daisuke Masuda, Tetsuya Matsumoto, Minoru Horie
    Cardiovasc Revasc Med 8(3) 207-208 2007年07月
  • Cholesteryl Ester Transfer Protein, Coronary Calcium, and Intima-Media Thickness of the Carotid Artery in Middle-Age Japanese Men
    Tomonori Okamura, Tomonori Okamura, Akira Sekikawa, Takashi Kadowaki, Aiman El-Saed, Robert D. Abbott, J. David Curb, Daniel Edmundowicz, Yasuyuki Nakamura, Kiyoshi Murata, Atsunori Kashiwagi, Kim Sutton-Tyrrell, Rhobert W. Evans, Joseph M. Zmuda, Hiroshi Maegawa, Atsushi Hozawa, Ken Ichi Mitsunami, Yoshihiko Nishio, Iva Miljkovic-Gacic, Minoru Horie, Naomi Miyamatsu, Yoshitaka Murakami, Lewis H. Kuller, Hirotsugu Ueshima
    American Journal of Cardiology 104 818-822 2009年09月
    The relation between cholesteryl ester transfer protein (CETP) levels and atherosclerosis is controversial. We examined whether the serum CETP levels were associated with subclinical atherosclerosis, independent of its most common gene variant, in a sample of Japanese men. A population-based cross-sectional study of 250 Japanese men aged 40 to 49 years was conducted to assess the intima-media thickness of the carotid artery, coronary artery calcium, serum CETP levels, and the CETP D442G gene variant. Compared with the lowest CETP quartile, the multivariate adjusted odds ratio for coronary artery calcium was 0.77 (95% confidence i nterval 0.18 to 3.36), 0.96 (95% confidence interval 0.27 to 3.40), and 3.49 (95% confidence interval 1.05 to 11.6) with increasing CETP quartiles. The serum CETP quartiles were also positively associated with the intima-media thickness of the carotid artery (adjusted mean 602, 616, 615, and 646 μm for the lowest to top quartile, respectively). The findings remained unchanged after additional adjustment for the CETP D442G gene variant. No significant difference was found in the prevalence of coronary artery calcium or in the mean intima-media thickness of the carotid artery between participants with and without the CETP D442G gene variant. © 2009 Elsevier Inc. All rights reserved.
  • A novel clinical indicator using Tc-99m sestamibi for evaluating cardiac mitochondrial function in patients with cardiomyopathies.
    Shinro Matsuo, Ichiro Nakae, Takayoshi Tsutamoto, Noriake Okamoto, Minoru Horie
    J Am Coll Cardiol 49(9) 61A-62A-220 2007年04月
    Background: Technetium 99m sestamibi (MIBI) is a technetium-labeled myocardial perfusion agent that is taken up by the myocardial cell in proportion to myocardial regional blood flow and remains fixed in the myocardial cell over a long period of time. Previous studies have suggested that MIBI shows very slow myocardial clearance after its initial uptake in an animal model, which is related to mitochondrial function. This study was designed to test the hypothesis that MIBI washout can be used to evaluate the severity of congestive heart failure in comparison to other clinical parameters in patients with cardiomyopathies. Methods and Results: After administration of MIBI, 61 patients with nonischemic congestive heart failure (49 with dilated cardiomyopathy and 12 with other cardiomyopathies) and 7 normal control subjects were examined by electrocardiography-gated myocardial perfusion single photon emission computed tomography and planar data acquisition in the early and delayed phases (interval of 3 hours). Myocardial MIBI washout rates were calculated from the early and delayed planar images. Left ventricular function (systolic and diastolic) was analyzed by use of QGS data. Plasma levels of B-type natriuretic peptide and iodine 123 metaiodobenzylguanidine (MIBG) parameters were also measured. Patients were followed up for a mean of 12 months (range, 1-19 months). As the severity of the New York Heart Association (NYHA) functional class advanced, the washout rate of MIBI increased (21.6% ± 2.4% in those with NYHA class I [n = 23], 28% ± 4% in those with NYHA class II [n = 27] , and 35% ± 5% in those with NYHA class III [n = 10]; P < .05, analysis of variance). The washout rate of MIBI was positively correlated with the level of B-type natriuretic peptide (r = 0.31, P < .05), end-diastolic volume (r = 0.396, P < .01), and end-systolic volume (r = 0.496, P < .01) and was negatively correlated with left ventricular ejection fraction (r = 0.523, P < .01), peak filling rate (r = 0.444, P < .01), and first-third ejection fraction (r = 0.414, P < .01). The parameters of MIBG scintigraphy were calculated as the heart-mediastinum count ratio (1.9 ± 3) and washout rate (38% ± 4%). We found a significant relationship between the washout rate of MIBI and the heart-mediastinum count ratio of MIBG (r = 0.51, P < .01). Patients with a higher washout rate of MIBI had a higher cardiac event rate (≥28%) than those with a lower washout rate ( < 28%) (P < .05). Conclusions: The myocardial washout rate of MIBI is thought to be a novel marker for the diagnosis of myocardial damage or dysfunction, providing prognostic information in patients with congestive heart failure. © 2007 American Society of Nuclear Cardiology.
  • Angiotensin II type 1 receptor mediates partially hyposmotic-induced increase of i Ks current in guinea pig atrium
    Dimitar P. Zankov, Futoshi Toyoda, Mariko Omatsu-Kanbe, Hiroshi Matsuura, Minoru Horie
    Pflugers Archiv European Journal of Physiology 458 837-849 2009年09月
    A repolarizing conduction in the heart augmented by hyposmotic or mechanically induced membrane stretch is the slow component of delayed rectifier K + current (I Ks ). I Ks upregulation is recognized as a factor promoting appearance of atrial fibrillation (AF) since gain-of-function mutations of the channel genes have been detected in congenital AF. Mechanical stretch activates angiotensin II type 1 (AT 1 ) receptor in the absence of its physiological ligand angiotensin II. We investigated the functional role of AT 1 receptor in I Ks enhancement in hyposmotically challenged guinea pig atrial myocytes using the whole-cell patch-clamp method. In atrial myocytes exposed to hyposmotic solution with osmolality decreased to 70% of the physiological level, I Ks was enhanced by 84.1%, the duration of action potential at 90% repolarization (APD 90 ) was decreased by 16.8%, and resting membrane potential was depolarized (+4.9 mV). The hyposmotic-induced effects on I Ks and APD 90 were significantly attenuated by specific AT 1 receptor antagonist candesartan (1 and 5∈μM). Pretreatment of atrial myocytes with protein tyrosine kinase inhibitors tyrphostin A23 and A25 suppressed but the presence of tyrosine phosphatase inhibitor orthovanadate augmented hyposmotic stimulation of I Ks . The above results implicate AT 1 receptor and tyrosine kinases in the hyposmotic modulation of atrial I Ks and suggest acute antiarrhythmic properties of AT 1 antagonists in the settings of stretch-related atrial tachyarrhythmias. © 2009 Springer-Verlag.
  • A novel KCNH2 mutation as a modifier for short QT interval
    Hideki Itoh, Tomoko Sakaguchi, Takashi Ashihara, Wei Guang Ding, Iori Nagaoka, Yuko Oka, Yuko Nakazawa, Takenori Yao, Hikari Jo, Makoto Ito, Kazufumi Nakamura, Tohru Ohe, Hiroshi Matsuura, Minoru Horie
    International Journal of Cardiology 137 83-85 2009年09月
    In a 34-year-old man showing short QT interval (QTc 329 ms), we identified a novel C-terminal KCNH2 mutation, R1135H. Using a heterologous expression system with CHO cells, the mutant channels were found to display a significantly slow deactivation, which resulted in a gain-of-function for reconstituted 'I Kr ' channels. This mutation could modify clinical phenotypes for this patient. © 2008 Elsevier Ireland Ltd. All rights reserved.
  • QT延長の潜在的危険性の予知 : 遺伝子多型:KCNE1-D85N(4.バイオマーカー・遺伝子多型とリスク評価,<特集>第73回日本循環器学会学術集会)
    西尾 由貴子, 堀江 稔
    循環器専門医 : 日本循環器学会専門医誌 17(2) 237-242 2009年09月
  • Coronary risk factor profile and prognostic factors for young Japanese patients undergoing coronary revascularization
    Yutaka Furukawa, Yutaka Furukawa, Natsuhiko Ehara, Ryoji Taniguchi, Yoshisumi Haruna, Neiko Ozasa, Naritatsu Saito, Takahiro Doi, Kozo Hoshino, Toshihiro Tamura, Satoshi Shizuta, Mitsuru Abe, Masanao Toma, Takeshi Morimoto, Takeshi Morimoto, Satoshi Teramukai, Satoshi Teramukai, Masanori Fukushima, Masanori Fukushima, Toru Kita, Takeshi Kimura, Takeshi Kimura, Jong Dae Lee, Kuniyoshi Tanaka, Katsuo Okazaki, Masaaki Takahashi, Teiji Oda, Shigeo Matsui, Naohiro Ohashi, Eiichi Matsuyama, Makoto Kadoya, Yoshiki Takatsu, Shinichi Nomoto, Kazuaki Kataoka, Hajime Kotoura, Masaki Aota, Akira Miura, Satoru Suwa, Chuwa Tei, Ryuzo Sakata, Shuichi Hamasaki, Hiroyuki Yamamoto, Takeshi Aoyama, Takahiro Sakurai, Mitsuo Matsuda, Masahiko Onoe, Yuzo Takeuchi, Ryuji Nohara, Kimisato Nakano, Shigefumi Morioka, Yukikatsu Okada, Kenichi Shiratori, Yasuki Kihara, Michihiro Nasu, Masakiyo Nobuyoshi, Hitoshi Okabayashi, Hitoshi Yasumoto, Jyota Nakano, Tomoyuki Murakami, Katsuya Ishida, Hisao Ogawa, Michio Kawasuji, Seigo Sugiyama, Shoichiro Hagiwara, Kazuaki Mitsudo, Tatsuhiko Komiya, Kazushige Kadota, Masashi Komeda, Ryozo Tatami, Teruaki Ushijima, Akira Yoshida, Hiroyuki Nakajima, Shinji Miki, Ryuichi Hattori, Noboru Nishiwaki, Manabu Shirotani, Hiroshi Kato, Hiroshi Eizawa, Masaru Tanaka, Kazuaki Minami, Minoru Horie, Tohru Asai, Hiroyuki Takashima, Ryuji Higashita, Mamoru Takahashi, Takafumi Tahata, Yoshiki Matoba, Kiyosbi Doyama, Makoto Araki, Akinori Takizawa, Mitsuomi Shimamoto, Fumio Yamazaki, Osamu Doi, Hirofumi Kambara, Katsuhiko Matsuda, Satoshi Kaburagi, Masafumi Nara, Masaki Kawanami, Takashi Konishi, Yoshihisa Nakagawa
    Circulation Journal 73 1459-1465 2009年08月
    Background: The prevalence of coronary artery disease (CAD) is increasing in young adults. Risk factor profiling will help to prevent heart attacks in young patients. This study aimed to analyze the risk factor profile and predictors of major cardiovascular events (MACE) in young CAD patients. Methods and Results: From the Coronary REvascularization Demonstrating Outcome study in the Kyoto (CREDO-Kyoto) registry of Japanese patients undergoing their first coronary revascularization, 6,320 patients with complete data for all variables for statistical analyses were divided into younger (≤55 years; n=898; 14.3%) and older ( > 55 years; n=5,422; 85.7%) patients. The risk factors that were more prevalent in the younger patients than in the older patients included: male sex, body mass index of > 25kg/m 2 , current smoker, family history of CAD, dyslipidemia and metabolic syndrome-like risk factor accumulation. Multivariate analyses revealed that chronic kidney disease (CKD) was the only significant predictor of MACE, the composite of cardiovascular death, myocardial infarction and cerebrovascular accident, in the younger patients. Importance of CKD as a prognostic factor was consistently shown by a multivariate analysis in the older patients. Conclusions: Accumulation of multiple risk factors is prevalent and CKD is associated with MACE in young Japanese CAD patients.
  • 心臓交感神経指標としての(冠状静脈洞-大動脈幹)ノルエピネフリン濃度較差(4.バイオマーカー・遺伝子多型とリスク評価,<特集>第73回日本循環器学会学術集会)
    蔦本 尚慶, 西山 敬三, 山路 正之, 河原 千穂, 山本 孝, 藤井 応理, 堀江 稔
    循環器専門医 : 日本循環器学会専門医誌 17(2) 243-249 2009年09月
  • Effect of carvedilol on plasma adiponectin concentration in patients with chronic heart failure
    Masayuki Yamaji, Takayoshi Tsutamoto, Toshinari Tanaka, Chiho Kawahara, Keizo Nishiyama, Takashi Yamamoto, Masanori Fujii, Minoru Horie
    Circulation Journal 73 1067-1073 2009年06月
    Background: Patients with a high plasma adiponectin have a poor prognosis in chronic heart failure (CHF). Angiotensin-Converting enzyme inhibitors and angiotensin II receptor blockers are reported to increase the plasma adiponectin concentration, but the effect of β-blockers on plasma adiponectin in patients with CHF remains unknown. Methods and Results: Blood samples were collected at before and 6 months after administration of carvedilol in 44 CHF patients. The hemodynamic parameters, echocardiography, plasma concentrations of brain natriuretic peptide (BNP), norepinephrine and adiponectin were measured. Six months after treatment, there were significantly decreased plasma concentrations of adiponectin (15.8±1.4 to 11.0±1.1μg/ml, P < 0.0001), BNP and norepinephrine and increased left ventricular ejection fraction (LVEF). On stepwise multivariable analyses, a higher plasma adiponectin concentration before treatment (rs=-0.561, P < 0.0001) was a significant independent predictor of a greater decrease in adiponectin concentration and the decrease in plasma adiponectin concentration was significantly correlated with the improvement of LVEF (r=-0.561, P < 0.0001). Conclusions: These findings indicate that carvedilol decreases plasma adiponectin concentration and that the decrease in plasma adiponectin is associated with the improvement of LVEF after treatment with carvedilol in CHF patients.
  • Novel KCNE3 mutation reduces repolarizing potassium current and associated with long QT syndrome
    Seiko Ohno, Futoshi Toyoda, Dimitar P. Zankov, Dimitar P. Zankov, Hidetada Yoshida, Takeru Makiyama, Keiko Tsuji, Toshihiro Honda, Kazuhiko Obayashi, Hisao Ueyama, Wataru Shimizu, Yoshihiro Miyamoto, Shiro Kamakura, Hiroshi Matsuura, Toru Kita, Minoru Horie, Minoru Horie
    Human Mutation 30 557-563 2009年04月
    Long QT syndrome(LQTS) is an inherited disease involving mutations in the genes encoding a number of cardiac ion channels and a membrane adaptor protein. Among the genes that are responsible for LQTS, KCNE1 and KCNE2 are members of the KCNE family of genes, and function as ancillary subunits of Kv channels. The third KCNE gene, KCNE3, is expressed in cardiac myocytes and interacts with KCNQ1 to change the channel properties. However, KCNE3 has never been linked to LQTS. To investigate the association between KCNE3 and LQTS, we conducted a genetic screening of KCNE3 mutations and single nucleotide polymorphisms(SNPs) in 485 Japanese LQTS probands using DHPLC- WAVE system and direct sequencing. Consequently, we identified two KCNE3 missense mutations, located in the N- and C-terminal domains. The functional effects of these mutations were examined by heterologous expression systems using CHO cells stably expressing KCNQ1. One mutation, p.R99γH was identified in a 76-year-old woman who suffered torsades de pointes(TdP) after administration of disopyramide. Another mutation, p.T4A was identified in a 16-year-old boy and 67-year-old woman. Although the boy carried another KCNH2 mutation, he was asymptomatic. On the other hand, the woman suffered from hypokalemia-induced TdP. In a series of electrophysiological analyses, the KCNQ1(Q1) +KCNE3(E3)-R99γH channel significantly reduced outward current compared to Q1+E3-WT, though the current density of the Q11E3-T4A channel displayed no statistical significance. This is the first report of KCNE3 mutations associated with LQTS. Screening for variants in the KCNE3 gene is of clinical importance for LQTS patients. © 2009 Wiley-Liss,Inc.
  • 心不全マーカーと心血管リスク予測因子としてのナトリウム利尿ペプチド
    蔦本 尚慶, 堀江 稔
    臨床薬理 = Japanese journal of clinical pharmacology 40(4) 173S-174S 2009年07月
  • Evaluation of channel function after alteration of amino acid residues at the pore center of KCNQ1 channel
    Taruna Ikrar, Taruna Ikrar, Haruo Hanawa, Hiroshi Watanabe, Yoshiyasu Aizawa, Mahmoud M. Ramadan, Masaomi Chinushi, Minoru Horie, Yoshifusa Aizawa
    Biochemical and Biophysical Research Communications 378 589-594 2009年01月
    The effect of the electrical charge or the size of the amino acid residue at the pore center of a slowly activation component of the delayed rectifier potassium channel: KCNQ1 was studied. K + currents were measured after transfection of one of four KCNQ1 mutants: substituting Isoleucine with Lysine, Glutamate, Valine or Glycine and then transfected in COS-7 cells. Both the negatively- and positive charged residue I313 K and I313E showed a loss of function when expressed alone and a dominant negative suppression when co-expressed with wild type KCNQ1. When the site was substituted with the smallest neutral amino acid residue: I313G, there was a small reduction of current when transfected alone and a gain of function when co-transfected with the wild type. I313V showed no difference from the wild type. Changes of amino acid residue at the pore center of KCNQ1 may alter the channel function but this depends on the electrical charge or the size of amino acid residue. © 2008 Elsevier Inc. All rights reserved.
  • Inhibitory actions of the phosphatidylinositol 3-kinase inhibitor LY294002 on the human Kv1.5 channelPAPER
    J. Wu, J. Wu, J. Wu, W. G. Ding, H. Matsuura, H. Matsuura, K. Tsuji, W. J. Zang, M. Horie
    British Journal of Pharmacology 156 377-387 2009年01月
    Background and purpose: Kv1.5 channels conduct the ultra-rapid delayed rectifier potassium current (I Kur ), and in humans, Kv1.5 channels are highly expressed in cardiac atria but are scarce in ventricles. Pharmacological blockade of human Kv1.5 (hKv1.5) has been regarded as effective for prevention and treatment of re-entry-based atrial tachyarrhythmias. Here we examined blockade of hKv1.5 channels by LY294002, a well-known inhibitor of phosphatidylinositol 3-kinase (PI3K). Experimental approach: hKv1.5 channels were heterologously expressed in Chinese hamster ovary cells. Effects of LY294002 on wild-type and mutant (T462C, H463C, T480A, R487V, A501V, I502A, I508A, L510A and V516A) hKv1.5 channels were examined by using the whole-cell patch-clamp method. Key results: LY294002 rapidly and reversibly inhibited hKv1.5 current in a concentration-dependent manner (IC 50 of 7.9 ̄mol·L -1 ). In contrast, wortmannin, a structurally distinct inhibitor of PI3K, had little inhibitory effect on hKv1.5 current. LY294002 block of hKv1.5 current developed with time during depolarizing voltage-clamp steps, and this blockade was also voltage-dependent with a steep increase over the voltage range for channel openings. The apparent binding (k +1 ) and unbinding (k -1 ) rate constants were calculated to be 1.6 ̄mol·L -1-1 ·s -1 and 5.7 s -1 respectively. Inhibition by LY294002 was significantly reduced in several hKv1.5 mutant channels: T480A, R487V, I502A, I508A, L510A and V516A. Conclusions and implications: LY294002 acts directly on hKv1.5 currents as an open channel blocker, independently of its effects on PI3K activity. Amino acid residues located in the pore region (Thr480, Arg487) and the S6 segment (Ile502, Ile508, Leu510, Val516) appear to constitute potential binding sites for LY294002. Mandarin translation of abstract. © 2009 The British Pharmacological Society.
  • QT延長症候群 (特集 小児疾患における臨床遺伝学の進歩) -- (話題の疾患遺伝子)
    堀江 稔
    小児科 50(7) 1083-1087 2009年06月
  • アップストリーム治療 (特集 心房細動) -- (心房細動の治療)
    堀江 稔
    診断と治療 97(5) 1022-1027 2009年05月
  • 薬剤性QT延長症候群 (特集 危険な不整脈の予防と治療)
    堀江 稔
    ICUとCCU 33(1) 19-24 2009年01月
  • Cinnamyl-3,4-dihydroxy-α-cyanocinnamate and nordihydroguaiaretic acid inhibit human Kv1.5 currents independently of lipoxygenase
    Ying Zi Gong, Ying Zi Gong, Ying Zi Gong, Wei Guang Ding, Jie Wu, Keiko Tsuji, Minoru Horie, Hiroshi Matsuura
    European Journal of Pharmacology 600 18-25 2008年12月
    In humans, Kv1.5 (hKv1.5) channels conduct the ultra-rapid delayed rectifier K + current (I Kur ) that is important for the repolarization of cardiac action potentials. We aimed at examining the effect of lipoxygenase inhibitors cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC), nordihydroguaiaretic acid (NDGA), and gossypol on hKv1.5 wild-type and mutant channels heterologously expressed in Chinese hamster ovary (CHO) cells, by use of the site-directed mutagenesis and whole-cell patch-clamp method. CDC and NDGA, but not gossypol, a structurally dissimilar inhibitor, reversibly inhibited hKv1.5 current in a concentration-dependent manner with IC 50 of 5.7 μM and 16.4 μM, respectively. The blockade evoked by both drugs was voltage-dependent between - 20 and + 10 mV (voltage range of channel opening). Moreover, this blocking action was found to progress with time during depolarizing voltage steps with a more rapid block at higher concentrations. CDC induced slight but significant delay of the deactivation rate. However, NDGA markedly slowed the deactivation time course, resulting in a tail crossover phenomenon. The recovery time constants from current block at repolarizing potentials for CDC and NDGA were 60.9 ms and 129.7 ms, respectively. Mutation of arginine 487 to valine (R487V) in the outer pore region of the channel significantly reduced the CDC action. These results demonstrate for the first time that CDC and NDGA block hKv1.5 channels by binding to the open state of the channels, independently of their effects on lipoxygenase activity. The putative binding site for CDC appears to be related to arginine 487 located in the outer pore region. © 2008 Elsevier B.V. All rights reserved.
  • QT延長症候群
    小児科 50(7) 1083-1087 2009年
  • Better survival with statin administration after revascularization therapy in Japanese patients with coronary artery disease - Perspectives from the CREDO-Kyoto Registry
    Yutaka Furukawa, Yutaka Furukawa, Yutaka Furukawa, Ryoji Taniguchi, Natsuhiko Ehara, Neiko Ozasa, Yoshisumi Haruna, Naritatsu Saito, Takahiro Doi, Kozo Hoshino, Satoshi Shizuta, Takeshi Morimoto, Takeshi Morimoto, Yukiko Imai, Satoshi Teramukai, Satoshi Teramukai, Masanori Fukushima, Masanori Fukushima, Toru Kita, Takeshi Kimura, Takeshi Kimura, Jong Dae Lee, Kuniyoshi Tanaka, Katsuo Okazaki, Masaaki Takahashi, Teiji Oda, Shigeo Matsui, Naohiro Ohashi, Eiichi Matsuyama, Makoto Kadoya, Yoshiki Takatsu, Shinichi Nomoto, Kazuaki Kataoka, Hajime Kotoura, Masaki Aota, Akira Miura, Satoru Suwa, Chuwa Tei, Ryuzo Sakata, Shuichi Hamasaki, Hiroyuki Yamamoto, Takeshi Aoyama, Takahiro Sakurai, Mitsuo Matsuda, Masahiko Onoe, Yuzo Takeuchi, Ryuji Nohara, Kimisato Nakano, Shigefumi Morioka, Yukikatsu Okada, Kenichi Shiratori, Yasuki Kihara, Michihiro Nasu, Masakiyo Nobuyoshi, Hitoshi Okabayashi, Hitoshi Yasumoto, Jyota Nakano, Tomoyuki Murakami, Katsuya Ishida, Hisao Ogawa, Michio Kawasuji, Seigo Sugiyama, Shoichiro Hagiwara, Kazuaki Mitsudo, Tatsuhiko Komiya, Kazushige Kadota, Masashi Komeda, Ryozo Tatami, Teruaki Ushijima, Akira Yoshida, Hiroyuki Nakajima, Shinji Miki, Ryuichi Hattori, Noboru Nishiwaki, Manabu Shirotani, Hiroshi Kato, Hiroshi Eizawa, Masaru Tanaka, Kazuaki Minami, Minoru Horie, Tohru Asai, Hiroyuki Takashima, Ryuji Higashita, Mamoru Takahashi, Takafumi Tahata, Yoshiki Matoba, Kiyoshi Doyama, Makoto Araki, Akinori Takizawa, Mitsuomi Shimamoto, Fumio Yamazaki, Osamu Doi, Hirofumi Kambara, Katsuhiko Matsuda, Satoshi Kaburagi, Masafumi Nara, Masaki Kawanami, Takashi Konishi, Kazunobu Nishimura, Seiji Ootani
    Circulation Journal 72 1937-1945 2008年12月
    Background: The importance of statins in cardiovascular prevention has been demonstrated in various patient subsets. This study aimed to evaluate the effects of statins on long-term outcomes of Japanese patients undergoing their first coronary revascularization. Methods and Results: A total of 9,225 patients undergoing their first coronary revascularizations during 2000-2002 were divided into 2 groups according to the use of statins at discharge; patients with acute myocardial infarction were not included. Statins was administered to only 28.5% (n=2,630) of the patients. The median follow-up period was 3.5 years. Patients on statin therapy showed lower all-cause (5.2% vs 10.0%; p < 0.0001) and cardiovascular (3.2% vs 6.2%; p < 0.0001) mortality than those without statins (n=6,595) by Kaplan-Meier analysis and log-rank test. After adjustment by multivariate analysis according to 29 variables, statin therapy remained as an independent predictor of reduced all-cause (relative risk ratio (RR) 0.71, 95% confidence interval (CI) 0.59-0.86, p=0.0005) and cardiovascular (RR 0.72, 95% CI 0.56-0.91, p=0.0067) mortality. The validity of RR of statin therapy in multivariate analysis was further confirmed by risk adjustment using propensity scores (all-cause mortality: propensity-adjusted RR 0.70, 95% CI 0.58-0.85, p=0.0003; cardiovascular mortality: propensity-adjusted RR 0.70, 95% CI 0.54-0.89, p=0.0038). Conclusions: Statin therapy started at hospital discharge was associated with increased chance of survival in Japanese patients undergoing their first coronary revascularization.
  • Transcardiac increase in norepinephrine and prognosis in patients with chronic heart failure
    Takayoshi Tsutamoto, Keizo Nishiyama, Hiroshi Sakai, Toshinari Tanaka, Masanori Fujii, Takashi Yamamoto, Masayuki Yamaji, Minoru Horie
    European Journal of Heart Failure 10 1208-1214 2008年12月
    Background: No previous study has compared the transcardiac gradient of norepinephrine (NE) and the prognosis of patients with chronic heart failure (CHF). Aim: To evaluate the prognostic role of the transcardiac gradient of NE in patients with CHF. Methods: We measured haemodynamic parameters and plasma levels of NE, brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in the aortic root (AO) and coronary sinus (CS) in 356 consecutive patients with CHF. Results: During a median follow-up of 3.5 years, 40 patients died. Transcardiac gradients of BNP (273 ± 276 vs. 472 ± 433 pg/mL, p < 0.0001), NT-proBNP (417 ± 700 vs. 928 ± 1093 pg/mL, p < 0.0001) and NE (114 ± 160 vs. 473 ± 992 pg/mL, p < 0.0001) were significantly higher in non-survivors than survivors. After adjustment for clinical variables associated with CHF including haemodynamics and neurohumoral factors, the transcardiac gradient of NE (p < 0.0001) and plasma log NT-proBNP (p < 0.0001) were independent prognostic predictors. Among 67 patients in whom 123 I-metaiodobenzylguanidine (MIBG) could be performed, transcardiac increase in NE was correlated with the washout rate (r = 0.398, p = 0.0009) and was a superior predictor of mortality than MIBG parameters on stepwise multivariable Cox proportional hazards regression analyses. Conclusion: The transcardiac increase in NE is an independent and useful prognostic predictor for evaluating the prognosis of CHF patients. © 2008 European Society of Cardiology.
  • 第13回 : 日本心電学会学術奨励賞
    堀江 稔
    心電図 = Electrocardiology 28(6) 2008年12月
  • Constrictive pericarditis as an emerging manifestation of hyper-IgG4 disease
    Toshiro Sugimoto, Yoshikata Morita, Keiji Isshiki, Takashi Yamamoto, Takashi Uzu, Atsunori Kashiwagi, Minoru Horie, Tohru Asai
    International Journal of Cardiology 130 2008年11月
    A 68-year-old Japanese man was admitted for evaluation of right pleural effusion and bilateral leg edema that had progressively worsened over 6 months. As chest computed tomography revealed marked pericardial thickening, we performed a pericardiectomy, resulting in the remarkable improvement of his clinical manifestations. However, pleural fibrosis associated with fever of unknown origin soon developed. An elevated serum level of serum IgG4 and infiltration of IgG4-positive plasma cell in the resected pericardium were identified; thus, our patient might have hyper-IgG4 disease. Our case is the first report describing constrictive pericarditis as an initial manifestation of hyper-IgG4 disease. © 2007 Elsevier Ireland Ltd. All rights reserved.
  • The factors contributing to whether or not hypertensive patients bring their home blood pressure record to the outpatient clinic
    Shinji Tamaki, Yasuyuki Nakamura, Masanori Teramura, Hiroshi Sakai, Tomoyuki Takayama, Tabito Okabayashi, Takeshi Kawashima, Minoru Horie
    Internal Medicine 47 1561-1565 2008年11月
    Objective. We investigated the factors contributing to whether or not hypertensive patients brought their home blood pressure records to the outpatient clinic. Method. We studied 325 hypertensive patients [169 men (66.3±11.4 years old) and 156 women (68.1±11.2 years old)] who had received medical treatment for hypertension in our outpatient clinic from June to August 2006. Results. Of the 325 patients studied, 206 (63.4%, 101 men, 105 women) brought their home blood pressure records to our outpatient clinic. Logistic analysis showed age [odds ratio (OR) =0.95; 95% confidence interval (CI): 0.93-0.98; p=0.0002] , systolic blood pressure in outpatient clinic (OR=1.02; 95% CI: 1.00-1.04; p=0.0488) and the number of medicines prescribed (OR=1.94; 95% CI: 1.37-2.75; p=0.0002) were independent factors contributing to whether or not hypertensive patients bring along their home blood pressure records to the outpatient clinic. Conclusion. The contributing factors determining whether the patients bring their home blood pressure records to the outpatient clinic were: younger age, higher systolic blood pressure in the outpatient clinic, and a higher number of antihypertensive drugs. In conclusion, our results suggest that physicians should further motivate older patients, with well-controlled blood pressure in the outpatient clinic, to bring their home blood pressure records to the outpatient clinic. © 2008 The Japanese Society of Internal Medicine.
  • ペースメーカ、ICD、CRTを受けた患者の社会復帰・就学・就労に関するガイドライン
    奥村 謙, 安部 治彦, 小川 聡, 笠貫 宏, 鎌倉 史郎, 住友 直方, 新田 隆, 野島 俊雄, 堀江 正知, 松崎 益徳, 山口 巖, 江島 浩一郎, 金丸 浩, 菅野 重人, 佐々木 真吾, 豊島 健, 中島 博, 長友 敏寿, 野田 崇, 副島 京子, 村田 和也, 渡辺 重行, 大江 透, 加藤 貴雄, 田邉 晃久, 土肥 誠太郎, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 72 1133-1192 2008年11月
  • 血管炎症候群の診療ガイドライン
    尾崎 承一, 安藤 太三, 居石 克夫, 磯部 光章, 太田 敬, 小林 茂人, 重松 宏, 種本 和雄, 中島 康雄, 中林 公正, 能勢 眞人, 松永 尚文, 宮田 哲郎, 由谷 親夫, 吉田 雅治, 吉田 晃敏, 有村 義宏, 石津 明洋, 岩井 武尚, 岡崎 貴裕, 岡田 宗正, 片岡 浩, 金子 一成, 川名 誠司, 木田 一成, 小林 泰之, 古森 公浩, 坂本 一郎, 椎谷 紀彦, 重松 邦広, 高橋 淳士, 滝澤 始, 長岡 泰司, 長澤 浩平, 野島 美久, 橋本 博史, 濱口 真吾, 廣村 桂樹, 深谷 修作, 正木 久男, 松本 常男, 山田 秀裕, 吉田 俊治, 熊谷 俊一, 小池 隆夫, 笹嶋 唯博, 福井 次矢, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 72 1253-1346 2008年11月
  • ペースメーカ、ICD、CRTを受けた患者の社会復帰・就学・就労に関するガイドライン(循環器病の診断と治療に関するガイドライン(2006-2007年度合同研究班報告))
    奥村 謙, 安部 治彦, 小川 聡, 笠貫 宏, 鎌倉 史郎, 住友 直方, 新田 隆, 野島 俊雄, 堀江 正知, 松崎 益徳, 山口 巖, 江島 浩一郎, 金丸 浩, 菅野 重人, 佐々木 真吾, 豊島 健, 中島 博, 長友 敏寿, 野田 崇, 副島 京子, 村田 和也, 渡辺 重行, 大江 透, 加藤 貴雄, 田邉 晃久, 土肥 誠太郎, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 72(0) 1133-1174 2008年11月
  • ペースメーカ、ICD、CRTを受けた患者の社会復帰・就学・就労に関するガイドライン(ダイジェスト版,循環器病の診断と治療に関するガイドライン(2006-2007年度合同研究班報告))
    奥村 謙, 安部 治彦, 小川 聡, 笠貫 宏, 鎌倉 史郎, 住友 直方, 新田 隆, 野島 俊雄, 堀江 正知, 松崎 益徳, 山口 巖, 江島 浩一郎, 金丸 浩, 菅野 重人, 佐々木 真吾, 豊島 健, 中島 博, 長友 敏寿, 野田 崇, 副島 京子, 村田 和也, 渡辺 重行, 大江 透, 加藤 貴雄, 田邉 晃久, 土肥 誠太郎, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 72(0) 1175-1192 2008年11月
  • 血管炎症候群の診療ガイドライン(循環器病の診断と治療に関するガイドライン(2006-2007年度合同研究班報告))
    尾崎 承一, 安藤 太三, 居石 克夫, 磯部 光章, 太田 敬, 小林 茂人, 重松 宏, 種本 和雄, 中島 康雄, 中林 公正, 能勢 眞人, 松永 尚文, 宮田 哲郎, 由谷 親夫, 吉田 雅治, 吉田 晃敏, 有村 義宏, 石津 明洋, 岩井 武尚, 岡崎 貴裕, 岡田 宗正, 片岡 浩, 金子 一成, 川名 誠司, 木田 一成, 小林 泰之, 古森 公浩, 坂本 一郎, 椎谷 紀彦, 重松 邦広, 高橋 淳士, 滝澤 始, 長岡 泰司, 長澤 浩平, 野島 美久, 橋本 博史, 濱口 真吾, 廣村 桂樹, 深谷 修作, 正木 久男, 松本 常男, 山田 秀裕, 吉田 俊治, 熊谷 俊一, 小池 隆夫, 笹嶋 唯博, 福井 次矢, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 72(0) 1253-1318 2008年11月
  • 血管炎症候群の診療ガイドライン(ダイジェスト版,循環器病の診断と治療に関するガイドライン(2006-2007年度合同研究班報告))
    尾崎 承一, 安藤 太三, 居石 克夫, 磯部 光章, 太田 敬, 小林 茂人, 重松 宏, 種本 和雄, 中島 康雄, 中林 公正, 能勢 眞人, 松永 尚文, 宮田 哲郎, 由谷 親夫, 吉田 雅治, 吉田 晃敏, 有村 義宏, 石津 明洋, 岩井 武尚, 岡崎 貴裕, 岡田 宗正, 片岡 浩, 金子 一成, 川名 誠司, 木田 一成, 小林 泰之, 古森 公浩, 坂本 一郎, 椎谷 紀彦, 重松 邦広, 高橋 淳士, 滝澤 始, 長岡 泰司, 長澤 浩平, 野島 美久, 橋本 博史, 濱口 真吾, 廣村 桂樹, 深谷 修作, 正木 久男, 松本 常男, 山田 秀裕, 吉田 俊治, 熊谷 俊一, 小池 隆夫, 笹嶋 唯博, 福井 次矢, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 72(0) 1319-1346 2008年11月
  • 虚血性心疾患 虚血性心疾患の概念と病態生理 (新時代の糖尿病学(4)病因・診断・治療研究の進歩) -- (糖尿病に起因する合併症 慢性合併症--大血管症)
    堀江 稔
    日本臨床 66(0) 349-353 2008年11月
  • 68) QT延長症候群として経過観察中に心肺停止となった一例(第105回日本循環器学会近畿地方会)
    城日 加里, 福山 恵, 八尾 武憲, 中澤 優子, 伊藤 英樹, 芦原 貴司, 杉本 喜久, 伊藤 誠, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 72(0) 2008年10月
  • Cardiac scintigraphic findings of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes: A case report
    Shinro Matsuo, Kenichi Nakajima, Seigo Knuya, Yuichi Sato, Naoya Matsumoto, Minoru Horie
    Experimental and Clinical Cardiology 13 93-95 2008年06月
    A 49-year-old woman was admitted to hospital because of heart failure. She was diagnosed as having mitochondrial cardiomyopathy and diabetes mellitus. Echocardiography revealed a hypertrophic and poorly contracting left ventricle. A diagnosis of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes was established by muscle biopsy. She underwent technetium-99m-sestamibi ( 99m Tc-MIBI) and beta-methyl-p- 123 I-iodophenyl-pentadecanoic acid ( 123 I-BMIPP) scintigraphic examinations. 99m Tc-MIBI single-photon emission computed tomography revealed reduced tracer uptake in the hypertrophic left ventricular inferior wall. In contrast, there was an increase in 123I -BMIPP uptake in the in the region of reduced 99m Tc-MIBI uptake ( 99m Tc-MIBI/ 123 I-BMIPP mismatch). There was rapid washout of 99m Tc-MIBI from the myocardium (washout rate increased by 30%). Decreased 99m Tc-MIBI and increased 123 I-BMIPP uptake ( 99m Tc-MIBI/ 123 I-BMIPP mismatch) were the characteristics of cardiac involvement in mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. © 2008 Pulsus Group Inc. All rights reserved.
  • 145) 早期血栓閉塞型大動脈解離により心肺停止に至ったと考えられた一症例(第105回日本循環器学会近畿地方会)
    太田 宗樹, 藤井 応理, 堀江 稔, 藤野 和典, 浜本 徹, 佐々木 禎治, 五月女 隆男, 江口 豊
    Circulation journal : official journal of the Japanese Circulation Society 72(0) 2008年10月
  • Beneficial effect of perindopril on cardiac sympathetic nerve activity and brain natriuretic peptide in patients with chronic heart failure - Comparison with enalapril
    Takayoshi Tsutamoto, Takayoshi Tsutamoto, Toshinari Tanaka, Hiroshi Sakai, Keizo Nishiyama, Masanori Fujii, Takashi Yamamoto, Ichiro Nakae, Masato Ohnishi, Atsuyuki Wada, Minoru Horie
    Circulation Journal 72 740-746 2008年05月
    Background: In patients with chronic heart failure (CHF), it remains unclear whether perindopril is more cardioprotective than enalapril. Methods and Results: Forty-five stable CHF outpatients undergoing conventional therapy including enalapril therapy were randomized to 2 groups [group I (n=24): continuous enalapril treatment; group II (n=21): enalapril was changed to perindopril]. Cardiac sympathetic nerve activity was evaluated using cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphy, hemodynamic parameters and neurohumoral factors before and 6 months after treatment. There was no difference in baseline characteristics between the 2 groups. In group I, there were no changes in MIBG parameters, left ventricular ejection fraction (LVEF) or plasma level of brain natriuretic peptide (BNP). In contrast, in group II the delayed heart/mediastinum count ratio was significantly increased (2.0±0.07 vs 2.15±0.07, p=0.013) and the washout rate was significantly decreased (33.0±1.4 vs 30.5±1.2, p=0.030) after 6 months com pared with the baseline value. In addition, LVEF was significantly increased and the plasma BNP level was significantly decreased. Conclusion: These findings suggest that for the treatment of CHF, perindopril is superior to enalapril with respect of cardiac sympathetic nerve activity and BNP.
  • 心房細動は遺伝するのか? (特集 生活習慣病は遺伝するか?--家族性生活習慣病?)
    堀江 稔
    成人病と生活習慣病 38(10) 1180-1182 2008年10月
  • Mutation site dependent variability of cardiac events in Japanese LQT2 form of congenital long-QT syndrome
    Iori Nagaoka, Wataru Shimizu, Hideki Itoh, Satoshi Yamamoto, Tomoko Sakaguchi, Yuko Oka, Keiko Tsuji, Takashi Ashihara, Makoto Ito, Hidetada Yoshida, Seiko Ohno, Takeru Makiyama, Yoshihiro Miyamoto, Takashi Noda, Shiro Kamakura, Masaharu Akao, Minoru Horie, Minoru Horie
    Circulation Journal 72 694-699 2008年05月
    Background: In the LQT2 form of long QT syndrome (LQTS), mutation sites are reported to correlate with clinical phenotypes in Caucasians, but the relationship in Asian patients remains unknown. The present study was designed to determine whether the location of KCNH2 mutations would influence the arrhythmic risk in LQT2 patients. Methods and Results: In 118 genetically-confirmed LQT2 patients (69 families, 62 KCNH2 mutations), the ECG parameters, Schwartz scores, and the incidence of cardiac events, defined as syncope, aborted cardiac arrest, and sudden cardiac death, were evaluated. To examine the effect of mutation sites, the participants were divided accordingly: pore (n=56) and non-pore (n=62) groups. The corrected QTend interval was significantly greater in the pore than in the non-pore group (QTc; 522±63ms vs 490±49 ms, p=0.002). In this study, the clinical course of each of the probands did not differ according to the mutation sites, whereas non-probands carrying the pore site mutation experienced their first cardiac events at significantly younger age than those with the non-pore site mutation (log-rank, p=0.0005). Conclusions: In a Japanese LQT2 cohort, family members with the pore site mutation were at higher arrhythmic risk than those with the non-pore site mutation.
  • 薬剤性QT延長症候群の遺伝子異常と分子病態(2.QT延長のサイエンス,<特集>第72回日本循環器学会学術集会)
    伊藤 英樹, 岡 優子, 堀江 稔
    循環器専門医 : 日本循環器学会専門医誌 16(2) 227-230 2008年09月
  • Effects of a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor, Fluvastatin, on Coronary Spasm After Withdrawal of Calcium-Channel Blockers
    Hirofumi Yasue, Yuji Mizuno, Eisaku Harada, Teruhiko Itoh, Hitoshi Nakagawa, Masafumi Nakayama, Hisao Ogawa, Shinji Tayama, Takasi Honda, Seiji Hokimoto, Shuichi Ohshima, Youichi Hokamura, Kiyotaka Kugiyama, Minoru Horie, Michihiro Yoshimura, Masaki Harada, Shiroh Uemura, Yoshihiko Saito
    Journal of the American College of Cardiology 51 1742-1748 2008年05月
    Objectives: The purpose of this study was to determine whether a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) suppresses coronary spasm. Background: Coronary spasm is associated with endothelial dysfunction. Statins have been shown to improve endothelial function. Methods: This was a prospective, randomized, open-label, end point study. Sixty-four patients wh o had no significant organic coronary stenosis and in whom coronary spasm was induced by intracoronary injection of acetylcholine (ACh) were randomly assigned to fluvastatin 30 mg/day plus the conventional calcium-channel blocker (CCB) therapy (31 patients, statin group) or the conventional CCB therapy (33 patients, nonstatin group). After 6 months of treatment, the intracoronary injection of ACh was repeated and the coronary spasm was assessed. Results: Coronary spasm was suppressed in 16 of the 31 patients (51.5%, p < 0.0001) of the statin group and in 7 of the 33 patients (21.2%, p = 0.0110) of the nonstatin group after 6 months of treatment. Thus, the number of patients with ACh-induced coronary spasm was significantly reduced in the statin group as compared with the nonstatin group (51.6% vs. 21.2%, p = 0.0231) after 6 months of treatment. Conclusions: The addition of fluvastatin 30 mg/day to the conventional CCB therapy for 6 months significantly reduced the number of patients with ACh-induced coronary spasm as compared with the conventional CCB therapy. Thus, a statin (fluvastatin) may possibly be a novel therapeutic drug for coronary spasm. © 2008 American College of Cardiology Foundation.
  • 循環器疾患の遺伝子学 (臨床遺伝子学'08)
    堀江 稔
    最新医学 63(0) 1814-1826 2008年09月
  • Whole-body periodic acceleration enhances brachial endothelial function
    Tetsuya Matsumoto, Tetsuya Matsumoto, Masatoshi Fujita, Yasuhiro Tarutani, Tetsunobu Yamane, Hiroyuki Takashima, Ichiro Nakae, Minoru Horie
    Circulation Journal 72 139-143 2008年03月
    Background: Periodic acceleration in the direction of the spinal axis through repetitive movement increases the shear stress on the vascular endothelium. In the present study it was assessed whether whole-body periodic acceleration with a new device would enhance endothelial function in sedentary adult volunteers. Methods and Results: Twenty-six sedentary subjects (44±3 years) were randomly assigned to remain sedentary or perform exercise training for 4 weeks, followed by crossover. Periodic acceleration was applied with a horizontal motion platform at 2-3 Hz and approximately ±2.2 m/s 2 for 45 min. Increases in the brachial artery diameter were examined at rest, during reactive hyperemia (flow-mediated dilatation: %FMD) and after sublingual administration of 0.3 mg nitroglycerin (%NTG) using high-resolution ultrasound. All subjects completed the study with no adverse side-effects. There were no significant changes in the resting heart rate or arterial pressure, body weight, or lipid profiles during the study. Although %FMD did not change during the non-training period with periodic acceleration, it significantly increased from 7.3±0.4% at baseline to 8.4±0.4% after the training period (p < 0.05), while %NTG remained unchanged. Conclusions: Whole-body periodic acceleration with a horizontal motion platform improved vascular endothelial function in sedentary adults. This device might offer an alternative to active exercise for patients whose medical condition limits physical activity.
  • 69) 早期の心臓再同期療法が有効であったLamin A/C遺伝子関連心筋症の1家系(第104回日本循環器学会近畿地方会)
    牧山 武, 赤尾 昌治, 静田 聡, 土井 孝浩, 大野 聖子, 西尾 由貴子, 西山 慶, 木村 剛, 北 徹, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 72(0) 2008年04月
  • 112) 縦隔手術および縦隔放射線治療後に右心不全が慢性化し,特異な右心圧波形を示した一例(第104回日本循環器学会近畿地方会)
    羽野 嘉文, 山根 哲信, 蔦本 尚慶, 藤井 応理, 高島 弘行, 山本 孝, 松本 祐一, 北川 直孝, 中江 一郎, 伊藤 誠, 堀江 稔, 東 秋弘
    Circulation journal : official journal of the Japanese Circulation Society 72(0) 2008年04月
  • 137) 閉塞性肥大型心筋症に対し経皮的中隔心筋焼灼術を施行した一例(第104回日本循環器学会近畿地方会)
    角野 元彦, 羽野 嘉文, 北川 直孝, 松本 祐一, 八尾 武憲, 山根 哲信, 城 日加里, 山本 孝, 高島 弘行, 藤井 応理, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 72(0) 2008年04月
  • 150) PKP2遺伝子変異が同定された不整脈源性右室心筋症(ARVC)の1剖検例(第104回日本循環器学会近畿地方会)
    松本 祐一, 長岡 伊織, 伊藤 誠, 堀江 稔, 西尾 由貴子, 杉原 洋行, 川嶋 剛史
    Circulation journal : official journal of the Japanese Circulation Society 72(0) 2008年04月
  • Noninvasive identification of myocardial sympathetic and metabolic abnormalities in a patient with "Takotsubo" cardiomyopathy
    Shinro Matsuo, Tetsuya Matsumoto, Ichiro Nakae, Daisuke Masuda, Masahiko Takada, Kiyoshi Murata, Minoru Horie
    International Medical Journal 12 143-144 2005年06月
  • 家庭用心電計による不整脈の検出 : 非伝送携帯型心電計による検討
    伊藤 誠, 稲垣 菊代, 芦原 貴司, 中澤 優子, 城 日加里, 伊藤 英樹, 八尾 武憲, 杉本 喜久, 坂口 知子, 岡 優子, 堀江 稔, 桝野 みどり, 金光 陽子, 楠本 和也, 山本 則仁
    心電図 = Electrocardiology 28 "S-1-21"-"S-1-22" 2008年03月
  • 心房細動と遺伝子異常 (特集 変革する心房細動診療とその実践up-to-date)
    牧山 武, 赤尾 昌治, 堀江 稔
    内科 101(3) 517-521 2008年03月
  • 心不全のバイオマーカー--心腎相関 (第1土曜特集 心血管マルチバイオマーカー・ストラテジー) -- (心血管マルチバイオマーカー・ストラテジー)
    蔦本 尚慶, 堀江 稔
    医学のあゆみ 224(5) 318-325 2008年02月
  • 第21回犬山不整脈カンファランスメインテーマ不整脈の成因と治療戦略テーマI「不整脈の新しい分子メカニズム」:心臓イオンチャネル遺伝子の転写制御機構~エピジェネティックスと機能分化~
    鷹野 誠, 倉富 忍, 堀江 稔, 斉藤 能彦, 桑原 宏一郎
    心電図 27(3) 15-28 2007年
  • Additional Gene Variants Reduce Effectiveness of Beta-Blockers in the LQT1 Form of Long QT Syndrome
    Atsushi Kobori, Nobuaki Sarai, Wataru Shimizu, Yoshihide Nakamura, Yosuke Murakami, Takeru Makiyama, Seiko Ohno, Kotoe Takenaka, Tomonori Ninomiya, Yuichiro Fujiwara, Satoshi Matsuoka, Makoto Takano, Akinori Noma, Toru Kita, Minoru Horie, Minoru Horie
    Journal of Cardiovascular Electrophysiology 15 190-199 2004年02月
    Introduction: Beta-blockers are widely used to prevent the lethal cardiac events associated with the long QT syndrome (LQTS), especially in KCNQ1-related LQTS (LQT1) patients. Some LQT1 patients, however, are refractory to this therapy. Methods and Results: Eighteen symptomatic LQTS patients (12 families) were genetically diagnosed as having heterozygous KCNQ1 variants and received beta-blocker therapy. Cardiac events recurred in 4 members (3 families) despite continued therapy during mean follow-up of 70 months. Three of these patients (2 families) had the same mutation [A341V (KCNQ1)]; and the other had R243H (KCNQ1). The latter patient took aprindine, which seemed to be responsible for the event. By functional assay using a heterologous mammalian expression system, we found that A341V (KCNQ1) is a loss-of-function type mutation (not dominant negative). Further genetic screening revealed that one A341V (KCNQ1) family cosegregated with S706C (KCNH2) and another with G144S (KCNJ2). Functional assay of the S706C (KCNH2) mutation was found to reduce the current density of expressed heterozygous KCNH2 channels with a positive shift (+8 mV) of the activation curve. Action potential simulation study was conducted based on the KYOTO model to estimate the influence of additional gene modifiers. In both models mimicking LQT1 plus 2 and LQT1 plus 7, the incidence of early afterdepolarization was increased compared with the LQT1 model under the setting of beta-adrenergic stimulation. Conclusion: Multiple mutations in different LQTS-related genes may modify clinical characteristics. Expanded gene survey may be required in LQT1 patients who are resistant to beta-blocker therapy.
  • 不整脈予防におけるARB, ACE阻害薬とアルドステロン拮抗薬 : アルドステロン拮抗薬と心室リモデリング
    蔦本 尚慶, 林 優, 田中 俊成, 西山 敬三, 山本 孝, 山路 正之, 藤井 応理, 伊藤 誠, 堀江 稔
    心電図 = Electrocardiology 28(1) 22-31 2008年01月
  • Bedside Teaching BNP測定における心不全患者の管理
    蔦本 尚慶, 堀江 稔
    呼吸と循環 52(2) 185-189 2004年02月
  • 採血でどこまでわかるか (心臓病のすべて) -- (心臓病を見つける)
    蔦本 尚慶, 堀江 稔
    からだの科学(257) 48-54 2008年
  • Thrombotic microangiopathy in an adult patient with clinically amyopathic dermatomyositis complicated with interstitial lung disease [2]
    Toshiro Sugimoto, Toshiro Sugimoto, T. Hajiro, T. Fujimoto, N. Kojyo, M. Horie, A. Kashiwagi
    Lupus 16 1004-1005 2007年12月
  • 心不全のバイオマーカー ー心腎相関
    医学のあゆみ 224(5) 318-325 2008年
  • 第38回河口湖心臓討論会 「分子生物学から見た循環器疾患」イオンチャネルと循環器疾患
    堀江 稔
    心臓 37(1) 83-92 2005年
    ヒト・ゲノム・プロジェクトに先行して,興奮性細胞膜に多く発現するイオン・チャネル分子のクローニングやその機能解析は,種々の遺伝子導入法とパッチ・クランプの進歩に伴い急速に行われていたが,1990年代に入って,遺伝的に重症不整脈を起こす一群の病気が,詳細な遺伝解析の結果,判明した.最初に報告されたのは,家族性QT延長症候群の患者においてであり,心臓の興奮とその伝導に重要な働きをする心筋ナトリウム・チャネル(SCN5A)と再分極を調節する遅延整流カリウム・チャネル遺伝子(KCNH2)の種々な変異であった.その後,ヒトにおいて重要な,もう一つの遅延整流カリウム・チャネルをコードするKCNQ1遺伝子にも,異常が発見され,以前から連鎖解析法で調べられLQT1と呼ばれていたグループの原因遺伝子であることが判明した. このような研究がきっかけとなって,心筋イオン・チャネル病の研究は,この10年近くの間に急速に進んだ.
  • 心房筋リモデリングを考慮したヒト心房細動in silicoモデルにおけるアミオダロンの急性効果と慢性効果
    PROGRESS IN MEDICINE 28(1) 562-567 2008年
  • Syndrome X
    Tetsuya Matsumoto, Minoru Horie, Kenichi Mitsunami
    Nippon rinsho. Japanese journal of clinical medicine Suppl 5 Pt 2 143-146 2007年09月
  • BNP検査の総説 : NT-proBNP検査時代を迎えて
    蔦本 尚慶, 堀江 稔
    臨床病理 = THE OFFICIAL JOURNAL OF JAPANESE SOCIETY OF LABORATORY MEDICINE 55 2007年10月
  • Atrial fibrillation up to date. 4) Are prevention and modification of atrial remodeling possible?
    Minoru Horie
    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 96 1909-1911 2007年09月
  • 107)右房内肉腫による上大静脈症候群に対しステント留置術を施行した一例(第103回日本循環器学会近畿地方会)
    藤井 応理, 河原 千穂, 高島 弘行, 松本 鉄也, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年10月
  • 74)新たなHERG遺伝子異常を認めた遺伝性QT延長症候群の一家系(第102回日本循環器学会九州地方会)
    安田 潮人, 加治 良一, 小田代 敬太, 中村 洋文, 辛島 詠士, 島津 秀樹, 深田 光敬, 中司 元, 丸山 徹, 宗内 淳, 堀江 稔, 辻 敬子
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年10月
  • 単一遺伝子病とゲノム(5)循環器疾患(2)不整脈
    堀江 稔
    ゲノム医学 7(3) 219-223 2007年10月
  • Romano-Ward syndrome
    Minoru Horie
    Nippon rinsho. Japanese journal of clinical medicine Suppl 4 230-233 2007年08月
  • Effect of angiotensin II receptor blockade on derived central arterial waveforms in hypertension
    Shinro Matsuo, Ichiro Nakae, Minoru Horie, Tetsuhiro Yamada, Yasuyuki Nakamura, Yasukazu Uchida, Yuichi Sato, Naoya Matsumoto
    Japanese Pharmacology and Therapeutics 35 801-807 2007年08月
    Objectives Arterial hypertension leads to vascular functional and structural adaptive processes which are related to angiotensin II. Analysis of the blood pressure (BP) waveform in the radial artery was introduced into clinical studies to characterize arterial properties by augmentation index (AI) or central blood pressure. The present study examined whether such properties were particularly responsive to angiotensin II receptor blocker therapy. Methods A total of 27 patients (63 ± 2.4 years) with essential hypertension [BP 152.8 ± 5.1/84.7 ± 4.0mmHg] were treated with olmesartan based on international guidelines. Radial artery pressure wave, including AI and BP2 (late systolic blood pressure), were determined by using an automatic cuff oscillometric device before and after therapy. Results Antihypertensive treatment with olmesartan [21.7 ± 1.7mg/day] significantly reduced brachial BP (152.8 ± 5.1 mmHg vs. 133.8 ± 3.3 mmHg, p = 0.0028) and BP2 (140.0 ± 5.1 mmHg vs. 120.3 ± 3.3 mmHg, p = 0.0006). AI decreased after 8 weeks of antihypertensive therapy (84.56 ± 2.58% vs. 76.85 ± 2.74%, p = 0.046). Plasma level of high sensitive C reactive protein was significantly decreased (0.462 ± 0.061 mg/dL vs. 0.202 ± 0.027 mg/dL, p = 0.003). Conclusions Olmesartan treatment reduces the AI as well as blood pressure in hypertensive patients.
  • Disorders of cardiac repolarization long QT and short QT syndromes
    Minoru Horie, Minoru Horie, Hideki Itoh
    Circulation Journal 71 2007年07月
    The long and short QT syndromes are heterogeneous diseases characterized by abnormal ventricular repolarization and episodes of syncope and/or life-threatening cardiac arrhythmias. Several disease-causing genes have been identified, including those encoding cardiac ion channel-composing proteins. The clinical determination of genotype offers a striking benefit: diagnosis, prediction of clinical phenotype, risk stratification, clinical and genetic counseling, and introduction of therapy. Genetic testing is of special importance for the genotyped patient's family members to prevent unexpected cardiac death. By means of recently advanced methodology in molecular genetics and electrophysiology it is expected that novel genes responsible for these disease entities will be identified.
  • 心房細動 up to date : 4)心房リモデリングの予防と改善は可能か
    堀江 稔
    日本内科学会雑誌 96(9) 1909-1911 2007年09月
  • Protective mechanism of adenosine to the rat arterial endothelial dysfunction induced by hydrogen peroxide
    Jun Lu, Shu Ming Zhu, Wei Jin Zang, Wei Jin Zang, Xiao Li Xu, Hong Li Luo, Xiao Jiang Yu, Sheng Peng Wang, Shan Shan Kong, Jie Wu, Jie Wu, Minoru Horie, Lei Sun
    Biological and Pharmaceutical Bulletin 30 1206-1211 2007年07月
    This study was designed to examine the in vitro effects of adenosine (Ado) on hydrogen peroxide-induced endothelial dysfunction in rats. Endothelial dysfunction was induced by exposing isolated rat mesenteric arteries to hydrogen peroxide (0.5 mM) for 12 h using an organ culture system. The protective effects of adenosine were tested by exposing isolated mesenteric arteries to adenosine (3 × 10 -7 mol/l, 10 -6 mol/l, 3 × 10 -6 mol/l) + hydrogen peroxide (0.5 mM) for 12 h. This exposure to hydrogen peroxide induced a significant concentration-dependent inhibition of endothelium-dependent relaxation (EDR). Coculture of segments of mesenteric artery with adenosine (3 × 10 -7 , 10 -6 , and 3 × 10 -6 mol/l) attenuated the hydrogen peroxide-induced impairment of vasorelaxation. This impairment was accompanied by a reduction in nitrite/nitrate, nitric oxide (NO) synthase (NOS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and an increasing in malondislehyde (MDA) and lactate dehydrogenase (LDH) activities in the aorta. These results indicate that adenosine can be used to attenuate hydrogen peroxide-induced endothelial dysfunction, an effect that may be related to antioxidation, thus enhancing NO production by preventing the decrease in NOS. © 2007 Pharmaceutical Society of Japan.
  • 30-P3-1 調剤併設型ドラッグストアにおける携帯型心電計を用いた不整脈治療の病診連携への参加(地域連携・薬薬連携・その他,社会の期待に応える医療薬学を)
    奥村 朋子, 榊原 幹夫, 小栗 正寛, 島田 繁, 岡田 啓, 沢村 昭人, 荒井 恵二, 堀江 稔, 伊藤 誠, 芦原 貴司, 稲垣 菊代
    日本医療薬学会年会講演要旨集 17 2007年09月
  • QT延長症候群(先天性,後天性) (不整脈検査) -- (不整脈と疾病)
    坂口 知子, 堀江 稔
    臨床検査 51(7) 764-768 2007年07月
  • 1)ステントを留置せずに治療し得た抗リン脂質抗体症候群の若年発症急性心筋梗塞の一例(第102回日本循環器学会近畿地方会)
    松本 祐一, 楢谷 康弘, 吉野 知秀, 羽野 嘉文, 高山 智行, 環 愼二, 岡林 旅人, 川嶋 剛史, 山本 孝, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年04月
  • 48)心房細動に対する拡大肺静脈隔離術後における携帯型心電計の有用性(第102回日本循環器学会近畿地方会)
    芦原 貴司, 中澤 優子, 八尾 武憲, 城 日加里, 伊藤 英樹, 八木 崇文, 杉本 喜久, 伊藤 誠, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年04月
  • 49)不整脈源性右室心筋症に対してICD植え込み術を施行した一例(第102回日本循環器学会近畿地方会)
    四方田 真紀子, 松尾 信郎, 芦原 貴司, 八尾 武憲, 杉本 喜久, 松本 鉄也, 伊藤 誠, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年04月
  • 52)前心室間静脈からのペーシング波形がVTと一致したが,大動脈弁左冠尖からの高周波通電により根治したsustained VTの一例(第102回日本循環器学会近畿地方会)
    國友 健生, 伊藤 英樹, 伊藤 誠, 八尾 武憲, 中澤 優子, 芦原 貴司, 城 日加里, 堀江 稔, 杉本 喜久
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年04月
  • 59)心筋リアノジン受容体(hRYR2)の遺伝子変異を有したカテコラミン誘発性多形性心室頻拍(CPVT)の2症例(第102回日本循環器学会近畿地方会)
    道智 賢市, 松本 祐一, 長岡 伊織, 八尾 武憲, 坂口 知子, 中澤 優子, 岡 優子, 伊藤 英樹, 芦原 貴司, 伊藤 誠, 堀江 稔, 住友 直方, 鷹津 良樹
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年04月
  • 117)糖尿病患者における冠動脈病変と冠動脈石灰化スコアの関連性の検討(第102回日本循環器学会近畿地方会)
    大村 寧, 近藤 基之, 本田 亘, 卯木 智, 西尾 善彦, 前川 聡, 柏木 厚典, 高島 弘行, 堀江 稔, 門脇 崇, 上島 弘嗣, 鈴木 英司, 吉村 達
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年04月
  • The role of impaired sympathetic nerve function in enhancing coronary vasoconstriction in patients with hypertrophic cardiomyopathy
    Shinro Matsuo, Tetsuya Matsumoto, Ichiro Nakae, Minoru Horie
    Experimental and Clinical Cardiology 12 37-41 2007年04月
    Coronary vasospasm and diminished coronary blood flow reserve have often been reported in patients with hypertrophic cardiomyopathy (HCM). However, the mechanism of coronary spasm in HCM is unknown. Thus, coronary endothelial function and sympathetic nerve function in 11 patients with HCM and 11 control patients matched for age and sex were examined. The diameter of the left anterior descending coronary artery was assessed by quantitative coronary angiography, and the change in coronary blood flow was estimated using an intracoronary Doppler flow wire. To assess myocardial sympathetic nerve function, metaiodobenzylguanidine images - 15 min and 180 min after the injection of 1231-metaiodoben-zylguanidine at a dosage of 111 MBq - were obtained, and the heart to mediastinum (H/M) count ratio and the washout rate MR) were calculated. The H/M ratio was significantly lower in patients with HCM (2.1±0.3) than in control patients (2.6±0.4) (P < 0.01). In addition, the WR was higher in patients with HCM (35±6%) than in control patients (28±3%) (P < 0.01). The HCM subjects with coronary spasm had lower H/M ratios and higher WRs than HCM subjects without coronary spasm (P < 0.05, respectively). In conclusion, impaired sympathetic nerve function may be associated with coronary vasospasm and diminished coronary blood flow reserve in HCM. © 2007 Pulsus Group Inc. All rights reserved.
  • 118)早朝高血圧とメタボリックシンドローム(第102回日本循環器学会近畿地方会)
    環 愼二, 吉野 知秀, 松本 祐一, 高山 智行, 樽谷 康弘, 岡林 旅人, 川嶋 剛史, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年04月
  • Churg-Strauss syndrome presenting with massive pericardial effusion
    Shinro Matsuo, Yuichi Sato, Tetsuya Matsumoto, Nobu Naiki, Minoru Horie
    Heart and Vessels 22 128-130 2007年03月
    We describe a case of Churg-Strauss syndrome (CSS) presenting with a massive pericardial effusion without overt myocardial dysfunction. A 60-year-old man was referred to our hospital because of exertional dyspnea and fever. Initial chest multidetector-row computed tomography showed a massive pericardial effusion. The presence of eosinophilia, infiltrates of both lungs, pathological evidence of necrotizing vasculitis associated with eosinophilic infiltration, and history of asthma fulfilled the criteria of CSS. Massive pericardial effusion can be the first manifestation of cardiac involvement in CSS. © Springer-Verlag Tokyo 2007.
  • 126)急性心筋梗塞後チクロピジンにて血栓性血小板減少性紫斑病をきたした1例(第102回日本循環器学会近畿地方会)
    河原 千穂, 谷口 晋, 高島 弘行, 山本 孝, 松本 鉄也, 堀江 稔, 浜本 徹, 辻田 靖之, 江口 豊
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年04月
  • Relationship between metabolic syndrome and Trp64Arg polymorphism of the β3-adrenergic receptor gene in a general sample: The Shigaraki study
    Shinji Tamaki, Yasuyuki Nakamura, Yasuharu Tabara, Tomonori Okamura, Yoshikuni Kita, Takashi Kadowaki, Yasuyuki Tsujita, Minoru Horie, Tetsuro Miki, Hirotsugu Ueshima
    Hypertension Research 29 891-896 2006年11月
    It has been reported that the β3-adrenergic receptor gene (ADRB3) is associated with abnormal metabolic risk factors. Therefore, we examined whether the Trp64Arg polymorphism of ADRB3 affects the occurrence of metabolic syndrome (MS). The participants were 2,395 subjects who underwent a medical examination in Shigaraki in Shiga, Japan. Among them, 1,416 subjects who gave informed consent for genetic analysis and were not receiving treatment for hypertension, diabetes, or hyperlipidemia were enrolled in this study. MS was diagnosed in 86 (16.0%) of 537 men, and 8 (0.9%) of 879 women. Ther e was no significant relationship between ADRB3 polymorphism and the frequency of MS. Multiple logistic regression analysis including smoking, sex, and age as confounding factors showed no interaction between MS and ADRB3 polymorphism (odds ratio: 0.94; 95% confidence interval: 0.59-1.49; p=0.78). Subjects were also analyzed according to differences in the number of abnormal metabolic risk factors. However, there was no significant relationship between ADRB3 polymorphism and the number of such factors. In conclusion, in a general sample, the frequency of MS as 16.0% in men, and 0.9% in women. There was no relationship between ADRB3 polymorphism and MS.
  • 132)妊娠12週で急性大動脈解離を発症したMarfan症候群の一例(第102回日本循環器学会近畿地方会)
    寺村 真範, 高橋 聡文, 藤井 応理, 松本 鉄也, 堀江 稔, 四方 寛子, 野田 洋一, 辻田 靖之, 浜本 徹, 江口 豊
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年04月
  • Response to letter regarding article, "angiotensin II potentiates the slow component of delayed rectifier K+ current via the AT1 receptor in guinea pig atrial myocytes" [2]
    Dimitar P. Zankov, Mariko Omatsu-Kanbe, Futoshi Toyoda, Wei Guang Ding, Hiroshi Matsuura, Takahiro Isono, Minoru Horie
    Circulation 114 2006年10月
  • 161)急性心不全をきっかけに判明した右冠動脈肺動脈起始症の一例(第102回日本循環器学会近畿地方会)
    羽野 嘉文, 岡林 旅人, 吉野 知秀, 松本 祐一, 高山 智行, 樽谷 康弘, 環 信二, 川嶋 剛史, 山本 孝, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年04月
  • Primary malignant lymphoma of the right atrium resulting in superior vena caval syndrome in an HIV-positive patient: depiction at multislice computed tomography and magnetic resonance imaging
    Shinro Matsuo, Yuichi Sato, Akashi Miyamoto, Ichiro Nakae, Michio Saeki, Keiko Hodohara, Minoru Horie
    Cardiovascular Revascularization Medicine 7 255-257 2006年10月
    An HIV-positive 32-year-old male presenting with superior vena cava syndrome underwent multislice computed tomography (MSCT) and magnetic resonance imaging (MRI), which showed a large tumor in the right atrium, which extended to the superior vena cava. Pathologic examination revealed that the mass was consistent with B cell-type malignant lymphoma. The tumor size markedly decreased after the initiation of chemotherapy and patient recovery has been uneventful for 1 year. © 2006 Elsevier Inc. All rights reserved.
  • Novel mutation of plakophilin-2 associated with arrhythmogenic right ventricular cardiomyopathy
    Iori Nagaoka, Keiji Matsui, Takeshi Ueyama, Masashi Kanemoto, Jie Wu, Akihiko Shimizu, Masunori Matsuzaki, Minoru Horie, Minoru Horie
    Circulation Journal 70 933-935 2006年07月
    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease characterized by dilatation and akinesis of the right ventricle, and causes life-threatening ventricular arrhythmia. Mutations of plakophilin-2 (PKP2) have recently been identified as one causative abnormality in ARVC. A case of ARVC with a mutation of PKP2 is reported here. Direct sequencing of the patient's DNA revealed an insertion mutation in exon 8 of PKP2 (1728_1729insGATG). The mutation caused the frameshift and the premature termination of translation (R577DfsX5). This is the first case report of PKP2 mutation found in Japanese ARVC patients.
  • alpha-Adducin gene
    Shinji Tamaki, Yasuyuki Nakamura, Minoru Horie, Masahiko Kinoshita, Naoharu Iwai
    Nippon rinsho. Japanese journal of clinical medicine. 64 Suppl 5 348-352 2006年07月
  • Tumor necrosis factor-α inhibits the cardiac delayed rectifier K current via the asphingomyelin pathway
    Katsuharu Hatada, Takashi Washizuka, Minoru Horie, Hiroshi Watanabe, Fumio Yamashita, Masaomi Chinushi, Yoshifusa Aizawa
    Biochemical and Biophysical Research Communications 344 189-193 2006年05月
    Tumor necrosis factor-α (TNF-α) affects contractility and ionic currents in the heart. However, the electrophysiological effects, especially on delayed rectifier K currents (IK), have not yet been fully elucidated. We examined the effects of TNF-α on IK. Using a voltage-clamp method, IK was measured in guinea pig ventricular myocytes in the basal state and after pharmacological intervention. To specify the site of the action of TNF-α, the myocytes were incubated with pertussis toxin or N-oleoylethanolamine, a ceramidase inhibitor, and IK was measured. TNF-α suppressed IK when it was enhanced by isoproterenol, histamine or forskolin but not in the basal state or when IK was augmented by an internal application of cyclic AMP. Both pre-incubation with pertussis toxin and N-oleoylethanolamine abolished the inhibitory action of TNF-α on isoproterenol-augmented IK. TNF-α inhibits IK, mainly IKs, when it is augmented by PKA as a result of the generation of sphingosine. © 2006 Elsevier Inc. All rights reserved.
  • Scintigraphic evaluation of cardiac metabolism and sympathetic nerve function in alcoholic cardiomyopathy
    Shinro Matsuo, Ichiro Nakae, Daisuke Masuda, Tetsuya Matsumoto, Minoru Horie
    Internal Medicine 45 465-467 2006年05月
    A 70-year-old man with alcoholic cardiomyopathy underwent 99m technetium-sestamibi (MIBI), iodine-123-labeled metaiodobenzylguanidine (MIBG) scintigraphy and Iodine-123-labeled beta-methyl-iodophenyl pentadecanoic acid (BMIPP) scintigraphy. 99m Technetium-MIBI identified myocardial damage in the inferior wall of left ventricle. 123 I BMIPP showed low uptake in the inferior wall of the myocardium, concordant to perfusion. 123 I BMIPP and 123 I MIBG showed reduced uptake in the inferior segment of the myocardium, indicating impairment of fatty acid metabolism and sympathetic abnormalities. Damaged myocardium was demonstrated in alcoholic cardiomyopathy. Beta blocker (carvedilol) and angiotensin-receptor blocker (valsartan) were started at low doses, then increased gradually, leading to the improvement of cardiac performance. Cardiac sympathetic nerve function, impaired due to alcoholic cardiomyopathy, was improved with beta-blocker therapy. Cardiac scintigraphy may be useful to assess the extent of myocardial improvement and the response to therapy. © 2006 The Japanese Society of Internal Medicine.
  • The Jervell and Lange-Nielsen syndrome: Natural history, molecular basis, and clinical outcome
    Peter J. Schwartz, Peter J. Schwartz, Peter J. Schwartz, Carla Spazzolini, Lia Crotti, Lia Crotti, Jørn Bathen, Jan P. Amlie, Katherine Timothy, Maria Shkolnikova, Charles I. Berul, Charles I. Berul, Maria Bitner-Glindzicz, Lauri Toivonen, Minoru Horie, Eric Schulze-Bahr, Eric Schulze-Bahr, Isabelle Denjoy, Isabelle Denjoy, Isabelle Denjoy
    Circulation 113 783-790 2006年02月
    Background - Data on the Jervell and Lange-Nielsen syndrome (J-LN), the long-QT syndrome (LQTS) variant associated with deafness and caused by homozygous or compound heterozygous mutations on the KCNQ1 or on the KCNE1 genes encoding the I Ks current, are still based largely on case reports. Methods and Results - We analyzed data from 186 J-LN patients obtained from the literature (31%) and from individual physicians (69%). Most patients (86%) had cardiac events, and 50% were already symptoma tic by age 3. Their QTc was markedly prolonged (557±65 ms). Most of the arrhythmic events (95%) were triggered by emotions or exercise. Females are at lower risk for cardiac arrest and sudden death (CA/SD) (hazard ratio, 0.54; 95% CI, 0.34 to 0.88; P=0.01). A QTc > 550 ms and history of syncope during the first year of life are independent predictors of subsequent CA/SD. Most mutations (90.5%) are on the KCNQ1 gene; mutations on the KCNE1 gene are associated with a more benign course. β-Blockers have only partial efficacy; 51% of the patients had events despite therapy and 27% had CA/SD. Conclusions - J-LN syndrome is a most severe variant of LQTS, with a very early onset and major QTc prolongation, and in which β-blockers have limited efficacy. Subgroups at relatively lower risk for CA/SD are identifiable and include females, patients with a QTc ≤550 ms, those without events in the first year of life, and those with mutations on KCNE1. Early therapy with implanted cardioverter/defibrillators must be considered. © 2006 American Heart Association, Inc.
  • Recent topics on diagnosis and therapy for arrhythmia
    Minoru Horie
    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 95 520-523 2006年01月
  • Arrhythmia and the pathogenetic gene
    Hideki Ito, Minoru Horie
    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 95 203-208 2006年01月
  • Inhibition of aldosterone and endothelin-1 by carperitide was attenuated with more than 1 week of infusion in patients with congestive heart failure
    Chitose Ishikawa, Takayoshi Tsutamoto, Atsuyuki Wada, Masanori Fujii, Keijin Ohno, Hiroshi Sakai, Takashi Yamamoto, Minoru Horie
    Journal of Cardiovascular Pharmacology 46 513-518 2005年10月
    Short-term infusion of carperitide (atrial natriuretic peptide) has beneficial effects on neurohumoral factors; however, it remains unclear whether the effects are sustained for long-term infusion. To evaluate the effects of long-term infusion of carperitide on neurohumoral factors in patients with chronic congestive heart failure (CHF), we measured neurohumoral factors before and 1 hour after stopping carperitide infusion in 42 CHF patients. Carperitide infusion was continued for more than 2 days until there was symptomatic improvement of CHF. Patients were divided into 2 groups by the median value of infusion duration: group 1 (less than 7 days, n = 21) and group 2 (more than 7 days, n = 21). In group 1, aldosterone (ALD) and endothelin-1 (ET-1) were significantly increased after stopping carperitide. In contrast, ALD and ET-1 did not change after stopping carperitide in group 2. The molar ratio of cyclic guanosine monophosphate/atrial natriuretic peptide before stopping carperitide was significantly lower in group 2 than in group 1. Suppression of ALD and ET-1 was maintained for 7 days of carperitide infusion, but the beneficial effect on neurohumoral factors was attenuated after more than 7 days, probably through down-regulation of biologic receptors coupled with guanylate cyclase in CHF patients. Copyright © 2005 by Lippincott Williams & Wilkins.
  • Left ventricular systolic/diastolic function evaluated by quantitative ECG-gated SPECT: Comparison with echocardiography and plasma BNP analysis
    Ichiro Nakae, Ichiro Nakae, Shinro Matsuo, Terue Koh, Kenichi Mitsunami, Minoru Horie
    Annals of Nuclear Medicine 19 447-454 2005年09月
    Objective: The aim of this study was to evaluate the left ventricular (LV) functional parameters calculated using quantitative electrocardiography (ECG)-gated myocardial perfusion single photon emission computed tomography (QGS). In addition to LV systolic parameters, diastolic parameters were compared with those by ultrasound echocardiography (UCG) and also with plasma B-type natriuretic peptide (BNP) concentrations. Methods: We examined 46 patients with various forms of heart disease. By the QGS data with 16 framing data acquisition using technetium (Tc)-99m methoxyisobutylisonitrile (MIBI) perfusion, we calculated the following parameters: LV end-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), peak filling rate (PFR), filling rate during the first third of the filling time (1/3FR) and first third filling fraction (1/3FF). By UCG, we measured mitral early to atrial (E/A) wave velocity ratio and pulmonary venous inflow systolic/diastolic (S/D) ratio as diastolic functional parameters. Plasma BNP concentrations were also measured. Results: There was a significant correlation between LVEDV, ESV and EF measured by QGS and UCG (EDV, r = 0.71, p < 0.001; ESV, r = 0.82, p < 0.001 ; EF, r = 0.75, p < 0.001). The PFR, 1/3FR and 1/3FF obtained by QGS correlated positively with E/A ratio (PFR, r = 0.54, p < 0.001; 1/3FR, r = 0.61, p < 0.001; 1/3FF, r = 0.42, p < 0.01) and negatively with S/D ratio (PFR, r = -0.40, p < 0.01; 1/3FR, r = -0.38, p < 0.05; 1/3FF, r = -0.39, p < 0.01) obtained by UCG. Plasma BNP concentrations in EF < 50% patients were greater than those in EF ≥ 50% patients (335.2 ± 60.2 vs. 101.2 ± 41.3 pg/ml, p < 0.01, both n = 17). Plasma BNP levels were also compared between higher and lower 1/3FF patients matched for LVEF. Plasma BNP concentrations in 1/3FF < 35% patients were significantly greater than those in 1/3FF > 35% patients (312.9 ± 62.5 vs. 120.5 ± 32.8 pg/ml, p < 0.05, both n = 14). Conclusions: The degree of LV systolic and diastolic dysfunctions evaluated by QGS correlated with that by UCG or BNP. The QGS functional parameters offer useful information regarding cardiac failure.
  • Clinical significance of plasma BNP measurement in patients with pychiatric disease
    Ichiro Nakae, Shinro Matsuo, Terue Koh, Kenichi Mitsunami, Minoru Horie
    International Medical Journal 12 181-184 2005年09月
    Objective: Plasma BNP concentration is a useful marker of cardiac dysfunction which reflects the disease severity. It has been reported that antipsychotic agent may cause fatal cardiac complications along with QT prolongation on electrocardiogram. To investgate potentially progressive cardiac complications by antipsychotic agents, we examined plasma BNP concentrations in schizophrenic patients. Design: A clinical study. Methods: Plasma BNP concentrations in 60 inpatients with schizophrenia were examined. All patients were treated with antipsychotic agents for more than 1 year. The patients with cardiac disease, hypertension, renal dysfunction or diabetes mellitus were excluded. Results: Plasma BNP concentrations were significantly higher in schizophrenic patients than in age-matched normal controls (25.0 ± 56.8 vs 13.1 ± 11.2 pg/ml, p < 0.05). In 5 patients who exhibited higher plasma BNP concentrations, echocardiography failed to detect the abnormality of left ventricular dimension or systolic function. However, plasma BNP concentration correlated positively with the QT interval corrected for heart rate (QTc), suggesting cardiac alteration by antipsychotic agents. Conclusions: Our study suggests that cardiac complications may be potentially advanced in patients treated with antipsychotic agents. The measurement of plasma BNP may be useful for detecting cardiac complications in the early stage. © 2005 Japan International Cultural Exchange Foundation.
  • Combined analysis of polymorphisms in angiotensinogen and adducin genes and their effects on hypertension in a Japanese sample: The Shigaraki study
    Shinji Tamaki, Yasuyuki Nakamura, Yasuharu Tabara, Tomonori Okamura, Yoshikuni Kita, Takashi Kodawaki, Yasuyuki Tsujita, Minoru Horie, Tetsuro Miki, Hirotsugu Ueshima
    Hypertension Research 28 645-650 2005年08月
    We examined the interactions between lifestyle and polymorphisms of salt-sensitive genes and their effects on hypertension in a general Japanese sample (The Shigaraki Study). The study group consisted of 2,902 subjects who underwent a medical examination in 1999 in Shigaraki, a suburban area in Shiga. Among 1,647 subjects not receiving antihypertensive medication, in a combined analysis of angiotensinogen (AGT) and adducin (ADD1) polymorphisms, double homozygosity of 235Trp or 460Trp was not found to be associated with hypertension. A multiple logistic regression analysis showed that age (odds ratio [OR]: 1.07, 95% confidence interval [95% CI] : 1.06-1.08), body mass index (BMI) (OR: 1.18, 95% CI: 1.13-1.23), alcohol consumption (OR: 1.39, 95% CI: 1.16-1.66), family history of hypertension (OR: 1.57, 95% CI: 1.18-2.07), and combined AGT M235T Thr/Thr and ADD1 Trp/Trp polymorphisms (OR: 1.37, 95% CI: 1.03-1.82) were associated with hypertension. However, there was no interaction between eating salty food and combined AGT and ADD1 polymorphisms. Furthermore, eating salty food was not associated with hypertension in a multivariate analysis. Therefore, a combination of the AGT and ADD1 polymorphisms appears to be associated with hypertension. However, a sim ple questionnaire regarding salt intake was not sufficient to confirm the relationship between salt intake and hypertension and/or salt-sensitive genes.
  • フォーラム 遺伝性不整脈疾患--その診断と治療
    堀江 稔
    セフィーロ(3) 75-78 2006年
  • Effect of statin therapy on arterial stiffness in patients with hyperlipidemia: Shiga pravastatin atherosclerosis study (SHIPAS) group
    Shinro Matsuo, Yasuyuki Nakamura, Tetsuhiro Yamada, Yasukazu Uchida, Ichiro Nakae, Minoru Horie
    Journal of Applied Research 5 397-401 2005年07月
    A man is as old as his arteries and the vascular remodeling is a common problem in the elderly. Aortic pulse wave velocity (PWV) provides noninvasive measurement of the mechanical properties of arteries. Objective: We measured the effects of HMA-CoA inhibitor (pravastatin) on arterial stiffness, ankle brachial index, PWV, and blood pressure (BP) in patients with hyperlipidemia. Design and Methods: The present study involved 15 patients (mean age 65 ± 2.7 years) with hyperlipidemia who were not on any medication. Aortic pulse wave velocity was evaluated at baseline and following 3 months of drug intake (pravastatin 10 mg/day). Twenty healthy volunteers constituted a control group. Results: Following 6 months of conventional treatments of hyperlipidemia, brachial systolic BP and diastolic BP did not change significantly with pravastatin from baseline (Not significant; NS). The PWV decreased significantly after treatment with pravastatin (1912 ± 90.3 vs 1755 ± 96.9 cm/sec, P < 0.001). There was no significant difference in control subjects (1677 ± 71.5 vs 1796 ± 56 cm/sec. NS). The decrease in PWV with pravastatin was independent of blood pressure (P < 0.05). Conclusions: The study shows that HMA-CoA inhibitor might improve arterial wall stiffness in patients with hyperlipidemia.
  • Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: Characteristic T-U-wave patterns predict the KCNJ2 genotype
    Li Zhang, Li Zhang, D. Woodrow Benson, Martin Tristani-Firouzi, Louis J. Ptacek, Rabi Tawil, Peter J. Schwartz, Alfred L. George, Minoru Horie, Gregor Andelfinger, Gregory L. Snow, Ying Hui Fu, Michael J. Ackerman, G. Michael Vincent, G. Michael Vincent, G. Michael Vincent
    Circulation 111 2720-2726 2005年05月
    Background - The ECG features of Andersen-Tawil syndrome (ATS) patients with KCNJ2 mutations (ATS1) have not been systematically assessed. This study aimed to define ECG features of KCNJ2 mutation carriers, to determine whether characteristic T-U-wave patterns exist, and to establish whether T-U patterns predict the ATS1 genotype. Methods and Results - In phase I, evaluation of T-U morphology in ECGs of 39 KCNJ2 mutation carriers identified characteristic T-U patterns: prolonged terminal T downslope, wide T-U junction, and biphasic and enlarged U waves. In phase II, ATS1 genotype prediction by T-U pattern was evaluated in the next 147 ECGs (57 other KCNJ2 mutation carriers, 61 unaffected family members, and 29 ATS patients without KCNJ2 mutations), with a sensitivity of 84% and specificity of 97%. Characteristic T-U patterns were present in 91% (87/96), in whom an enlarged U wave was predominant (73%). In phase III, QTc, QUc, and T- and U-wave duration/amplitude were compared in the 96 ATS1, 29 non-KCNJ2 ATS, and 75 normal subjects. In ATS1 patients, QUc, U-wave duration and amplitude, and QTc were all increased (P < 0.001), but median QTc and interquartile range (IQR) were just 440 ms (IQR, 28 ms) compared with 420 ms (IQR, 20 ms) in normal subjects and 425 ms (IQR, 48 ms) in ATS non-KCNJ2 patients. Conclusions - In ATS1 patients, gene-specific T-U-wave patterns resulting from decreased I K1 owing to KCNJ2 mutations can aid diagnosis and direct genotyping. The normal QTc, distinct ECG, and other clinical features distinguish ATS1 from long-QT syndrome, and it is best designated as ATS1 rather than LQT7. © 2005 American Heart Association, Inc.
  • Detection of calf muscle alterations in patients with chronic heart failure by 31P magnetic resonance spectroscopy: Impaired adaptation to continuous exercise
    Ichiro Nakae, Kenichi Mitsunami, Shinro Matsuo, Toshiro Inubushi, Shigehiro Morikawa, Terue Koh, Minoru Horie
    Experimental and Clinical Cardiology 10 4-8 2005年05月
    Previous studies suggested that alteration of systemic skeletal muscle metabolism is a major determinant of exercise tolerance in patients with chronic heart failure (CHF). The authors examined calf muscle metabolism during continuous exercise of the foot in patients with CHF compared with normal subjects using 31 p magnetic resonance spectroscopy. The subjects were patients with New York Heart Association class II CHF who had previously suffered New York Heart Association class IV heart failure. Plantarflexion of the foot was repeated for 8 min 40 s at a rate of one contraction per second against a 2 kg load inside the magnet. At rest, during exercise (divided into the first one-half [EX1] and the latter one-half [EX2] ) and at recovery, 31 p magnetic resonance spectroscopy data sets were acquired every 4 min 20 s. At rest, the phosphocreatine to hexamethylphosphoric triamide (PCr:HMPT) and the inorganic phosphate (Pi) to PCr ratios in the CHF group were not different from those in the normal group. During EX1 in the normal group, PCr levels decreased and Pi levels increased. Although exercise continued, these changes improved during EX2, suggesting there was an adaptation to exercise. The degree of change in the PCr:HMPT ratio during EX1 in the CHF group was not significantly different from that during EX1 in the normal group; however, the improvement during EX2 in the CHF group was impaired. The Pi:PCr ratio of EX1 to EX2 in the CHF group was significantly greater than that in the normal group (0.74±0.22 versus 0.19±0.05, respectively, P < 0.005). Thus, in CHF, adaptation to continuous exercise may be impaired by alteration of skeletal muscle metabolism and this alteration may worsen exercise capacity. © 2005 Pulsus Group Inc. All rights reserved.
  • Dilated cardiomyopathy relieved as a result of β-blocker therapy: A case report - Key points in assessment of prognosis based on MIBG myocardial scintigraphy and BNP levels
    Shinro Matsuo, Shinro Matsuo, Ichiro Nakae, Daisuke Masuda, Tetsuya Matsumoto, Minoru Horie
    Annals of Nuclear Medicine 19 243-246 2005年05月
    A 48-year-old male patient was admitted to our hospital with dyspnea accompanied by orthopnea. Chest x-rays showed a cardiothoracic ratio of 68% and pulmonary congestion. He was diagnosed with dilated cardiomyopathy. β-Blocker (carvedilol) therapy was initiated on Day 22 of the disease using a small initial dose. He was followed up based on BNP levels and MIBG scintigraphy. The H/M ratio and MIBG washout rate were 1.98 and 33.4%, respectively, on Day 20 and 2.15 and 28.1%, respectively, on Day 72. The patient was discharged on Day 72 when congestive heart failure improved. Relatively high BNP levels were observed for 1 month after starting treatment with a β-blocker. Plasma BNP levels were still as high when his heart failure was improved. BNP is useful as a convenient indicator for the severity of cardiac diseases. MIBG scintigraphy may be used thereafter to evaluate the severity in greater detail and more precisely determine the prognosis.
  • Regulation of the muscarinic K + channel by extracellular ATP through membrane phosphatidylinositol 4,5-bisphosphate in guinea-pig atrial myocytes
    Yoh Yasuda, Yoh Yasuda, Hiroshi Matsuura, Makoto Ito, Tetsuya Matsumoto, Wei Guang Ding, Minoru Horie
    British Journal of Pharmacology 145 156-165 2005年05月
    The present study was designed to examine the functional role of membrane phosphatidylinositol 4,5-bisphosphate (PtdIns(4,S)P 2 ) in the regulation of the muscarinic K + channel (I K.ACh ) by extracellular ATP and adenosine in guinea-pig atrial myocytes, using the whole-cell patch-clamp method. Bath application of ATP in micromolar concentrations typically evoked a transient activation of I K.ACh ; a rapid activation phase was consistently followed by a progressive decline even to the baseline level despite the continued presence of ATP. This progressive decline of I K.ACh was significantly attenuated either by blockade of phospholipase C (PLC) with compound 48/80 (100 μM) or by addition of PtdIns(4,5)P 2 (50 μM) to the cell inside, suggesting that depletion of membrane PtdIns(4,5)P 2 via PLC activation is mainly, if not totally, responsible for the progressive decline of I K.ACh during the presence of ATP. When atrial myocytes were exposed to wortmannin (50 μM) following ATP (50 μM) application to impair the resynthesis of PtdIns(4,5)P 2 , the activation of I K.ACh evoked by subsequently applied ATP (50 μM) was greatly reduced. Activation of I K.ACh by adenosine (100 μM) was partially reduced by pretreatment of atrial myocytes with ATP (100 μM) and was largely abolished by a further addition of wortmannin (50 μM) in the presence of ATP (100 μM). These results support the view that the activation of I K.ACh by ATP and adenosine depends on membrane PtdIns(4,5)P 2 that is subject to reduction by extracellular ATP. The present study thus provides functional evidence to suggest that extracellular ATP activates PLC and thereby depletes membrane PtdIns(4,5)P 2 that is critically involved in the activation process of I K.ACh by its agonists ATP and adenosine in guinea-pig atrial myocytes. © 2005 Nature Publishing Group. All rights reserved.
  • Double SCN5A mutation underlying asymptomatic Brugada syndrome
    Hisataka Yokoi, Naomasa Makita, Koji Sasaki, Yasuhiro Takagi, Yasuo Okumura, Tetsuo Nishino, Takeru Makiyama, Akira Kitabatake, Minoru Horie, Ichiro Watanabe, Hiroyuki Tsutsui
    Heart Rhythm 2 285-292 2005年03月
    Objectives: The purpose of this study was to identify risk markers in patients with Brugada syndrome. Background: Patients with Brugada syndrome who experience syncope or aborted sudden death are at high risk for recurrent lethal arrhythmias. The prognosis and therapeutic approaches in asymptomatic individuals with a Brugada-type ECG (asymptomatic Brugada syndrome) are controversial. Methods: We genetically screened 30 asymptomatic probands (29 men and 1 woman; mean age 47.1 years) exhibiting a spontaneous Brugada-type ECG. Family members of patients with Brugada syndrome were excluded from the study. Results: Twenty-nine of 30 patients (96.7%) remained symptom-free for at least 3 years. One patient (case 1) with a family history of sudden death died suddenly during sleep. Ventricular fibrillation was induced by programmed electrical stimulation in 14 of 18 subjects (78%), but none of these 18 subjects developed spontaneous ventricular arrhythmias. Genetic screening failed to identify SCN5A mutations in most cases but demonstrated a novel double missense mutation (K1527R and A1569P) located on the same allele in another asymptomatic subject (case 2). Heterologously expressed mutant Na channels exhibited a negative shift of steady-state inactivation (9.2 mV) and enhanced slow inactivation, suggesting this individual harbors a subclinical channel dysfunction compatible with symptomatic Brugada syndrome. Conclusions: Asymptomatic individuals with a Brugada-type ECG generally have a better prognosis than their symptomatic counterparts, but a subgroup of these individuals may have a poor prognosis. Severe Na channel dysfunction as a result of SCN5A mutations may not be sufficient to cause symptoms or arrhythmias in patients with Brugada syndrome, suggesting unknown factors or modifier genes influence arrhythmogenesis. © 2005 Heart Rhythm Society. All rights reserved.
  • Noninvasive evaluation of coronary artery plaque with electrocardiographically-gated multislice computed tomography
    Shinro Matsuo, Ichiro Nakae, Tetsuya Matsumoto, Minoru Horie
    CMIGExtra: Cases 29 13-18 2005年03月
    The study evaluated the feasibility of determining coronary lesion configuration, including coronary plaque, stenosis and calcification, by ECG-gated MSCT. The results were compared with the characteristics of intravascular ultrasound (IVUS). The overall sensitivity for diagnosing significant coronary stenosis was 80.2%, and the specificity was 95.6%. There were significant differences in plaque density among three groups (p < 0.01). MSCT was feasible for the detection of coronary artery stenosis. And plaque composition could be clearly differentiated and classified by MSCT, which is a promising method of non-invasive risk assessment in patients with known or suspected coronary artery disease. © 2005 Elsevier Ltd. All rights reserved.
  • Brachial artery flow-mediated vasodilation is correlated with coronary vasomotor and fibrinolytic responses induced by bradykinin
    Yasuhiro Tarutani, Tetsuya Matsumoto, Hiroyuki Takashima, Tetsunobu Yamane, Minoru Horie
    Hypertension Research 28 59-66 2005年01月
    Endothelium plays a key role in the regulation of not only vascular tone but also thrombosis and fibrinolysis. Brachial flow-mediated vasodilation (FMD) provides a noninvasive method of assessing coronary endothelial dysfunction. However, no data are available on the relationship between brachial FMD and coronary fibrinolytic activity. Thus, we examined the relationship between brachial FMD and coronary vasomotor and fibrinolytic function. Brachial FMD by reactive hyperemia was defined as a change in diameter relative to the baseline as measured using high-resolution ultrasound. Coronary blood flow (CBF) responses to bradykinin (BK) were analyzed using Doppler flow velocity measurement. Coronary release of tissue-type plasminogen activator (tPA) antigen was determined as the transcardiac tPA gradient × {CBF × (100 - hematocrity)/100}. In 77 patients with normal coronary arteries, BK caused dose-dependent increases in CBF, transcardiac tPA gradient, and coronary tPA release. Among them, brachial FMD, the BK-induced CBF increase, and the coronary tPA release induced by BK in 14 diabetic subjects were lower than those in 63 non-diabetic subjects (p < 0.05, respectively). Brachial FMD correlated with the CBF increase, transcardiac tPA gradient (0.2 μg/min: r=0.25; 0.6 μg/min: r=0.43; 2.0 μg/min: r=0.34; p < 0.05, respectively), and coronary tPA release (0.2 μg/min: r=0.24; 0.6 μg/min: r=0.44; 2.0 μg/min: r=0.32; p < 0.05, respectively) in response to BK. Brachial FMD correlated significantly with coronary endothelial function and fibrinolytic activity in response to BK. Type 2 diabetes impaired coronary and brachial endothelium-dependent vasodilation and coronary fibrinolytic activity.
  • Diagnosis of heart failure by measuring humoral factors
    Takayoshi Tsutamoto, Minoru Horie
    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 94 221-227 2005年01月
  • Cardiovascular imaging by means of multi-slice CT in cardiology.
    Shinro Matsuo, Minoru Horie
    Nippon Hoshasen Gijutsu Gakkai zasshi 61 1309-1317 2005年01月
  • Left ventricular remodeling post myocardial infarction
    Takayoshi Tsutamoto, Minoru Horie, Masaru Hayashi
    Nippon rinsho. Japanese journal of clinical medicine 63 Suppl 3 323-329 2005年01月
  • In situ Ca2+dynamics of Purkinje fibers and its interconnection with subjacent ventricular myocytes
    Tetsu Hamamoto, Tetsu Hamamoto, Hideo Tanaka, Hiroki Mani, Takuji Tanabe, Katsuji Fujiwara, Takuo Nakagami, Minoru Horie, Masahito Oyamada, Tetsuro Takamatsu
    Journal of Molecular and Cellular Cardiology 38 561-569 2005年01月
    Purkinje fibers play essential roles in impulse propagation to the ventricles, and their functional impairment can become arrhythmogenic. However, little is known about precise spatiotemporal pattern(s) of interconnection between Purkinje-fiber network and the underlying ventricular myocardium within the heart. To address this issue, we simultaneously visualized intracellular Ca 2+ dynamics at Purkinje fibers and subjacent ventricular myocytes in Langendorff-perfused rat hearts using multi-pinhole type, rapid-scanning confocal microscopy. Under recording of electrocardiogram at room temperature spatiotemporal changes in fluo3-fluorescence intensity were visualized on the subendocardial region of the right-ventricular septum. Staining of the heart with either fluo3, acetylthiocholine iodide (ATCHI), or di-4-ANEPPS revealed characteristic structures of Purkinje fibers. During sinus rhythm (about 60 bpm) or atrial pacing (up to 3 Hz) each Purkinje-fiber exhibited spatiotemporally synchronous Ca 2+ transients nearly simultaneously to ventricular excitation. Ca 2+ transients in individual fibers were still synchronized within the Purkinje-fiber network not only under high-K + (8 mM) perfusion-induced Purkinje-to-ventricular (P-V) conduction delay, but also under unidirectional, orthodromic P-V block produced by 10-mM K + perfusion. While spontaneous, asynchronous intracellular Ca 2+ waves were identified in injured fibers of Purkinje network locally, surrounding fibers still exhibited Ca 2+ transients synchronously to ventricular excitation. In summary, these results are the first demonstration of intracellular Ca 2+ dynamics in the Purkinje-fiber network in situ. The synchronous Ca 2+ transients, preserved even under P-V conduction disturbances or under emergence of Ca 2+ waves, imply a syncytial role of Purkinje fibers as a specialized conduction system, whereas unidirectional block at P-V junctions indicates a substrate for reentrant arrhythmias. © 2005 Elsevier Ltd. All rights reserved.
  • Torasemide inhibits transcardiac extraction of aldosterone in patients with congestive heart failure [3]
    Takayoshi Tsutamoto, Hiroshi Sakai, Atsuyuki Wada, Chitose Ishikawa, Keijin Ohno, Masanori Fujii, Takashi Yamamoto, Tomoyuki Takayama, Tomohiro Dohke, Minoru Horie
    Journal of the American College of Cardiology 44 2252-2253 2004年12月
  • Evaluation of cardiac resynchronization therapy in drug-resistant idiopathic dilated cardiomyopathy by means of technetium-99m tetrofosmin electrocardiography-gated single-photon emission computed tomography
    Shinro Matsuo, Tetsuya Matsumoto, Ichiro Nakae, Makoto Ito, Yasuyuki Nakamura, Masahiko Takada, Kiyoshi Murata, Minoru Horie
    Experimental and Clinical Cardiology 9 248-250 2004年12月
    The present case report describes a 72-year-old woman with drug-resistant heart failure. Cardiac resynchronization therapy was performed. Cardiac function was evaluated using a quantitative gated single-photon emission computed tomography (QGS) program with technetium-99m tetrofosmin. During atrial-right ventricular pacing, the left ventricular ejection fraction (LVEF) was 28%, end diastolic volume (EDV) was 141 mL and end systolic volume (ESV) was 101 mL. LVEF was 31%, EDV was 142 mL and ESV was 98 mL during dual chamber pacing. During atrial-left ventricular pacing, LVEF, EDV and ESV were 32%, 18 mL and 100 mL, respectively. Diastolic function was evaluated using Vcdiff software (Daiichi Radioisotope Laboratories Ltd, Japan). Cardiac resynchronization therapy may improve cardiac function, which was evaluated accurately and non-invasively by electrocardiography-gated single-photon emission computed tomography. © 2004 Pulsus Group Inc. All rights reserved.
  • Endogenous bradykinin suppresses myocardial fibrosis through the cardiac-generated endothelin system under chronic angiotensin-converting enzyme inhibition in heart failure
    Masanori Fujii, Atsuyuki Wada, Atsuyuki Wada, Masato Ohnishi, Takayoshi Tsutamoto, Takehiro Matsumoto, Takashi Yamamoto, Tomoyuki Takayama, Tomohiro Dohke, Takahiro Isono, Yutaka Eguchi, Minoru Horie
    Journal of Cardiovascular Pharmacology 44 2004年11月
    In congestive heart failure, angiotensin-converting enzyme inhibitors (ACEIs) may prevent cardiac fibrosis via interaction with both angiotensin II and endothelin-1, which enhance myocardial collagen synthesis. However, whether endogenous bradykinin with an ACEI modifies the cardiac collagen architecture, affecting the endothelin system, has not yet been fully elucidated. We evaluated the changes in circulating hormonal factors, myocardial fibrosis and cardiac gene expression closely linked with heart failure, using an orally active specific bradykinin type 2 receptor antagonist, FR173657 (0.3 mg/kg/day, n = 6), with an ACEI, enalapril (1 mg/kg/day), in dogs with tachycardia-induced congestive heart failure (270 p.p.m., 22 days) and compared the effects with enalapril alone (n = 6). Although there were no differences observed in blood pressure, plasma renin activity, aldosterone and endothelin-1 levels, combined FR173657 significantly increased the cardiac expression of preproendothelin-1 mRNA (P < 0.05) and collagen type I and type III mRNA (P < 0.05), and cardiac collagen deposits (P < 0.05), and decreased eNOS gene expression (P < 0.05) in the left ventricle compared with the ACEI-treated group. Furthermore, there was a significant negative correlation between the expression of preproendothelin-1 and eNOS mRNA levels (r = -0.708, P < 0.001). In conclusion, bradykinin may prevent cardiac fibrosis in part via suppression of the local endothelin system in the failing heart through the enhancement of nitric oxide production under chronic angiotensin-converting enzyme inhibition.
  • Long-term treatment with a phosphodiesterase type 5 inhibitor improves pulmonary hypertension secondary to heart failure through enhancing the natriuretic peptides-cGMP pathway
    Takashi Yamamoto, Atsuyuki Wada, Atsuyuki Wada, Takayoshi Tsutamoto, Masato Ohnishi, Minoru Horie
    Journal of Cardiovascular Pharmacology 44 596-600 2004年11月
    In advanced heart failure (HF), the compensatory pulmonary vasodilation is attenuated due to the relative insufficiency of cGMP despite increased secretion of natriuretic peptides (NPs). Phosphodiesterase type 5 (PDE5) inhibitors prevent cGMP degradation, and thus may potentiate the effect of the NPs-cGMP pathway. We orally administered a specific PDE5 inhibitor, T-1032 (1 mg/kg; twice a day, n = 7) or placebo (n = 7) for 2 weeks in dogs with HF induced by rapid pacing (270 bpm, 3 weeks) and examined the plasma levels of atrial natriuretic peptide (ANP), cGMP, and hemodynamic parameters. We also examined the hemodynamic changes after injection of a specific NPs receptor antagonist, HS-142-1 (3 mg/kg), under treatment with T-1032. T-1032 significantly increased plasma cGMP levels compared with the vehicle group despite low plasma ANP levels associated with improvement in cardiopulmonary hemodynamics. HS-142-1 significantly decreased plasma cGMP levels in both groups, whereas it did not change all hemodynamic parameters in the vehicle group. In contrast, in the T-1032 group, HS-142-1 significantly increased pulmonary arterial pressure and pulmonary vascular resistance. These results indicated that long-term treatment with a PDE5 inhibitor improved pulmonary hypertension secondary to HF and the NPs-cGMP pathway contributed to this therapeutic effect.
  • Contribution of vascular NAD(P)H oxidase to endothelial dysfunction in heart failure and the therapeutic effects of HMG-CoA reductase inhibitor
    Tomoyuki Takayama, Atsuyuki Wada, Atsuyuki Wada, Takayoshi Tsutamoto, Masato Ohnishi, Masanori Fujii, Takahiro Isono, Minoru Horie
    Circulation Journal 68 1067-1075 2004年11月
    Background: The vascular NAD(P)H oxidase-derived superoxide anion (O 2 -) plays a crucial role in the pathological progression of hypertension and atherosclerosis, and HMG-CoA reductase inhibitors (statins) have vascular antioxidant effects. However, it is unclear whether the vascular NAD(P)H oxidase is involved in the endothelial dysfunction of congestive heart failure (CHF) and whether HMG-CoA reductase inhibitors (statins) exert their vasoprotective effects in CHF. The present study examined both the involvement of vascular NAD(P)H oxidase in endothelial dysfunction in dogs with tachycardia-induced CHF and the therapeutic effect of a statin (pitavastatin). Methods and Results: Femoral blood flow (FBF) responses to acetylcholine was significantly impaired in the CHF group, but were improved by pitavastatin. Vascular O 2 - production, NAD(P)H oxidase activity and Nox4 and p47phox expression were significantly elevated in CHF compared with the normal group. The elevated O 2 -production in the CHF group was suppressed by the NAD(P)H oxidase inhibitor, apocynin, to the normal level. In contrast, neither the gene expression nor the activity of endothelial nitric oxide synthase (eNOS) differed significantly between the normal and CHF groups. However, pitavastatin significantly suppressed O 2 - production, NAD(P)H oxidase activity and Nox4 and p47phox expression and increased eNOS expression and activity compared with the CHF group. Conclusions: The activated vascular NAD(P)H oxidase contributes to endothelial dysfunction in CHF, which was partly improved by pitavastatin via its inhibition of NAD(P)H oxidase.
  • Antihypertensive therapy of morning blood pressure - ATOM study
    Shinji Tamaki, Masato Ohnishi, Minoru Horie, Satoshi Morimoto
    Japanese Pharmacology and Therapeutics 32 481-486 2004年10月
    Background: Several prospective studies have indicated that early morning hypertension and morning blood pressure (BP) surge are important risk factors of stroke or cardiovascular events. We investigated differences between early morning and clinic BP as well as morning BP surge in patients being treated for essential hypertension. Design: We recorded systolic BP at three different times 1) before going to bed and, 2) in the early morning period before visiting the clinic by self-measurement at home, and 3) while at the clinic. Results: Although 40.4% of all patients demonstrated normal systolic BP while at the clinic, 50.3% of those demonstrated early morning hypertension. Only 19.0% of the patients demonstrated normal systolic BP both at the clinic and in the early morning. The mean morning BP surge was 9.16 ± 16.9 mmHg. Those patients who had taken valsartan resulted a particularly large surge, and a significant difference was observed between candesartan. Conclusion: These findings suggest that a strategy for controlling BP must be considered not only clinic BP but also morning home BP, and that the duration of BP lowering effects varies between anti-hypertensive agents.
  • Detection of metabolic abnormality in asynergic regions of ischemic human myocardium using 31P and 1H magnetic resonance spectroscopy
    Ichiro Nakae, Kenichi Mitsunami, Kenichi Mitsunami, Takahiro Yabe, Toshiro Inubushi, Shigehiro Morikawa, Shinro Matsuo, Terue Koh, Minoru Horie
    Journal of Cardiovascular Magnetic Resonance 6 685-696 2004年08月
    To assess quantitatively phosphocreatine (PCr), adenosine triphosphate (ATP) and total creatine (CR) in asynergic regions of ischemic human myocardium using phosphorus ( 31 P) and proton magnetic resonance spectroscopy ( 1 H MRS). Patients were divided into two groups: 31 P MRS and 1 H MRS. In each group, patients were subdivided into three groups using echocardiography: a normokinetic [WNP (n = 6) in 31 P MRS, WNH (n = 10) in 1 H MRS], a hypokinetic [WHP (n = 13), WHH (n = 7)] , and a- or dyskinetic wall motion groups [WAP (n = 14), WAH (n = 6)]. They were compared with normal subjects of each group [CNP (n = 10), CNH (n = 10)] . 31 P MRS spectra were obtained from the anterior and apical regions of the left ventricle by slice-selected 1D CSI. 1 H MRS spectra were obtained from the 2 x 2 x 2-cm voxel set in the left ventricular wall by the PRESS method. In the 31 P MRS group, myocardial PCr was significantly lower in the WHP and WAP groups than in the CNP group, but myocardial PCr in the WNP group did not differ from that in CNP. A difference in ATP could not be detected among the four groups. In the 1 H MRS group, myocardial CR was significantly lower in the WHH and WA. groups than in the CNH group. Myocardial CR in the WNH group did not differ from that in the CNH. The noninvasive 31 P and 1 H MRS approach is useful in the assessment of metabolite reduction associated with wall motion abnormality.
  • The relationship between flow-mediated brachial artery vasodilation and coronary vasomotor responses to bradykinin: Comparison with those to acetylcholine
    Shinro Matsuo, Tetsuya Matsumoto, Hiroyuki Takashima, Naoto Ohira, Tetsunobu Yamane, Yo Yasuda, Yasuhiro Tarutani, Minoru Horie
    Journal of Cardiovascular Pharmacology 44 164-170 2004年08月
    Flow-mediated dilation (FMD) of brachial artery provides a noninvasive assessment of coronary endothelial dysfunction. Acetylcholine (ACh) has been used as an agent for estimating coronary endothelial function. In contrast to ACh, there is no evidence for a relationship between FMD and coronary vasodilation to bradykinin (BK). The aim of this study was to compare the flow-mediated vasodilation of brachial artery with coronary vasomotor responses to intracoronary ACh or BK in patients with an angiographically normal left anterior descending coronary artery. Ninety-one patients underwent the cardiac catheterization examination with coronary endothelial function testing and the brachial ultrasound study. BK (0.2, 0.6, 2.0 μg/min) and ACh (3, 10, 30 μg/min) were administered into the left coronary artery in a stepwise manner. Coronary blood flow was evaluated by the Doppler flow velocity measurement. Coronary diameters were measured by the quantitative coronary angiography. The assessment of endothelial function in the brachial artery was made in response to reactive hyperemia with high-resolution ultrasound. Bradykinin induced dose-dependent increases in epicardial coronary diameter and blood flow. There was a significant positive correlation between FMD- and BK-induced vasodilations of epicardial coronary arteries (0.2 μg/min: r = 0.30; 0.6 μg/min: r = 0.42; 2.0 μg/min: r = 0.44, P < 0.01, respectively) and resistance coronary arteries (0.2 μg/min: r = 0.40; 0.6 μg/min: r = 0.56; 2.0 μg/min: r = 0.59, P < 0.0001, respectively). FMD correlated with ACh-induced vasomotions of resistance but not epicardial coronary arteries. No correlation was seen between nitroglycerin-induced brachial artery vasodilation and BK-induced coronary vasodilation. The endothelial dysfunction of peripheral arteries correlated well with that of the coronary arteries especially vasomotor responses to BK.
  • Plasma level of oxidized low-density lipoprotein is an independent determinant of coronary macrovasomotor and microvasomotor responses induced by bradykinin
    Tetsuya Matsumoto, Tetsuya Matsumoto, Hiroyuki Takashima, Naoto Ohira, Yasuhiro Tarutani, Yo Yasuda, Tetsunobu Yamane, Shinro Matsuo, Minoru Horie
    Journal of the American College of Cardiology 44 451-457 2004年07月
    Objectives We examined the relationship between coronary endothelium-dependent vasodilation in response to bradykinin (BK) and plasma levels of oxidized low-density lipoprotein (oxLDL) in subjects with normal coronary arteries. Background It is unclear whether the plasma oxLDL level is a determinant of coronary endothelial function. Bradykinin plays an important role in regulating resting coronary tone and flow-mediated coronary vasomotion. Methods Coronary blood flow (CBF) in the left anterior descending (LAD) coronary artery was assessed by quantitative angiography and a Doppler flow wire in 94 consecutive subjects with normal coronary arteries. The plasma oxLDL level was measured by enzyme-linked immunosorbent assay using DLH3R, a specific antibody against oxLDL. Results Plasma levels of oxLDL in diabetic subjects (n = 13) were higher than those in non-diabetic subjects (n = 81). Plasma levels of oxLDL correlated with body mass index (BMI). Bradykinin at doses of 0.2, 0.6, and 2.0 μg/min caused dose-dependent increases in diameter and CBF in the LAD coronary artery. By a univariate analysis, oxLDL levels significantly correlated with epicardial (r = -0.30, p < 0.0001) and resistant (r = -0.36, p = 0.003) coronary vasodilator responses to BK at 2.0 μg/min, whereas total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were not associated with these coronary responses. In a stepwise multivariate analysis, oxLDL levels were significantly correlated with epicardial and resistant coronary vasomotor responses to BK, independent of age, gender, smoking status, other lipid levels, BMI, hypertension, and diabetes. Conclusions The plasma level of oxLDL is an appropriate surrogate for assessing coronary endothelial-dependent vasomotor function as estimated by responses to BK compared with conventional risk factors for atherosclerosis. © 2004 by the American College of Cardiology Foundation.
  • Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome: Multicenter study in Japan
    Wataru Shimizu, Wataru Shimizu, Wataru Shimizu, Minoru Horie, Seiko Ohno, Kotoe Takenaka, Masato Yamaguchi, Masami Shimizu, Takashi Washizuka, Yoshifusa Aizawa, Kazufumi Nakamura, Tohru Ohe, Takeshi Aiba, Yoshihiro Miyamoto, Yasunao Yoshimasa, Jeffrey A. Towbin, Silvia G. Priori, Shiro Kamakura
    Journal of the American College of Cardiology 44 117-125 2004年07月
    Objectives We sought to compare the arrhythmic risk and sensitivity to sympathetic stimulation of mutations located in transmembrane regions and C-terminal regions of the KCNQ1 channel in the LQT1 form of congenital long QT syndrome (LQTS). Background The LQT1 syndrome is frequently manifested with variable expressivity and incomplete penetrance and is much more sensitive to sympathetic stimulation than the other forms. Methods Sixty-six LQT1 patients (27 families) with a total of 19 transmembrane mutations and 29 patients (10 families) with 8 C-terminal mutations were enrolled from five Japanese institutes. Results Patients with transmembrane mutations were more frequently affected based on electrocardiographic (ECG) diagnostic criteria (82% vs. 24%, p < 0.0001) and had more frequent LQTS-related cardiac events (all cardiac events: 55% vs. 21%, p = 0.002; syncope: 55% vs. 21%, p = 0.002; aborted cardiac arrest or unexpected sudden cardiac death: 15% vs. 0%, p = 0.03) than those with C-terminal mutations. Patients with transmembrane mutations had a greater risk of first cardiac events occurring at an earlier age, with a hazard ratio of 3.4 (p = 0.006) and with an 8% increase in risk per 10-ms increase in corrected Q-Tend. The baseline ECG parameters, including Q-Tend, Q-Tpeak, and Tpeak-end intervals, were significantly greater in patients with transmembrane mutations than in those with C-terminal mutations (p < 0.005). Moreover, the corrected Q-Tend and Tpeak-end were more prominently increased with exercise in patient s with transmembrane mutations (p < 0.005). Conclusions In this multicenter Japanese population, LQT1 patients with transmembrane mutations are at higher risk of congenital LQTS-related cardiac events and have greater sensitivity to sympathetic stimulation, as compared with patients with C-terminal mutations. © 2004 by the American College of Cardiology Foundation.
  • Brain Natriuretic Peptide
    蔦本 尚慶, 堀江 稔
    臨床病理 52(8) 655-668 2004年08月
  • 164)救急隊による心肺蘇生と病病連携にて社会復帰しえたマラソン競技中の心肺停止の一例(第102回日本循環器学会近畿地方会)
    浜本 徹, 辻田 靖之, 江口 豊, 寺村 真範, 芦原 貴司, 伊藤 誠, 堀江 稔, 松本 祐一, 川嶋 剛史
    Circulation journal : official journal of the Japanese Circulation Society 71(0) 2007年04月
  • Scintigraphic evaluation of cardiac metabolism in multicentric Castleman's disease
    Shinro Matsuo, Yasuyuki Nakamura, Ichiro Nakae, Tetsuya Matsumoto, Masahiko Takada, Kiyoshi Murata, Minoru Horie
    Internal Medicine 43 490-492 2004年06月
    A 72-year-old woman had insidious onset of heart failure, and was diagnosed as multicentric Castleman's disease. She underwent myocardial imaging with technetium-99m tetrofosmin, I-123 beta-methyl-iodophenyl pentadecanoic acid (BMIPP). Technetium-99m tetrofosmin studies showed almost normal uptake of the left ventricular myocardium indicating normal myocardial perfusion. I-123 BMIPP showed reduced uptake in the apical segment of the myocardium, indicating regional fatty acid metabolic abnormalities.
  • 血液生化学検査 BNP濃度測定の意義--重症度評価,病態把握,治療効果判定 (心不全(上)最新の基礎・臨床研究の進歩) -- (診断学・検査の進歩)
    蔦本 尚慶, 堀江 稔
    日本臨床 65(0) 417-425 2007年04月
  • 抗アルドステロン薬の有用性
    蔦本 尚慶, 林 優, 石川 千登世, 前田 圭子, 酒井 宏, 大野 慶人, 和田 厚幸, 堀江 稔
    循環制御 25(1) 10-17 2004年03月
  • リモデリングの予防と改善は可能か
    堀江 稔
    日本内科学会雑誌 96 2007年02月
  • かかりつけ医と心不全 慢性心不全の検査 (特集 かかりつけ医が診る心不全)
    蔦本 尚慶, 堀江 稔
    クリニカルプラクティス 26(1) 16-23 2007年01月
  • 薬剤性QT延長症候群 (特集 精神料病院で気をつけるべき身体合併症)
    西尾 由貴子, 堀江 稔
    日本精神科病院協会雑誌 26(7) 681-684 2007年
  • 心筋マーカー
    最新医学 別冊 循環器7 58-67 2007年
  • 慢性心不全の検査
    クリニカルプラクティス 26(1) 16-23 2007年
  • Brugada症候群とLQT3のオーバーラップ:SCN5A変異の臨床的特徴と分子メカニズム
    Jornal of Cardiology 50 132-132 2007年
  • アディポネクチンと心不全予後-BMIによる検討
    Journal of Cardiology 50 337-337 2007年
  • アトルバスタチンは非虚血性心不全患者の心臓交感神経活性を改善する
    Journal of Cardiology 50 431-431 2007年
  • 冠血管機能の性差:冠攣縮性狭心症と胸痛症候群の検討
    Journal of Cardiology 50 137-137 2007年
  • 心筋マーカー
    急性冠症候群 58-67 2007年
  • ANPとBNPを病態診断にいかす
    新心臓病診療プラクチイス 68-72 2007年
  • 冠血管機能の性差:冠攣縮性狭心症と胸痛症候群の検討
    第55回日本心臓病学会学術集会 2007年
  • Brugada症候群とLQT3のオーバーラップ:SCN5A変異の臨床的特徴と分子メカニズム
    第55回日本心臓病学会学術集会 2007年
  • アディポネクチンと心不全予後-BMIによる検討
    第55回日本心臓病学会学術集会 2007年
  • アトルバスタチンは非虚血性心不全患者の心臓交感神経活性を改善する
    第55回日本心臓病学会学術集会 2007年
  • 心不全患者におけるBNPとNT-proBNP分泌動態の比較
    第55回日本心臓病学会学術集会 2007年
  • 高分子アデイポネクチンは心不全予後の指標として有用か?
    第55回 日本心臓病学会学術集会 2007年
  • バイオマカーとしてのナトリウム利尿ペプチド(BNP, N端-proBNP)と腎機能
    最新医学 62(9) 141(1967)-147(1973) 2007年
  • Transcardiac increase in tumor necrosis factor-α and left ventricular end-diastolic volume in patients with dilated cardiomyopathy
    Takayoshi Tsutamoto, Atsuyuki Wada, Masato Ohnishi, Takashi Tsutsui, Chitose Ishii, Keijin Ohno, Masanori Fujii, Takehiro Matsumoto, Takashi Yamamoto, Tomoyuki Takayama, Tomohiro Dohke, Minoru Horie
    European Journal of Heart Failure 6 173-180 2004年03月
    Background: It remains unclear whether tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) are secreted from the failing heart and whether there is a relationship between the transcardiac gradients of these cytokines and left ventricular (LV) remodeling. Aims: This study evaluated the relationship between transcardiac gradients of cytokines and LV volume and function in congestive heart failure patients with dilated cardiomyopathy (DCM). Methods and results: We measured the plasma levels of TNF-α and IL-6 in the aortic root (Ao) and the coronary sinus (CS) in 60 patients with DCM. There was no difference in plasma IL-6 between the Ao and the CS. However, the plasma TNF-α level was significantly higher in the CS than that in the Ao. There was a significant correlation between the transcardiac gradient of plasma TNF-α and the LV end-diastolic volume index (LVEDVI) and LV ejection fraction. According to stepwise multivariate analyses, the transcardiac increase of TNF-α showed an independent and significantly positive relationship with a large LVEDVI. Conclusions: These results indicate that the elevated plasma TNF-α is partly derived from the failing heart in patients with DCM and that TNF-α plays a potential role in structural LV remodeling in patients with DCM. © 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
  • Which heart failure patients would benefit to evaluated plasma adiponectin for predicting mortality risk in Japan.
    第11回日本心不全学会 2007年
  • Angiotensin-converting enzyme insertion/deletion polymorphism modulates coronary release of tissue plasminogen activator in response to bradykinin
    Naoto Ohira, Tetsuya Matsumoto, Shinji Tamaki, Hiroyuki Takashima, Yasuhiro Tarutani, Tetsunobu Yamane, Yo Yasuda, Minoru Horie
    Hypertension Research 27 39-45 2004年01月
    The aim of this study was to assess the relationship between the angiotensin converting enzyme gene (ACE) genotype and endothelium-dependent coronary vasomotor and fibrinolytic activity. The ACE DD genotype has been reported to be a risk factor for myocardial infarction. However, the mechanism is unknown. The fibrinolytic and renin-angiotensin systems are linked via ACE at the vascular beds. We studied 73 patients (II: n=24; ID: n=37; DD: n=12) who underwent diagnostic cardiac catheterization. Graded doses of bradykinin (BK) (0.2, 0.6, 2.0 μg/min) and acetylcholine (30,100 μg/min) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by measuring Doppler flow velocity. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS). Coronary release of tPA antigen was determined as a CS-Ao gradient×CBF×[(100-hematocrit) / 100]. ACE genotypes were determined using polymerase chain reaction. The ACE genotype did not appear to affect coronary macro- and microvascular responses induced by BK or acetylcholine. Coronary tissue plasminogen activator (tPA) release induced by BK was depressed in subjects with the ACE DD genotype. ACE levels in the DD genotype were significantly higher than those in the ID or II genotype. In all of the subjects, there was a significant negative correlation between the serum level of ACE activity and net coronary tPA release in response to BK at 0.6 μg/min. In conclusions, the DD genotype of the ACE gene impairs the coronary release of tPA induced by BK.
  • Renin may have an important role in cardio-renal interaction in patients with heart failure
    第11回日本心不全学会 2007年
  • Alpha-adducin gene and hypertension
    Shinji Tamaki, Yasuyuki Nakamura, Minoru Horie, Masahiko Kinoshita, Naoharu Iwai
    Nippon rinsho. Japanese journal of clinical medicine 62 Suppl 3 108-111 2004年01月
  • 心房リモデリングの予防と改善は可能か
    第104回 日本内科学会 2007年
  • Arrhythmias and natriuretic polypeptides
    Minoru Horie
    Nippon rinsho. Japanese journal of clinical medicine 62 Suppl 9 101-102 2004年01月
  • 心房筋リモデリングを考慮したヒト心房細動in silicoモデルにおけるアミオダロンの急性効果と慢性効果
    第12回アミオダロン研究会 2007年
  • Brain natriuretic peptide
    Takayoshi Tsutamoto, Minoru Horie
    Rinsho byori. The Japanese journal of clinical pathology 52 655-668 2004年01月
    Plasma levels of various neurohumoral factors are activated and have an important role of the pathophysiology of congestive heart failure (CHF). Atrial natriuretic peptide (ANP) and brain (or B-type) natriuretic peptide (BNP) are secreted from cardiomyocytes in response to atrial or ventricular wall stretch. The natriuretic peptides have a fundamental role in cardiovascular remodeling, volume homeostasis, and the response to myocardial injury. Clinical investigations of these peptides have focused on their diagnostic usefulness for heart failure and left ventricular dysfunction and their prognostic usefulness after acute coronary syndromes and heart failure. In patients with left ventricular systolic dysfunction, a high plasma BNP level is an independent prognostic predictor of CHF patients, suggesting that the compensatory activity of the cardiac natriuretic peptide system is attenuated as mortality increases in chronic CHF patients with high plasma levels of ANP and BNP. BNP is more useful than ANP for diagnosis and management of CHF. Recently, rapid BNP assay is available in our country, rapid measurement of BNP in the emergency department may improve the evaluation and treatment of patients with acute dyspnea and thereby reduced the time to discharge and the total cost of treatment. In addition, BNP-guided treatment of heart failure may reduce total cardiovascular events, and delayed time to first event combination with intensive clinically guided treatment.
  • Insulinotropic action of glutamate is dependent on the inhibition of ATP-sensitive potassium channel activities in MIN 6 β cells
    Hidenori Katsuta, Sachihiko Ozawa, Tomonori Ninomiya, Tatsuhiro Shimoyama, Eisuke Ito, Toshiaki Tanaka, Shinya Yamaguchi, Hiroshi Katahira, Shinya Nagamatsu, Minoru Horie, Minoru Horie, Hitoshi Ishida
    Biochemical and Biophysical Research Communications 311 660-664 2003年11月
    To investigate the cellular mechanism of insulinotropic effect of glutamate in pancreatic β cells, we utilized patch-clamp technique to monitor directly the activities of ATP-sensitive potassium channels (K ATP channels). Dimethylglutamate (5mM), a membrane-permeable analog of glutamate, augmented the insulin release induced by the stimulatory concentrations of glucose (p < 0.05-0.01). In the cell-attached configurations, dimethylglutamate reversibly and significantly suppressed the K ATP channel activities (p < 0.01). On the other hand, no significant effect was observed when glutamate itself was applied to the inside-out patches, whereas the prompt and reversible sup pression was recorded in the case of ATP (p < 0.01). These results indicate that the insulinotropic action of glutamate in β cells could be derived from the inhibition of K ATP channel activities, probably due to generation of messengers via intracellular metabolism such as ATP. © 2003 Elsevier Inc. All rights reserved.
  • Proton Magnetic Resonance Spectroscopy can Detect Creatine Depletion Associated with the Progression of Heart Failure in Cardiomyopathy
    Ichiro Nakae, Kenichi Mitsunami, Kenichi Mitsunami, Tomoko Omura, Takahiro Yabe, Takayoshi Tsutamoto, Shinro Matsuo, Masayuki Takahashi, Shigehiro Morikawa, Toshiro Inubushi, Yasuyuki Nakamura, Masahiko Kinoshita, Minoru Horie
    Journal of the American College of Cardiology 42 1587-1593 2003年11月
    OBJECTIVES: This study noninvasively examined total creatine (CR) of the myocardium in dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) using proton magnetic resonance spectroscopy ( 1 H-MRS). BACKGROUND: Abnormalities in CR metabolism in failing hearts have been reported. A biochemical study suggested that myocardial metabolic changes are very similar in DCM and HCM despite the different heart failure (HF) mechanisms. METHODS: Using cardiac-gated 1 H-MRS with magnetic resonance image (MRI) -guided point-resolved spectroscopy (PRESS) localization, we quantitatively measured septal CR. Patients with either DCM (n = 11) or HCM (n = 7) and age-matched normal subjects (n = 14) were examined. RESULTS: Myocardial CR was significantly lower in DCM patients (16.1 ± 4.5 μmol/g wet weight [range 10.2 to 22.9], p < 0.05) than that in subjects with normal hearts (27.6 ± 4.1 μmol/g [range 21.4 to 36.2]). Myocardial CR in HCM patients (22.6 ± 8.1 μmol/g [range 12.2 to 34.5] ) was significantly lower than that in subjects with normal hearts (p < 0.05) but was significantly higher than that in DCM patients (p < 0.05). In 18 patients with either DCM or HCM, myocardial CR correlated positively with left ventricular ejection fraction (LVEF) (y = 0.22x + 9.8, r = 0.73, p = 0.0006) but correlated negatively with plasma B-type natriuretic peptide (BNP) levels (y = -0.012x + 22.4, r = -0.54, p = 0.022). CONCLUSIONS: This study showed that 1 H-MRS can noninvasively detect CR depletion associated with the severity of HF in cardiomyopathy. © 2003 by the American College of Cardiology Foundation.
  • Genetic background predisposing the drug-induced long QT syndrome
    Minoru Horie
    Folia Pharmacologica Japonica 121 401-407 2003年06月
    Molecular and cellular mechanisms underlying the QT prolongation have been elucidated largely because of the recent understanding of the generation of the congenital forms of QT prolongation; i.e., the long QT syndrome. To date, at least 7 different genes that modulate cardiac ion channels were identitied to be associated with the syndrome. In the clinical setting, the drug-induced long QT syndrome is more frequently seen and therefore important. We found several mutations as well as an SNP specific among the Japanese population in probands referred to as the secondary long QT patients, including the drug-induced cases. These findings raised the potential that there are also predisposing risk factors at patient's side.
  • Immediate administration of mineralocorticoid receptor antagonist spironolactone prevents post-infarct left ventricular remodeling associated with suppression of a marker of myocardial collagen synthesis in patients with first anterior acute myocardial in
    Masaru Hayashi, Takayoshi Tsutamoto, Atsuyuki Wada, Takashi Tsutsui, Chitose Ishii, Keijin Ohno, Masanori Fujii, Atsushi Taniguchi, Tomokazu Hamatani, Yoshitaka Nozato, Ken Kataoka, Naoki Morigami, Masato Ohnishi, Masahiko Kinoshita, Minoru Horie
    Circulation 107 2559-2565 2003年05月
    Background - Aldosterone (ALD) has been shown to stimulate cardiac collagen synthesis and fibroblast proliferation via activation of local mineralocorticoid receptors. In patients with acute myocardial infarction, we demonstrated that ALD was extracted through the infarct heart and extracting ALD-stimulated post-infarct left ventricular (LV) remodeling. Methods and Results - To evaluate the effect of mineralocorticoid receptor antagonist (MRA) spironolactone on post-infarct LV remodeling, 134 patients with first anterior acute myocardial infarction were randomly divided into the MRA (n=65) or non-MRA (n=69) groups after revascularization. All patients were administered angiotensin-converting enzyme (ACE) inhibitor and study drug just after revascularization. Left ventriculography with contrast medium was performed at the acute stage and after 1 month to evaluate LV remodeling. ALD was measured at aortic root and coronary sinus. There was no difference in the baseline characteristics including infarct size and LV performance between the two groups. However, LV ejection fraction was significantly improved in the MRA group compared with that in the non-MRA group (46.0±0.6% to 53.2±0.8% versus 46.5±0.8% to 51.0±0.8%, P interaction =0.012). LV end-diastolic volume index was significantly suppressed in the MRA group compared with that in non-MRA group (86.5±1.0 to 90.6±2.4 versus 87.5±1.3 to 106.8±3.5 mL/m 2 , P interaction =0.002). Transcardiac extraction of ALD through the heart was significantly suppressed in the MRA group (P interaction =0.001), and plasma procollagen type III aminoterminal peptide level, a biochemical marker of fibrosis, was significant lower in the MRA group compared with the non-MRA group (P interaction =0.002). Conclusions - These findings indicate that MRA combined with ACE inhibitor can prevent post-infarct LV remodeling better than ACE inhibitor alone in association with the suppression of a marker of collagen synthesis.
  • 第13回体表心臓微小電位研究会 シンポジウム LQT症候群の病態診断における心電学的アプローチ―VT発生との関連について― 遺伝性QT延長症候群(LQTS)の遺伝子型による心電図学的特徴:LQT1とLQT2における,T波形および再分極指標の運動による変化
    竹中 琴重, 藍 智彦, 小堀 敦志, 二宮 智紀, 大谷 秀夫, 久保田 友之, 堀江 稔, 清水 渉, 高木 洋, 鎌倉 史郎
    心臓 36(1) 32-32 2004年
  • Plasma brain natriuretic peptide as a useful biochemical marker of congestive heart failure
    Takayoshi Tsutamoto, Minoru Horie
    Nippon rinsho. Japanese journal of clinical medicine 61 782-788 2003年01月
    Neurohumoral factors, which is divided to two groups, are activated in patients with congestive heart failure(CHF). One is cardiotoxic biochemical markers such as nor-epinephrine, angiotensin II, endothelin-1, and vasopressin, the other is cardioprotective biochemical markers such as atrial natriuretic peptide, and brain natriuretic peptide (BNP). Among various neurohumoral factors, plasma level of BNP is the most useful marker to diagnose and evaluate the severity and prognosis of CHF patients. The reason why the usefulness of plasma BNP is 1) BNP is of ventricular origin, 2) BNP reflects hemodynamic abnormalities(high left ventricular end-diastolic pressure and/or low left ventricular ejection fraction), 3) Attenuation of biological compensation of beneficial effects of BNP(vasodilation, diuresis) in advanced-staged CHF.
  • Angiotensin-converting enzyme inhibition but not angiotensin II type 1 receptor antagonism augments coronary release of tissue plasminogen activator in hypertensive patients
    Tetsuya Matsumoto, Tetsuya Matsumoto, Kazuo Minai, Hajime Horie, Naoto Ohira, Hiroyuki Takashima, Yasuhiro Tarutani, Yo Yasuda, Tomoya Ozawa, Shinro Matsuo, Masahiko Kinoshita, Minoru Horie
    Journal of the American College of Cardiology 41 1373-1379 2003年01月
    OBJECTIVES: We compared the effects of perindopril and losartan on endothelium-dependent coronary vasomotor and fibrinolytic function. BACKGROUND: The renin-angiotensin system regulates the vascular fibrinolytic balance. However, the effects of angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists on coronary fibrinolytic function have not been compared in hypertensive patients. METHODS: Forty-five patients with hypertension were randomly assigned to three groups : 16 patients were treated with perindopril (4 mg/day) for four weeks; 15 were treated with losartan (50 mg/day) for four weeks; and 14 were not treated with either perindopril or losartan (control group). Graded doses of bradykinin (BK) (0.2, 0.6, and 2.0 μg/min) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity measurement. RESULTS: Bradykinin induced dose-dependent increases in CBF in all groups. The increases in CBF induced by BK in the perindopril and losartan groups were significantly greater than those in the control group. Net coronary tissue-type plasminogen activator (t-PA) release was enhanced by BK in all groups, and the increase in the perindopril group was greater than that in the losartan and control groups. Bradykinin did not alter plasminogen activator inhibitor type 1 levels in any of the groups. CONCLUSIONS: Perindopril and losartan similarly augment BK-induced coronary vasodilation. Perindopril may have a greater potential to enhance the BK-induced coronary release of t-PA than losartan. © 2003 by the American College of Cardiology Foundation.
  • α1-adrenoceptor-mediated breakdown of phosphatidylinositol 4,5-bisphosphate inhibits pinacidil-activated ATP-sensitive K+ currents in rat ventricular myocytes
    Tetsuya Haruna, Hidetada Yoshida, Tomoe Y. Nakamura, Lai Hua Xie, Hideo Otani, Tomonori Ninomiya, Makoto Takano, William A. Coetzee, Minoru Horie
    Circulation Research 91 232-239 2002年08月
    Phosphatidylinositol 4,5-bisphosphate (PIP 2 ) stimulates ATP-sensitive K + (K ATP ) channel activity. Because phospholipase C (PLC) hydrolyzes membrane-bound PIP 2 , which in turn may potentially decrease K ATP channel activity, we investigated the effects of the α 1 -adrenoceptor-G q -PLC signal transduction axis on pinacidil-activated K ATP channel activity in adult rat and neonatal mouse ventricular myocytes. The α 1 -adrenoceptor agonist methoxamine (MTX) reversibly inhibited the pinacidil-activated K ATP current in a concentration-dependent manner (IC 50 20.9±6.6 μmol/L). This inhibition did not occur when the specific α 1 -adrenoceptor antagonist, prazosin, was present. An involvement of G proteins is suggested by the ability of GDPβS to prevent this response. Blockade of PLC by U-73122 (2 μmol/L) or neomycin (2 mmol/L) attenuated the MTX-induced inhibition of K ATP channel activity. In contrast, the MTX response was unaffected by protein kinase C inhibition or stimulation by H-7 (100 μmol/L) or phorbol 12,13-didecanoate. The MTX-induced inhibition became irreversible in the presence of wortmannin (20 μmol/L), an inhibitor of phosphatidylinositol-4 kinase, which is expected to prevent membrane PIP 2 replenishment. In excised inside-out patch membranes, pinacidil induced a significantly rightward shift of ATP sensitivity of the channel. This phenomenon was reversed by pretreatment of myocytes with MTX. Direct visualization of PIP 2 subcellular distribution using a PLCδ pleckstrin homology domain-green fluorescent protein fusion constructs revealed reversible translocation of green fluorescent protein fluorescence from the membrane to the cytosol after α 1 -adrenoceptor stimulation. Our data demonstrate that α 1 -adrenoceptor stimulation reduces the membrane PIP 2 level, which in turn inhibits pinacidil-activated K ATP channels.
  • Novel KCNJ2 mutation in familial periodic paralysis with ventricular dysrhythmia
    Tomohiko Ai, Yuichiro Fujiwara, Keiko Tsuji, Hideo Otani, Shozo Nakano, Yoshihiro Kubo, Minoru Horie, Minoru Horie
    Circulation 105 2592-2594 2002年06月
    Background - Mutations in the KCNJ2 gene, which codes cardiac and skeletal inward rectifying K + channels (Kir2.1), produce Andersen's syndrome, which is characterized by periodic paralysis, cardiac arrhythmia, and dysmorphic features. Methods and Results - In 3 Japanese family members with periodic paralysis, ventricular arrhythmias, and marked QT prolongation, polymerase chain reaction/single-strand conformation polymorphism/DNA sequencing identified a novel, heterozygous, missense mutation in KCNJ2, Thr192A1a (T192A), which was located in the putative cytoplasmic chain after the second transmembrane region M2. Using the Xenopus oocyte expression system, we found that the T192A mutant was nonfunctional in the homomeric condition. Coinjection with the wild-type gene reduced the current amplitude, showing a weak dominant-negative effect. Conclusions - T192, which is located in the phosphatidylinositol-4,5-bisphosphate binding site and also the region necessary for Kir2.1 multimerization, is a highly conserved amino acid residue among inward-rectifier channels. We suggest that the T192A mutation resulted in the observed electrical phenotype.
  • Gene-specific response of dynamic ventricular repolarization to sympathetic stimulation in LQT1, LQT2 and LQT3 forms of congenital long QT syndrome
    T. Noda, H. Takaki, T. Kurita, K. Suyama, N. Nagaya, A. Taguchi, N. Aihara, S. Kamakura, K. Sunagawa, K. Nakamura, T. Ohe, M. Horie, C. Napolitano, J. A. Towbin, S. G. Priori, Wataru Shimizu, Wataru Shimizu
    European Heart Journal 23 975-983 2002年06月
    Aims: Differences in the sensitivity of the genotype of the congenital long QT syndrome to sympathetic stimulation have been suggested. This study compared the influence of sympathetic stimulation on continuous corrected QT (QTc) intervals between LQT1, LQT2 and LQT3 forms of the congenital long QT syndrome. Methods and Results: We recorded a 12-lead electrocardiogram continuously before and after bolus injection (0·1 μg . kg -1 of epinephrine followed by continuous infusion (0·1 μg · kg -1 min -1 ) in 12 LQT1, 10 LQT2, 6 LQT3, and 13 control patients. The QT intervals and previous RR intervals of all beats were measured semi-automatically, and the QTc intervals of all beats were calculated by Bazett's method. The dynamic response of the RR interval to epinephrine was no different between the four groups. The QTc was prolonged remarkably (477±42 to 631± 59 ms; P < 0·0005, % delta prolongation = + 32%) as the RR was maximally decreased (at peak of epinephrine), and remained prolonged at steady state conditions of epinephrine (556±56 ms; P < 0·0005 vs baseline, + 17%) in LQT1 patients. Epinephrine also prolonged the QTc dramatically (502±23 to 620±39 ms; P < 0·0005, +24%) at peak of epinephrine in LQT2 patients, but this shortened to baseline levels at steady state (531±25 ms; P=ns vs baseline, +6%). The QTc was much less prolonged at peak of epinephrine in LQT3 (478±44 to 532±41ms; P < 0·05, +11%) and controls (394±21 to 456±18 ms; P < 0·0005, +16%) than in LQT1 and LQT2 patients, and shortened to the baseline levels (LQT3; 466±49 ms, -3%, controls; 397±16 ms, +1%; P=ns vs baseline) at steady state. Conclusion: Our data suggest that the dynamic response of ventricular repolarization to sympathetic stimulation differs between LQT1, LQT2 and LQT3 syndromes, and may explain why the trigger of cardiac events differs between the genotypes. © 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.
  • Electrical remodeling of the ventricular myocardium in myocarditis: Studies of rat experimental autoimmune myocarditis
    Junko Saito, Shinichi Niwano, Hiroe Niwano, Takayuki Inomata, Yoshihiro Yumoto, Kazuko Ikeda, Kimiatsu Inuo, Jisho Kojima, Minoru Horie, Tohru Izumi
    Circulation Journal 66 97-103 2002年05月
    The purpose of this study was to evaluate the electrical remodeling of the ventricular myocardium in the experimental autoimmune myocarditis (EAM) model in Lewis rats. EAM was induced by immunization with cardiac myosin. During the active myocarditis phase, the effective refractory period (ERP), the duration of the monophasic action potential (MAPD) was extracted from the left ventricular free wall, and the mRNA levels of Kv1.4, 4.2, 4.3 and L type Ca 2+ channel were determined by RNase protection assays. The inducibility of ventricular arrhythmia was higher in EAM rats than in the control rat, and the direct relationship between the coupling intervals of the premature stimulus and the ventricular arrhythmia in EAM rats. The ERP was prolonged in EAM rats compared with the control group. The MAPDs determined as 20% and 90% repolarization time, were both longer in EAM rats than in the controls. The level of expression of Kv4.2 mRNA was reduced in EAM rats in comparison with the controls, whereas those of Kv1.4, 4.3 and the L type Ca 2+ channel were unchanged. Ventricular vulnerability was higher in EAM rats than in the control rats, and some of the ventricular arrhythmias observed in the EAM group seemed to be based on triggered activity. The level of expression of Kv4.2 mRNA was significantly reduced, and this change was compatible with prolongation of the action potential duration.
  • Role of KCNQ1 in the cell swelling-induced enhancement of the slowly activating delayed rectifier K+current
    Tomoyuki Kubota, Minoru Horie, Minoru Horie, Makoto Takano, Hidetada Yoshida, Hideo Otani, Shigetake Sasayama
    Japanese Journal of Physiology 52 31-39 2002年05月
    Cell swelling enhances a slowly activating delayed rectifier K + current (I Ks ) in cardiac cells. This investigation was undertaken to determine which of the two structural units reconstituting the I Ks channel, KCNQ1 (KvLQT1) and KCNE1 (minK/IsK), plays a key role in the cell swelling-induced I Ks enhancement and to dissect a possible involvement of tyrosine phosphorylation therein. KCNQ1 was transiently expressed alone or together with KCNE1 in a heterologous mammalian cell line. Two distinct whole-cell membrane currents were separately observed during the exposure of transfected cells to various degrees of hyposmotic solutions. A hyposmotic challenge (0.7 times control osmolarity) resulted in about a twofold increase not only in the heteromeric KCNQ1/KCNE1, but also in the homomeric KCNQ1 channel currents. There was no significant difference in the incremental ratio of current amplitude in response to hyposmotic stress between the two KCNQ1-related currents, and the cells expressing the heteromeric channels swelled less than those with the homomeric channels or without the exogenous ones. The cell swelling-induced I Ks enhancement was not affected by a protein tyrosine kinase (PTK) inhibitor, by genistein (50 μM), or by an inhibitor of phosphotyrosine phosphatase (PTP), orthovana-date (500 μM), or a nonhydrolyzable ATP analogue, AMP-PNP (5 mm). Taken together, it is very likely that KCNQ1 might primarily participate in the I Ks enhancement by osmotic cell swelling. The obligatory dependence of the I Ks augmentation on PTK activity remained to be demonstrated, at least, in this expression system.
  • History of cardiology in the last 100 years: Japanese contribution to studies on ATP sensitive potassium channel
    Akinori Noma, Minoru Horie, Makoto Takano
    Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 91 865-867 2002年01月
  • Long QT syndrome--therapy based on mechanism
    Minoru Horie
    Nippon rinsho. Japanese journal of clinical medicine 60 1389-1394 2002年01月
  • Evidence for a single nucleotide polymorphism in the KCNQ1 potassium channel that underlies susceptibility to life-threatening arrhythmias
    Tomoyuki Kubota, Minoru Horie, Minoru Horie, Makoto Takano, Makoto Takano, Hidetada Yoshida, Kotoe Takenaka, Eiichi Watanabe, Eiichi Watanabe, Takeshi Tsuchiya, Hideo Otani, Shigetake Sasayama
    Journal of Cardiovascular Electrophysiology 12 1223-1229 2001年12月
    Introduction: Congenital long QT syndrome (LQTS) is a genetically heterogeneous arrhythmogenic disorder caused by mutations in at least five different genes encoding cardiac ion c hannels. It was suggested recently that common polymorphisms of LQTS-associated genes might modify arrhythmia susceptibility in potential gene carriers. Methods and Results: We examined the known LQTS genes in 95 patients with definitive or suspected LQTS. Exon-specific polymerase chain reaction single-strand conformation polymorphism and direct sequence analyses identified six patients who carried only a single nucleotide polymorphism in KCNQ1 that is found in ∼ 11% of the Japanese population. This 1727G > A substitution that changes the sense of its coding sequence from glycine to serine at position 643 (G643S) was mostly associated with a milder phenotype, often precipitated by hypokalemia and bradyarrhythmias. When heterologously examined by voltage-clamp experiments, the in vitro cellular phenotype caused by the single nucleotide polymorphism revealed that G643S-KCNQ1 forms functional homomultimeric channels, producing a significantly smaller current than that of the wild-type (WT) channels. Coexpression of WT-KCNQ1 and G643S-KCNQ1 with KCNE1 resulted in ∼30% reduction in the slow delayed rectifier K + current I Ks without much alteration in the kinetic properties except its deactivation process, suggesting that the G643S substitution had a weaker dominant-negative effect on the heteromultimeric channel complexes. Conclusion: We demonstrate that a common polymorphism in the KCNQ1 potassium channel could be a molecular basis for mild I Ks dysfunction that, in the presence of appropriate precipitating factors, might predispose potential gene carriers to life-threatening arrhythmias in a specific population.
  • Disopyramide and its metabolite enhance insulin release from clonal pancreatic β-cells by blocking KATPchannels
    Minoru Horie, Nobuhisa Mizuno, Keiko Tsuji, Tetsuya Haruna, Tomonori Ninomiya, Hitoshi Ishida, Yutaka Seino, Shigetake Sasayama
    Cardiovascular Drugs and Therapy 15 31-39 2001年08月
    In an insulin-secreting pancreatic β-cell line (MIN6), insulin release was caused by disopyramide, an antiarrhythmic drug with Na-channel blocking action, and its main metabolite mono-isopropyl disopyramide (MIP). Insulin secretion, measured as immunoreactive insulin (IRI), was accelerated to 265.7% of the control by disopyramide and to 184.4% by MIP, with half-effective concentrations (EC 50 ) of 30.9±1.5 μM and 92.4±2.2 μM. We tested the possibility that these drugs induce insulin release by inhibiting ATP-sensitive K + (K ATP ) channels of MIN6 cells. In the cell-attached or ATP-free inside-out mode with patch membranes on MIN6 cells, K-selective channels were recorded with unitary conductance of 70.5 ± 3.5 pS (150 mM external K + ions at room temperature). The channels were concluded to be MIN6-K ATP channels because they were closed by extracellular high glucose (11.0 mM) or glibenclamide (200 nM) and were reversibly activated by diazoxide (50 μM). In the inside-out patch mode, they were inhibited by micromolar ATP. In both cell-attached and insideout mode, disopyramide and MIP inhibited single MIN6-K ATP channels. In the inside-out mode, they produced a dose-dependent inhibition of channel activity: the half-blocking concentrations (IC 50 ) were 4.8 ± 0.2 μM for disopyramide and 40.4 ± 3.1 μM for MIP. It was therefore concluded that both agents exert insulinotrphic effect through the inhibition of membrane K ATP channels in MIN6 cells.
  • Alteration of the membrane lipid environment by L-palmitoylcarnitine modulates KATPchannels in guinea-pig ventricular myocytes
    Tetsuya Haruna, Minoru Horie, Makoto Takano, Yutaka Kono, Hidetada Yoshida, Hideo Otani, Tomoyuki Kubota, Tomonori Ninomiya, Masaharu Akao, Shigetake Sasayama
    Pflugers Archiv European Journal of Physiology 441 200-207 2000年12月
    Sarcolemmal adenosine 5′-triphosphate-sensitive K + channels (K ATP ) are dramatically up-regulated by a membrane phospholipid, phosphatidyl-inositol-4,5-bisphosphate (PIP 2 ). During ischaemia, L-palmitoylcarnitine (L-PC), a fatty acid metabolite, accumulates in the sarcolemma and deranges the membrane lipid environment. We therefore investigated whether alteration of the membrane lipid environment by L-PC modulates the K ATP channel activity in inside-out patches from guinea-pig ventricular myocytes. L-PC (1 μM) inhibited K ATP channel activity, without affecting the single channel conductance, through interaction with Kir6.2. L-PC simultaneously enhanced the ATP sensitivity of the channel [concentration for half-maximal inhibition (IC 50 ) fell from 62.0±2.7 to 30.3±5.5 μM]. In contrast, PIP 2 attenuated the ATP sensitivity (IC 50 343.6±54.4 μM) and restored Ca 2+ -induced inactivation of K ATP channels (94.1±13.7% of the control current immediately before the Ca 2+ -induced inactivation). Pretreatment of the patch membrane with 1 μM L-PC, however, reduced the magnitude of the PIP 2 -induced recovery to 22.7.±6.3% of the control (P < 0.01 vs. 94.1±13.7% in the absence of L-PC). Conversely, after the PIP 2 -induced recovery, L-PC's inhibitory action was attenuated, but L-PC partly reversed the PIP 2 -mediated decrease in the ATP sensitivity (IC 50 fell from 310±19.2 to 93.1±9.8 μM). Thus, interaction between L-PC and PIP 2 in the plasma membrane appears to regulate K ATP channels.
  • The properties of the Kir6.1-6.2 tandem channel co-expressed with SUR2A
    Yutaka Kono, Minoru Horie, Makoto Takano, Hideo Otani, Lai Hua Xie, M. Akao, Keiko Tsuji, Shigetake Sasayama
    Pflugers Archiv European Journal of Physiology 440 692-698 2000年09月
    Functional ATP-sensitive K (K(ATP)) channels have an octameric subunit structure with four pore-forming subunits (Kir6.x) and four sulfonylurea receptors (SURx). In the present study, the properties of the heteromeric K(ATP) channel whose pore subunits are composed of Kir6.1 and Kir6.2 were examined using a heterologous expression system. In COS7 cells co-transfected with Kir6.1, Kir6.2 and SUR2A at a ratio of 1:1:2, K(ATP) channels showed various unitary conductances between those of Kir6.1/SUR2A (33.6±4.2 pS) and Kir6.2/SUR2A (67.1±1.6 pS). Kir6.1-6.2 tandem protein, constructed by fusing the C-terminus of Kir6.1 to the N-terminus of Kir6.2 with a ten glutamine linker sequence, also formed a channel with an intermediate conductance (58.9±1.5 pS). Kir6.2 and Kir6.1-6.2 showed similar sensitivity to ATP 4- : half-maximal inhibition (IC 50 ) was obtained at 14.1±12.8 μM and 17.6±9.6 μM, respectively. In the presence of Mg 2+ , Kir6.1-6.2 was significantly less sensitive than Kir6.2 to MgATP (IC 50 =95.5±49.6 μM versus 18.9±5.0 μM). These results suggest that Kir6.1 and Kir6.2 are endowed with the potential to form a heteromeric K(ATP) channel, which has a low sensitivity to MgATP.
  • ジギタリスによる虚血プレコンディショニング修飾の機序 -細胞膜ATP感受性カリウム・チャネルの機能的連関-
    堀江 稔, 春名 徹也, 河野 裕, 吉田 秀忠, 胡内 一郎, 縄田 隆三, 村上 知行, 篠山 重威
    心電図 20(2) 112-119 2000年03月
    ジギタリスは, 細胞膜Na/K-ATPase活性を阻害するが, 先に我々は, ジゴキシンが, 家兎梗塞モデルで観察される虚血プレコンディショニング (以下IPC) を阻害することを観察した.また, IPCを誘発するために行う5分間の冠動脈結紮は, その後のNa/K-ATPase活性のdown-regulationを有意に抑制することを報告した.一方, ATP感受性Kチヤネル (以下KATPチャネル) は, このIPCの発生機序におけるfinal common pathwayとして働くと考えられている.さらに, ジゴキシンのIPC阻害はKATPチャネル開口薬のcromakalimによりブロックされることが判明した.KATPチャネル活性を高めることによりIPC阻害が, 消失したことはNa/K-ATPaseとKATPチャネルの間になんらかの機能的な連関があることを示唆する, すなわち, Na/K-ATPase活性がIPC時に保たれることから, ポンプによる細胞膜直下fuzzy spaceのATPが消費され, そのレベルが低下することによりKATPチャネルが活性化する可能性が考えられた.
  • 欠損補綴における Removable Partial Denture の位置づけについて再考
    岩永 正憲, 堀江 稔
    日本顎咬合学会誌 : 咬み合わせの科学 = Journal of the Academy of Gnathology and Occlusion 23(3) 226-231 2003年09月
  • 心拍同期SPECT容積曲線分析による心機能評価と心筋脂肪酸代謝
    核医学 44(3) 285-286 2007年
  • Blockade of cardiac ATP-sensitive K+channel by cibenzoline targets its pore-forming subunit
    Minoru Horie, Minoru Horie, Masato Watanuki, Keiko Tsuji, Hitoshi Ishida, Ayako Ishida-Takahashi, Yousuke Yuzuki, Yutaka Seino, Shigetake Sasayama
    Journal of Cardiovascular Pharmacology 35 434-442 2000年03月
    Several antiarrhythmic agents with Na-channel blocking action have been shown to inhibit cardiac K(ATP) channels. We used cibenzoline to examine its precise target site using patch-clamp techniques and receptor binding assays in guinea-pig ventricular myocytes. Exposure of myocytes to a glucose-free perfusate containing 1 mM cyanide produced a time-dependent shortening of the action potential duration (APD) in the current-clamp mode. Cibenzoline (30 μM) slowed the development of APD shortening (APD 90 to ~91% vs. ~55% control 16 min after metabolic inhibition) at pH(o) 7.4, but not at pH(o) 6.4 (to ~60%). The pinacidil (30 μM)-induced K(ATP) currents were inhibited by cibenzoline in a PH(o)-dependent manner: the higher the pH(o), the stronger the blocking effect of cibenzoline. The binding of [ 3 H]-labeled cibenzoline was prevented by cibenzoline, but not by glibenclamide. Alkalinization produces a higher concentration of the uncharged form of cibenzoline, which can more easily permeate the cell membrane than the charged form. In NIH3T3 cells stably expressing Kir6.1, a putative pore-forming subunit of K(ATP) channel, cibenzoline but not glibenclamide inhibited the K conductance. Thus cibenzoline interacts with the channel pore-forming subunit of the K(ATP) channel (Kir6.2), but not the sulfonylurea receptor, from the cytosolic side after it permeates into the cell interior via the membrane lipid bilayer.
  • 心不全患者の予後評価における心筋脂肪酸代謝評価の臨床的有用性
    核医学 44(3) 283 2007年
  • Angiotensin II type 1 receptor blockade abolishes specific KATPchannel gene expression in rats with myocardial ischemia
    Masaharu Akao, Takahiro Sakurai, Minoru Horie, Hideo Otani, Makoto Takano, Ichiro Kouchi, Tomoyuki Murakami, Shigetake Sasayama
    Journal of Molecular and Cellular Cardiology 32 2239-2247 2000年01月
    The cardiac ATP-sensitive potassium (K ATP ) channel is potentially composed of an inward rectifier potassium channel (Kir6.1 and/or Kir6.2) subunit and the cardiac type of sulfonylurea receptor (SUR2A). We reported that cardiac Kir6.1 mRNA and protein are specifically upregulated in the non-ischemic as well as the ischemic regions in rats with myocardial ischemia, suggesting that humoral and/or hemodynamic factors are responsible for this regulation. In the present study, pretreatment with TCV-116, an angiotensin (Ang) II type 1 receptor antagonist, completely inhibited the upregulation of Kir6.1 mRNA and protein expression in both regions of rat hearts subjected to 60 min of coronary artery occlusion followed by 24 h of reperfusion; whereas pretreatment with lisinopril, an Ang converting enzyme (ACE) inhibitor, partly inhibited this upregulation. Except for rats pretreated with TCV-116, Kir6.1 mRNA levels were positively correlated with those for brain natriuretic peptide (BNP), a molecular indicator of regional wall stress, in both the non-ischemic and the ischemic regions. Plasma Ang II levels were not elevated in rats with control myocardial ischemia compared with sham rats. Thus, the stress-related induction of cardiac Kir6.1 mRNA and protein expression under myocardial ischemia is inhibited by pretreatment with an AT1 antagonist, but also in part by an ACE inhibitor, suggesting that activation of local renin-angiotensin system may play a role. © 2000 Academic Press.
  • 心室細動後の心肺蘇生に成功し、遺伝子診断により確定した先天性QT延長症候群(LQT1)の1例
    第20回 心臓性急死研究会 2007年
  • Agonist-independent modulation of L-type Ca currents by basal Gsprotein activities in single guinea pig ventricular myocytes
    Toshinori Makita, Minoru Horie, Lai Hua Xie, Yasunobu Okada, Shigetake Sasayama
    Heart and Vessels 15 233-239 2000年01月
    The modulation of L-type Ca 2+ currents (I Ca, L ) by the basal activities of G proteins was studied in adult guinea pig ventricular myocytes by whole-cell patch-clamp techniques. With intrapipette guanosine triphosphate (GTP) (100μM), a specific inhibition of G i proteins by pertussis toxin (PTX) produced an increase in the basal density of I Ca, L (from 11.0 ± 0.8, n = 13, to 25.0 ± 2.0pA/pF, n = 11, at 0mV test potential). In addition, PTX shifted the forskolin (Fsk) concentration-I Ca, L response relation significantly leftward (EC 50 = 63.7 ± 12.5 vs 625 ± 75nM). With intrapipette guanosine diphosphate (GDP)βS (1mM), the Fsk-I Ca, L relation was also shifted leftward (EC 50 = 197 ± 18.3 vs 781 ± 82.5 nM). However, chronic GDPβS dialysis accelerated the rundown of I Ca, L significantly, suggesting a potential contribution of G S proteins in maintaining basal I CaL . In contrast, intra-pipette GTPγS (100μM) produced a transient rise in I Ca, L from 11.0 ± 3.0 to 22.8 ± 7.0 pA/pF (in 3.4 min after whole-cell formation at 0mV, n = 9), presumably through the activation of G S proteins. It was followed by a gradual decline in I Ca, L (to 15.5 ± 3.5 pA/pF), which was still enhanced by Fsk (EC 50 = 1450 ± 98nM), indicating that the current decay was not solely due to rundown but to activation of G i proteins. G S , in addition to G i proteins, show sufficient basal activity to modulate I Ca, L in an agonist-independent manner.
  • Phospholipase C-linked receptors regulate the ATP-sensitive potassium channel by means of phosphatidylinositol 4,5-bisphosphate metabolism
    Lai Hua Xie, Minoru Horie, Makoto Takano
    Proceedings of the National Academy of Sciences of the United States of America 96 15292-15297 1999年12月
    In the COS7 cells transfected with cDNAs of the Kir6.2, SUR2A, and M 1 muscarinic receptors, we activated the ATP-sensitive potassium (K(ATP)) channel with a K + channel opener and recorded the whole-cell K(ATP) current. The K(ATP) current was reversibly inhibited by the stimulation of the M 1 receptor, which is linked to phospholipase C (PLC) by the G(q) protein. The receptor-mediated inhibition was observed even when protein kinase C (PKC) was inhibited by H-7 or by chelating intracellular Ca 2+ with 10 mM 1,2- bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate (BAPTA) included in the pipette solution. However, the receptor-mediated inhibition was blocked by U- 73122, a PLC inhibitor. M 1 -receptor stimulation failed to inhibit the K(ATP) current activated by the injection of exogenous phosphatidylinositol 4,5- bisphosphate (PIP 2 ) through the whole-cell patch pipette. The receptor- mediated inhibition became irreversible when the replenishment of PIP 2 was blocked by wortmannin (an inhibitor of phosphatidylinositol kinases), or by including adenosine 5'-[β,γ-imido]triphosphate (AMPPNP, a nonhydrolyzable ATP analogue) in the pipette solution. In inside-out patch experiments, the ATP sensitivity of the K(ATP) channel was significantly higher when the M 1 receptor in the patch membrane was stimulated by acetylcholine. The stimulatory effect of pinacidil was also attenuated under this condition. We postulate that stimulation of PLC-linked receptors inhibited the K(ATP) channel by increasing the ATP sensitivity, not through PKC activation, but most probably through changing PIP 2 levels.
  • Arrhythmias
    M. Horie, S. Sasayama
    Nippon rinsho. Japanese journal of clinical medicine 58 Suppl 1 754-757 2000年01月
  • Churg-Strauss syndrome presenting with massive pericardial effusion; case report and review of the literature.
    Heart Vessels  22(2) 128-130 2007年
  • Characterization of a novel missense mutation in the pore of HERG in a patient with long QT syndrome
    Hidetada Yoshida, Minoru Horie, Minoru Horie, Hideo Otani, Makoto Takano, Keiko Tsuji, Tomoyuki Kubota, Masatake Fukunami, Shigetake Sasayama
    Journal of Cardiovascular Electrophysiology 10 1262-1270 1999年10月
    Introduction: A new strategy to elucidate the molecular mechanisms underlying the long QT syndrome (LQTS) is now available with genetic mutational analyses and characterization of ion channel mutations. Methods and Results: In a 26-year-old woman with LQTS, we identified a novel missense mutation in the pore of HERG by using polymerase chain reaction/single-strand conformation polymorphism (PCR/SSCP) and sequencing of her genomic DNA. The mutation resulted in an amino acid substitution of a positively charged lysine for a highly conserved uncharged asparagine at codon 629 (N629K). Whole cell, patch clamp studies were conducted in COS7 cells by transfecting with wild-type (WT) and/or the mutant N629K HERG. The WT HERG produced an I(Kr)-like, E-4031-sensitive conductance with an inward rectification. In contrast, the cells transfected with the N629K HERG did not display any time- dependent current. Cotransfection of WT and N629K HERG (at a ratio of 1:1) produced a significantly smaller conductance when compared with WT HERG (WT 59.9 ± 7.3 pA/pF [n = 22] vs WT+N629K 5.5 ± 2.3 pA/pF In = 11] ; P < 0.01), but did not alter K + ion selectivity and tail current-voltage dependence. Because aprindine hydrochloride was effective in preventing ventricular tachycardias, we also tested the effect of the drug on WT HERG (I(Kr)) and KvLQT1/KCNE1 (I(Ks)) currents expressed in COS7. Conclusion: Functional analyses of a novel missense mutation in the pore of HERG suggest that the mutation causes marked reduction of I(Kr) via a dominant negative effect.
  • On the mechanism of genistein-induced activation of protein kinase A- dependent Cl-conductance in cardiac myocytes
    Kazuhiko Obayashi, Minoru Horie, Takashi Washizuka, Toshihisa Nishimoto, Shigetake Sasayama
    Pflugers Archiv European Journal of Physiology 438 269-277 1999年08月
    Genistein, an inhibitor of protein tyrosine kinase (PTK), enhanced the activation of the cardiac isoform of the protein kinase A (PKA)-regulated cystic fibrosis transmembrane conductance regulator (CFTR) Cl - conductance in guinea-pig ventricular cells. We examined the mechanism(s) underlying this excitatory action of genistein by using patch-clamp techniques. The CFTR Cl - conductance, activated by isoproterenol (ISO, 10 nM; [Cl - ] 153 mM extracellular, 21 mM intracellular; 36 °C), was enhanced by 20 μM genistein. Daidzein, a structural analogue of genistein with little inhibitory action on PTK, also enhanced CFTR Cl - currents. After maximal activation of the Cl - conductance by a cocktail of adenosine 3',5'-cyclic monophosphate, 3-isobutyl-1-methylxanthine and okadaic acid or vanadate plus forskolin in the pipette, genistein was no longer stimulatory but was rather slightly inhibitory at 100 μM. Direct exposure of myocytes to higher concentrations of genistein (50-100 μM) elicited outwardly rectifying currents with a reversal potential of -47 mV in the absence of ISO. In the presence of 50 μM H-89, a PKA inhibitor, genistein had no effect. Vanadate in the pipette at a concentration (100 μM) inhibiting phosphotyrosine phosphatases alone did not prevent the action of genistein. In contrast, no conductance was activated by tyrphostins B42 or 51 or lavendustin A, other PTK inhibitors. Genistein's stimulation of cardiac CFTR Cl - conductance appears to be independent of the PTK pathway and to be due to its direct interaction with CFTR Cl - channels.
  • 心筋虚血に伴うATP感受性カリウムチャネル遺伝子の調節
    堀江 稔, 赤尾 昌治, 河野 裕, 大谷 秀夫, 吉田 秀忠, 西本 紀久, 藍 智彦, 春名 徹也, 高橋 綾子, 胡内 一郎, 村上 知行, 鷹野 誠, 篠山 重威
    心電図 19(2) 131-135 1999年03月
  • Chymase inhibitor improves renal dysfunction under long-term angiotensin-converting enzyme inhibitor in heart failure
    第11回日本心不全学会 2007年
  • Comparison of BNP and NT-proBNP as a biomarker of heart failure
    第11回日本心不全学会 2007年
  • Cardiac sympathetic nerve activity is improved by chronic statin therapy in patients with nonischemic heart failure
    第11回日本心不全学会 2007年
  • Physiologically active BNP and C-reactive perotein contributes the regulation of plasma adiponectin in patients with decompasated heart failure
    第11回日本心不全学会 2007年
  • Left ventricular mass index as an important prognostic predictor in patients with heart failure
    第11回日本心不全学会 2007年
  • Angiotensin II Type 1 Receptor Partially Mediates Stretch-Induced Potentiation of the Slow Component of Delayed Rectifier Potassium Current in Guinea Pig Atrium
    The American Heart Association Scientific Sessions 2007 2007年
  • Age-Related Triggers for Life-Threatning Arrhythmia in the Genotyped Long QT Syndrome
    The American Heart Association Scientific Sessions 2007 2007年
  • Hyper Transcardiac Extraction of Aldosterone Promote Ventricular Remodeling and Cardiac Mass in Patients with Primary Aldosteronism
    The American Heart Association Scientific Sessions 2007 2007年
  • Familial Dilated Cardiomyopathy with Conduction Disease Caused by a Lamin A/C Mutation: Efficacy of the Cardiac Resynchronization Therapy with a Defibrillator
    The American Heart Association Scientific Sessions 2007 2007年
  • Chronic NADPH Oxidase Inhibition Improves Cardiac Dysfunction Through The Suppression Of Cardiac Oxidative Stress And The Renin-Angiotensin System In Heart Failure
    The American Heart Association Scientific Sessions 2007 2007年
  • 73)多臓器不全をきっかけに判明したミトコンドリア心筋症の一例(第101回日本循環器学会近畿地方会)
    國友 健生, 藤井 応理, 谷口 晋, 山本 孝, 高島 弘行, 松本 鉄也, 蔦本 尚慶, 堀江 稔, 江口 豊
    Circulation journal : official journal of the Japanese Circulation Society 70(0) 2006年10月
  • 遺伝子解析の新知見とその臨床応用 遺伝性不整脈のゲノム解析 (第5土曜特集 心不全UPDATE) -- (最近のトピックス)
    堀江 稔, 伊藤 英樹
    医学のあゆみ 218(14) 1361-1365 2006年09月
  • 診断の指針・治療の指針 心臓とアルドステロン
    蔦本 尚慶, 林 優, 堀江 稔
    綜合臨床 55(6) 1725-1727 2006年06月
  • 156)心外膜炎で発症したChurg-Strauss症候群の1症例(第100回日本循環器学会近畿地方会)
    内貴 乃生, 奥田 奈賀子, 松本 鉄也, 藤井 応理, 松尾 信郎, 伊藤 誠, 堀江 稔, 浜本 徹
    Circulation journal : official journal of the Japanese Circulation Society 70(0) 2006年04月
  • QT延長・短縮症候群 (シンポジウム 第57回福岡不整脈同好会)
    堀江 稔
    臨牀と研究 83(4) 603-605 2006年04月
  • 病態と診断の進歩 : 2. 不整脈と原因遺伝子
    伊藤 英樹, 堀江 稔
    日本内科学会雑誌 95(2) 203-208 2006年02月
    ここ10年の間で不整脈に関係する原因遺伝子が数多く報告されてきた. その多くは心筋細胞膜に発現するイオンチャネルか, これらのチャネルの膜発現に必要な構成蛋白である. 発現実験による機能解析から, 遺伝子異常が引き起こす機能変化と臨床像との関連が次第に明らかとなってきた. 今後, さらに新たな不整脈の原因遺伝子が発見されることが期待される.
  • 新薬の評価―カンデサルタン シレキセチル
    クリニカル プラクティス 25 143-144 2006年
  • ANPファミリーの新しい展開―ANPファミリー測定の臨床的意義
    Heart View  10 416-423 2006年
  • 慢性心不全の生化学診断
    CARDIAC PRACTICE  17(2) 143-150 2006年
  • 新薬インデックス
    2006クリニカルプラクティス増刊号 25 468-470 2006年
  • 心臓とアルドステロン
    総合臨床 55(6) 1725-1727 2006年
  • 検査値から診る―BNPの血中濃度測定
    循環plus メディカルトリビューン 6(10) 10-12 2006年
  • CRT-心不全治療に活かす―左室機能改善の機序
    Heart View メディカルビュー社 10(9) 50-55 2006年
  • 循環器薬の使い方―急性心不全
    medicina 43(9) 1460-1466 2006年
  • Brugada症候群
    Heart View 10(5) 568-573 2006年
  • QT延長・短縮症候群
    臨牀と研究 83(4) 603-605 2006年
  • Response to Letter Regarding Article, "Angiotensin II potentiates the slow component of delayed rectifier K+ current via the AT1 receptor in guinea pig atrial myocytes.
    Circulation 114 e566 2006年
  • アルドステロンと心不全 (特集 循環器疾患治療の新たなアプローチ:アルドステロンを見直す)
    蔦本 尚慶, 林 優, 堀江 稔
    呼吸と循環 53(12) 1241-1249 2005年12月
  • ダイジェスト版 : 心臓突然死の予知と予防法のガイドライン
    相澤 義房, 井上 博, 大江 透, 小川 聡, 奥村 謙, 笠貫 宏, 加藤 貴雄, 鎌倉 史朗, 古賀 義則, 原田 研介, 堀江 稔, 松崎 益徳, 三崎 拓郎, 三田村 秀雄, 山口 巖, 吉永 正夫, 池田 隆徳, 伊藤 誠, 江森 哲朗, 久賀 圭介, 児玉 逸雄, 佐々木 真吾, 清水 昭彦, 清水 渉, 住友 直方, 高月 誠司, 池主 雅臣, 新田 隆, 庭野 慎一, 野原 隆司, 藤木 明, 松田 直樹, 宮本 哲也, 村川 裕二, 鷲塚 隆
    Circulation journal : official journal of the Japanese Circulation Society 69 1253-1265 2005年11月
  • 心臓突然死の予知と予防法のガイドライン(循環器病の診断と治療に関するガイドライン(2003-2004年度合同研究班報告))
    相澤 義房, 井上 博, 大江 透, 小川 聡, 奥村 謙, 笠貫 宏, 加藤 貴雄, 鎌倉 史朗, 古賀 義則, 原田 研介, 堀江 稔, 松崎 益徳, 三崎 拓郎, 三田村 秀雄, 山口 巖, 吉永 正夫, 池田 隆徳, 伊藤 誠, 江森 哲朗, 久賀 圭介, 児玉 逸雄, 佐々木 真吾, 清水 昭彦, 清水 渉, 住友 直方, 高月 誠司, 池主 雅臣, 新田 隆, 庭野 慎一, 野原 隆司, 藤木 明, 松田 直樹, 宮本 哲也, 村川 裕二, 鷲塚 隆, 杉本 恒明, 中澤 誠, 堀 正二, 山口 徹
    Circulation journal : official journal of the Japanese Circulation Society 69(0) 1209-1265 2005年11月
  • 肺血症性肺塞栓にて発症した心室中隔欠損症に伴う感染性心内膜炎の一例(第99回日本循環器学会近畿地方会)
    吉野 知秀, 久松 隆史, 坪内 直也, 松本 鉄也, 堀江 稔, 浅井 徹, 白石 昭一郎
    Circulation journal : official journal of the Japanese Circulation Society 69(0) 2005年10月
  • マルチスライスCTによる心臓血管イメージング(第32回秋季学術大会)
    松尾 信郎, 堀江 稔
    日本放射線技術學會雜誌 61(9) 1309-1317 2005年09月
  • 不整脈と遺伝
    堀江 稔
    心電図 = Electrocardiology 25(4) 257-258 2005年07月
  • 診断の進歩 : 2. 体液因子による心不全の評価
    蔦本 尚慶, 堀江 稔
    日本内科学会雑誌 94(2) 221-227 2005年02月
    心不全では,心拍出量や血圧低下にともなう生体の代償機序によりさまざまな神経体液因子が血中,心臓組織中において上昇し病態の増悪進展と関係する.今後人口の高齢化にともない心不全患者が増加するのは間違いなく,ますます確実な診断と重症度評価が重要になると考えられる.心不全診断-重症度-予後-治療効果や病態を理解し,評価する上で, BNPなどの液性因子測定は心不全の生化学的指標として有用と考えられる.
  • 各種疾患におけるHOTの適応と臨床効果 慢性心不全における中枢性睡眠時無呼吸症候群(Cheyne-Stokes呼吸)と在宅酸素療法 (在宅呼吸管理の新展開) -- (在宅酸素療法(HOT))
    藤井 応理, 蔦本 尚慶, 堀江 稔
    日本胸部臨床 64(0) S72-77 2005年
  • 心不全診断に必要な検査:神経体液性因子測定の意義
    Heart View 9 34-40 2005年
  • 心不全治療におけるBNP測定の役割
    循環器科 57 230-238 2005年
  • 内科医に必要な栄養管理の知識
    心不全 診断と治療 93 1783-1787 2005年
  • アルドステロンと心不全
    呼吸と循環 53 1241-1249 2005年
  • 各種疾患におけるHOTの適応と臨床効果―慢性心不全における中枢性睡眠時無呼吸症候群(Cheyne-stokes呼吸).と在宅酸素療法
    日本胸部臨床 64(11) 72-77 2005年
  • 特定機能病院等における包括医療制度下で心臓核医学検査を日常診療でどのように使うか
    核医学 42(3) S226 2005年
  • Dilated cardiomyopathy relieved as a result of beta-blocker therapy: a case report-key point in assessment of prognosis based on MIBG myocardial scintigraphy ans BNP levels
    Ann Nucl Med 19 243-246 2005年
  • 79) 当院で短期間に経験した感染性心内膜炎の三症例(第96回日本循環器学会近畿地方会)
    西山 敬三, 環 愼二, 岡林 旅人, 川嶋 剛史, 堀江 稔, 白石 昭一郎, 浅井 徹
    Circulation journal : official journal of the Japanese Circulation Society 68(0) 2004年04月
  • Coordinate interaction between ATP-sensitive K+channel and Na+,K+- ATPase modulates ischemic preconditioning
    Tetsuya Haruna, Minoru Horie, Ichiro Kouchi, Ryuzo Nawada, Kunihiko Tsuchiya, Masaharu Akao, Hideo Otani, Tomoyuki Murakami, Tomoyuki Murakami, Shigetake Sasayama
    Circulation 98 2905-2910 1998年12月
    Background - We reported that digoxin abolishes the infarct size (IS)- limiting effect of ischemic preconditioning (IPC). Because ATP-sensitive K + (K(ATP)) channels are involved in IPC, we studied whether Na + , K + -ATPase had K(ATP) channels functionally interact, thereby modulating IPC. Methods and Results - Rabbits received 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. IPC was elicited by 5 minutes of occlusion followed by 10 minutes of reperfusion. The IS, expressed as a percentage of the area at risk, was 40.2±2.8% in control and 39.8±5.0% in digoxin pretreatment rabbits. Both IPC and pretreatment with cromakalim, a K(ATP) channel opener, reduced IS to 11.8±1.8% and 13.4±2.6% (P < 0.05 versus control). Digoxin abolished the reduction in IS induced by IPC (33.5±3.3%), whereas it did not change that induced by cromakalim (18.8±3.0%). In patch- clamp experiments, digoxin was found to inhibit the opening of K(ATP) channels in single ventricular myocytes in which ATP depletion had been induced by metabolic stress. In contrast, digoxin had little effect on the channel opening induced by cromakalim. Moreover, the inhibitory action of digoxin on channel activities was dependent on subsarcolemmal ATP concentration. Conclusions - The IS-limiting effect of IPC is modulated by an interaction between K(ATP) channels and Na + ,K + -ATPase through subsarcolemmal ATP.
  • 133) CARTOシステムが治療に有効であったincisional flutterの二例(第96回日本循環器学会近畿地方会)
    八尾 武憲, 久保田 知希, 小澤 友哉, 八木 崇文, 伊藤 誠, 堀江 稔, 杉本 喜久, 井上 輝郎
    Circulation journal : official journal of the Japanese Circulation Society 68(0) 2004年04月
  • Cytoplasmic terminus domains of Kir6.x confer different nucleotide-dependent gating on the ATP-sensitive K+ channel
    Makoto Takano, Lai Hua Xie, Hideo Otani, Minoru Horie
    Journal of Physiology 512 395-406 1998年10月
    1. In order to investigate the structural basis for the nucleotide-dependent gating of ATP sensitive K + channels (K(ATP)), Kir6.1 (uKATP-1), Kir6.2 (BIR1) and chimeric channels were co-expressed with a common subtype of sulphonylurea receptor, SUR1, in COS7 cells. Representing the amino terminal domain-transmembrane domain-carboxyl-terminal domain of Kir6.1 as 1-1-1. and of Kir6.2 as 2-2-2, chimeric Kir6.x channels were constructed by swapping the amino and/or carboxyl terminal domains between Kir6.1 and Kir6.2 to give the chimeric x-1-x channels 1-1-2, 2-1-1 and 2-1-2, and the chimeric x-2-x channels 2-2-1, 1-2-2 and 1-2-1. 2. Inside-out patch clamp experiments revealed that both wild-type Kir6.1 and Kir6.2 formed inwardly rectifying K + channels. Single-channel conductances were 36.3 and 66.1 pS, respectively. Chimeric x-1-x channels, whose transmembrane domain was that of Kir6.1, showed similar ion-pore properties to wild-type Kir6.1. Likewise, chimeric x-2-x channels had similar ion-pore properties to wild-type Kir6.2. 3. Wild-type Kir6.1 and Kir6.2 possessed distinct gating properties towards intracellular nucleotides. The activity of Kir6.1 was entirely dependent on Mg 2+ and nucleotide diphosphates (NDPs) such as UDP. In contrast, Kir6.2 was activated upon excision of patch membrane. When Kir6.2 underwent rundown, UDP reactivated the channel. 4. In order to eliminate UDP dependence from Kir6.1, it was necessary to replace both N- and C-termini; chimera 2-1-2 opened in UDP-free conditions. With Kir6.2, substitution of the N-terminus with that of Kir6.1 conferred UDP dependence on chimeras 1-2-2 and 1-2-1. Chimera 2-2-1 opened in UDP-free conditions, but UDP potentiated the channel activity by > 20-fold. 5. The kinetics of UDP-dependent activation were significantly different between Kir6.1 and Kir6.2. Kir6.1 maximally activated by UDP was sensitive to intracellular ATP, although its ATP sensitivity was significantly lower than that of Kir6.2 measured in identical conditions. The kinetics of UDP-dependent activation and ATP sensitivity could be transferred between Kir6.1. and Kir6.2 only when both N- and C-termini were replaced. We therefore concluded that nucleotide-dependent gating was regulated by the N- and C-terminal domains irrespective of the transmembrane domains.
  • Successful radiofrequency current catheter ablation of accessory atrioventricular pathway after tricuspid replacement in Ebstein's anomaly
    Tomohiko Ai, Minoru Horie, Minoru Horie, Takashi Washizuka, Carlos Albrecht, Toshihisa Nishimoto, Kazuhiko Obayashi, Kunihiko Tsuchiya, Masato Watanuki, Shigetake Sasayama
    Japanese Circulation Journal 62 791-793 1998年10月
    A 15-year-old female with Ebstein's anomaly was referred to hospital for radiofrequency (RF) current catheter ablation of her refractory paroxysmal supraventricular tachycardia (PSVT) after tricuspid valve replacement. A surface ECG showed ventricular preexcitation of type B Wolff-Parkinson-White (WPW) syndrome. In a baseline electrophysiological study, two types of PSVT with left and right bundle branch block (LBBB and RBBB) configurations were induced. The LBBB type was antidromic and the RBBB type was orthodromic atrioventricular reciprocating tachycardia (AVRT) with a right posterolateral accessory pathway. RF current was successfully delivered at the posterolateral site above the prosthetic valve (V-delta interval = -30 msec). The patient has been free from arrhythmias during a follow-up period of 9 months. RF current ablation seems to be useful for AVRT patients with corrected Ebstein's anomaly.
  • BNP測定における心不全患者の管理
    呼吸と循環 52 185-189 2004年
  • Accentuated antagonism by angiotensin II on guinea-pig cardiac L-type Ca-currents enhanced by β-adrenergic stimulation
    Tomohiko Ai, Minoru Horie, Kazuhiko Obayashi, Shigetake Sasayama
    Pflugers Archiv European Journal of Physiology 436 168-174 1998年06月
    To examine mechanism(s) underlying the accentuated antagonism by angiotensin II (A-II) on twitch tension, we recorded L-type Ca 2+ currents (I(Ca,L)) using conventional patch-clamp techniques in single, guinea-pig, ventricular myocytes. I(Ca,L) was recorded by a step-pulse protocol after eliminating K + conductances (internal Cs + plus tetraethylammonium chloride and K + -free extracellular solution). A-II (100 nM) did not affect basal I(Ca,L), but inhibited I(Ca,L) that had been enhanced (approximately 200% of control) by (ISO, isoproterenol 100 nM). The inhibitory action of A-II was concentration dependent (concentration eliciting 50% inhibition 88±9 pM, n=41) and the ISO-enhanced component of I(Ca,L) was completely blocked by A- II at concentrations above 10 nM. CV-11974 (500 nM), an A-II type-1 receptor (AT 1 ) antagonist, prevented the inhibitory action of A-II. Pre-incubation with pertussis toxin (PTX) abolished the inhibitory effect of A-II. A-II also inhibited the I(Ca,L) enhanced by histamine (500 nM) and forskolin (1 μM), but failed to affect I(Ca,L) enhanced by intracellular cyclic adenosine monophosphate (1 mM). The inhibitory action of A-II may therefore involve AT 1 receptors/PTX-sensitive, guanine nucleotide-binding (G) proteins (Gi)/adenylate cyclase and partially explains the A-II-dependent accentuated antagonism of inotropy.
  • BNPをどのように利用するか
    Medicina 41 1832-1835 2004年
  • Cystic fibrosis transmembrane conductance regulator mediates sulphonylurea block of the inwardly rectifying K+channel Kir6.1
    Ayako Ishida-Takahashi, Hideo Otani, Chiaki Takahashi, Takashi Washizuka, Keiko Tsuji, Makoto Noda, Minoru Horie, Minoru Horie, Shigetake Sasayama
    Journal of Physiology 508 23-30 1998年04月
    1. Recombinant ATP-sensitive K + channels (K(ATP) channels) were heterologously expressed in the NIH3T3 mouse cell line, and the electrophysiological properties were studied using patch-clamp techniques. 2. The NIH3T3 cell lines transfected with the inwardly rectifying K + channel Kir6.1 alone or with both Kir6.1 and cystic fibrosis transmembrane conductance regulator (CFTR) exhibited time-independent K + currents with weak inward rectification. In contrast, no measurable K + conductance was observed in mock-transfected cells or in cells transfected with CFTR alone. Regardless of co-transfection with Kir6.1, the transfection with CFTR produced a Cl - conductance that was activated by cell dialysis with cAMP (1 mM). The conductance was reversibly suppressed by glibenclamide (30 μM). 3. Whole-cell currents at +60 mV were blocked in a concentration-dependent manner by Ba 2+ ions with similar IC 50 values: 89.3 ± 23.3 μM (Kir6.1 alone) and 67.3 ± 24.9 μM (Kir6.1-CFTR). 4. The currents recorded from Kir6.1-transfected cells were not affected by glibenclamide, whereas glibenclamide did inhibit the conductance expressed in cells co-transfected with CFTR (IC 50 = 35.9 ± 6.6 μM). 5. In the cell-attached mode with a 150 mM K + pipette solution, both Kir6.1- and Kir6.1-CFTR-transfected cells displayed a class of K + channels showing weak inward rectification and a slope conductance of 50.7 ± 1.0 and 52.4 ± 4.9 pS, respectively. 6. In the inside-out mode, the single-channel currents recorded from both types of cells were not inhibited by intracellular ATP (1 mM). However, glibenclamide was found to block the single-channel activities in the co-transfected cells.
  • Erratum: (Journal of Clinical Investigation December 1997) 100:12 (3053- 3059))
    M. Akao, H. Otani, M. Horie, M. Takano, A. Kuniyasu, I. Kouchi, S. Sasayama, T. Murakami
    Journal of Clinical Investigation 101 915 1998年02月
  • Functional communication between cardiac ATP-sensitive K+channel and Na/K ATPase
    Kunihiko Tsuchiya, Minoru Horie, Minoru Horie, Tetsuya Haruna, Tomohiko Ai, Toshihisa Nishimoto, Hisayoshi Fujiwara, Shigetake Sasayama
    Journal of Cardiovascular Electrophysiology 9 415-422 1998年01月
    Introduction: Functional interaction between K(ATP) channel and Na/K ATPase was studied in single guinea pig ventricular myocytes because both membrane molecules are known to be involved in ischemic episodes. Methods and Results: K(ATP) channel currents were recorded at 36°C by using whole cell, cell-attached, inside-out, and open cell-attached modes of patch clamp techniques on enzymatically isolated ventricular myocytes. In the whole cell mode, ouabain (1μM) reversibly inhibited the K(ATP) currents induced by metabolic stress (ATP-free pipette solution and 1 mM NaCN), but not those activated by cromakalim (100 μM), a K(ATP) channel opener. In the cell- attached mode, ouabain concentration dependently inhibited K(ATP) channel opening induced by metabolic suppression (5.5 mM 2-deoxyglucose and 1 mM CN - ). Half-inhibition concentration for ouabain was 21.0 ± 5.5 nM and the Hill coefficient was 0.8 ± 0.1 (n = 26). However, ouabain did not have an effect on the channel activity induced by cromakalim (100 μM). In the inside-out mode, ouabain applied to the internal side of membrane did not affect the channel. In the open cell-attached mode made by preincubation with streptolysin-O (0.08 U/mL), the K(ATP) channels were not activated by the metabolic inhibitors but were by reducing extracellular ATP concentrations, because subsarcolemmal ATP concentration could be controlled through tiny membrane holes. The channels thus activated were not suppressed by ouabain. Conclusion: The inhibition of Na/K ATPase by ouabain appeared to block the K(ATP) channels by accumulating subsarcolemmal ATP caused by a decrease of the transition from ATP to ADP. In the presence of ischemic episodes, the administration of digitalis compounds may affect the opening of K(ATP) channels, which is primarily protective against the development of irreversible myocardial damage.
  • Metabolic inhibition impairs ATP-sensitive K+ channel block by sulfonylurea in pancreatic β-cells
    Eri Mukai, Eri Mukai, Hitoshi Ishida, Seika Kato, Yoshiyuki Tsuura, Shimpei Fujimoto, Ayako Ishida-Takahashi, Minoru Horie, Kinsuke Tsuda, Yutaka Seino
    American Journal of Physiology - Endocrinology and Metabolism 274 1998年01月
    The effect of metabolic inhibition on the blocking of β-cell ATP- sensitive K + channels (K(ATP) channels) by glibenclamide was investigated using a patch-clamp technique. Inhibition of K(ATP) channels by glibenclamide was attenuated in the cell-attached mode under metabolic inhibition induced by 2,4-dinitrophenol. Under a low concentration (0.1 μM) of ATP applied in the inside-out mode, K(ATP) channel activity was not fully abolished, even when a high dose of glibenclamide was applied, in contrast to the dose- dependent and complete K(ATP) channel inhibition under 10 μM ATP. On the other hand, cibenzoline, a class Ia antiarrhythmic agent, inhibits KATe channel activity in a dose-dependent manner and completely blocks it, even under metabolic inhibition. In sulfonylurea receptor (SUR1)- and inward rectifier K + channel (Kir6.2)-expressed proteins, cibenzoline binds directly to Kir6.2, unlike glibenclamide. Thus, K(ATP) channel inhibition by glibenclamide is impaired under the condition of decreased intracellular ATP in pancreatic β-cells, probably because of a defect in signal transmission between SUR1 and Kir6.2 downstream of the site of sulfonylurea binding to SUR1.
  • CFTR as a Mutifunctional Channel Regulator
    Minora Horie, Minora Horie
    Nippon Nogeikagaku Kaishi 71 812-814 1997年12月
  • Functional compartmentalization of ATP is involved in angiotensin II- mediated closure of cardiac ATP-sensitive K+channels
    Kunihiko Tsuchiya, Minoru Horie, Minoru Horie, Masato Watanuki, Carlos A. Albrecht, Kazuhiko Obayashi, Hisayoshi Fujiwara, Shigetake Sasayama
    Circulation 96 3129-3135 1997年11月
    Background: The effects of angiotensin II (Ang II) on ATP-sensitive K + channels (K(ATP)) were investigated in ventricular myocytes enzymatically isolated from adult guinea pig heart. Methods and Results: In the whole-cell and cell-attached configurations (including open-cell-attached mode) of the patch-clamp technique, K(ATP) currents (I(KATP)) were activated through metabolic poisoning by the use of inhibitors of both glycolytic and oxidative ATP productions at 37°C. In the whole-cell mode, I(KATP) were reversibly suppressed by increasing extracellular glucose and Ang II (1 nmol/L). In the cell-attached mode, Ang II concentration-dependently inhibited single K(ATP) activities with an IC 50 value of 3.2±0.5 pmol/L (Hill coefficient = 1.3±0.3). CV11974 (100 nmol/L), an angiotensin 1 (AT 1 ) receptor-selective antagonist, blocked the inhibitory action of Ang II. Preincubation of myocytes with pertussis toxin (5 μg/mL for > 120 min at 37°C) virtually prevented subsequent Ang II action. The inhibitory effect of Ang II was also abolished in the open-cell-attached mode (achieved by a prior perfusion of streptolysin-O, 0.08 U/mL). In this mode, through tiny membrane holes, the intracellular ATP concentration can be controlled by bathing extracellular solutions containing a known ATP concentration. Conclusions: The inhibitory actions of Ang II on K(ATP) appear to be mediated by an increase in the subsarcole mmal ATP concentration that results from the inhibition of adenylate cyclase activities via AT 1 receptors/PTX-sensitive G proteins.
  • Endothelin-1 inhibits the slow component of cardiac delayed rectifier K+currents via a pertussis toxin-sensitive mechanism
    Takashi Washizuka, Minoru Horie, Minoru Horie, Masato Watanuki, Shigetake Sasayama
    Circulation Research 81 211-218 1997年08月
    Endothelin-1 (ET-1) is a 21-amino acid peptide hormone released from myocardial and endothelial cells, whose receptors (both ET(A) and ET(B)) are expressed in the myocardium. We report here that ET-1 inhibits the cardiac delayed rectifier K + current (I(K)) via a pertussis toxin (PTX)sensitive mechanism. Ventricular myocytes enzymatically isolated from guinea pig hearts were voltage-clamped by the conventional whole-cell and nystatin-perforated patch technique (intrapipette and extrapipette K + concentrations, 150 and 5.4 mmol/L, respectively) in the presence of nifedipine (2 μmol/L). Amplitudes of tail and steady state (2-second pulse) currents were measured as I(K). ET-1 suppressed the basal I(K) by 20.9±2.3% in a concentration- dependent manner, with an IC 50 of 1.1±0.3 nmol/L (n=19), although it did not suppress the basal I(K) using the nystatin method. E-4031 (5 μmol/L), a blocker of the rapid component of I(K) (I(Kr)), did not prevent the inhibitory action of ET-1. ET-1 reduced by 63.4±6.5% the slow component of I(K) (I(Ks)) that had been enhanced to ≃2-fold by isoproterenol (ISO, 20 nmol/L). The action was concentration dependent, with an IC 50 of 0.7±0.4 nmol/L (n=22), and was also observed using the nystatin method. The effect of ET-1 appeared to be mediated by an ETA receptor, because it was prevented by FR139317, an ET(A)-selective antagonist (1 μmol/L, n=4), and sarafotoxin S6c, an ET(B)-selective agonist (100 nmol/L, n=4), could not inhibit the ISO- enhanced I(K). ET-1 antagonized I(Ks) enhanced by histamine (250 nmol/L, n=7) and forskolin (500 nmol/L, n=7) but did not inhibit I(Ks) enhanced by the internal application of cAMP (100 μmol/L, n=6). Preincubation of myocytes with PTX (5 μg/mL for > 60 minutes at 36°C) completely abolished the inhibitory action of ET-1 on the ISO-enhanced I(Ks) (n=4). Thus, nanomolar ET-1 inhibits I(Ks) via the ET(A) receptor/PTX-sensitive G protein/PKA pathway.
  • Endothelin-1 inhibition of cardiac ATP-sensitive K+channels via pertussis-toxin-sensitive G-proteins
    Masato Watanuki, Minoru Horie, Minoru Horie, Kunihiko Tsuchiya, Kazuhiko Obayashi, Shigetake Sasayama
    Cardiovascular Research 33 123-130 1997年01月
    Objective: Secretion of endothelin-1 (ET-1) and activation of cardiac ATP-sensitive K + (K(ATP)) channels are facilitated under myocardial metabolic stress. The aim of this study was to investigate the effects of ET-1 on K(ATP) channels and to assess underlying mechanisms in ventricular myocytes. Methods: Single channel currents were measured with the voltage-clamp technique in cell-attached patches from enzymatically-isolated single guinea pig ventricular myocytes. In some experiments, the open-cell-attached mode was employed by permeating the membrane with streptolysin-O. Results: ET-1 concentration-dependently inhibited single K(ATP) channel currents, which had been activated by metabolic poisoning, with an IC 50 of 3.8 ± 0.7 pM. BQ-123, an ET(A) receptor-selective antagonist, reduced the effects of ET-1. ET-1 effects were largely abolished in the myocytes pre-incubated with pertussis toxin. In the open-cell-attached mode, where the intracellular ATP concentration ([ATP]) could be virtually controlled, the effects of ET-1 were abolished. Muscarinic receptor stimulation inhibited the channels in a similar manner to ET-1, whereas β-adrenoceptor stimulation accelerated channel activation. By analogy, ouabain also inhibited K(ATP) channel activity under metabolic stress presumably because inhibition of the Na + /K + pump spares subsarcolemmal ATP. ET-1 inhibited the K(ATP) channels that had been reactivated in the continuous presence of ouabain. Conclusions: ET-1 reversibly inhibited K(ATP) channels. This effect appears to be mediated by an increase in subsarcolemmal [ATP] which results from inhibition of adenylate cyclase activities through PTX-sensitive G-proteins coupled to ET(A) receptors.
  • Vaughan Williams class IV antiarrhythmic drugs
    M. Horie, T. Washizuka, S. Ikeguchi, S. Sasayama
    Nippon rinsho. Japanese journal of clinical medicine 54 2132-2137 1996年08月
    Vaughan Williams class IV antiarrhythmic drugs have Ca-channel blocking actions. Since L-type Ca-channels play key roles in regulating pulse conduction in atrioventricular node as well as in pathologically-depolarized myocardium, Ca-channel blockers known to modulate this type of Ca-channel (ICa,L) are used as antiarrhythmic agents. ICa,L channels have relatively high threshold potential (-40 mV) to activate and long-opening properties, and are enhanced by beta-adrenergic stimulation. Among three major ICa,L blockers, dihydropyridines such as nifedipine were found to bind to the channel from extracellular side. In contrast, verapamil and diltiazem interact with the channel from the cytoplasmic side, thereby causing rate-dependent block of ICa,L channels. This sideness of pharmacological action of the Ca-channel blockers determines an important therapeutic modality and their indication for tachyarrhythmias.
  • Alterations in basal and glucose-stimulated voltage-dependent Ca2+ channel activities in pancreatic β cells of non-insulin-dependent diabetes mellitus GK rats
    Seika Kato, Seika Kato, Hitoshi Ishida, Yoshiyuki Tsuura, Kazuo Tsuji, Masayoshi Nishimura, Minoru Horie, Tomohiko Taminato, Susumu Ikehara, Hiroyuki Odaka, Hitoshi Ikeda, Yasunobu Okada, Yutaka Seino
    Journal of Clinical Investigation 97 2417-2425 1996年06月
    In genetically occurring non-insulin-dependent diabetes mellitus (NIDDM) model rats (GK rats), the activities of L- and T-type Ca 2+ channels in pancreatic β cells are found to be augmented, by measuring the Ba 2+ currents via these channels using whole-cell patch-clamp technique, while the patterns of the current-voltage curves are indistinguishable. The hyper-responsiveness of insulin secretion to nonglucose depolarizing stimuli observed in NIDDM β cells could be the result, therefore, of increased voltage-dependent Ca 2+ channel activity. Perforated patch-clamp recordings reveal that the augmentation of L-type Ca 2+ channel activity by glucose is markedly less pronounced in GK β cells than in control β cells, while glucose-induced augmentation of T-type Ca 2+ channel activity is observed neither in the control nor in the GK β cells. This lack of glucose-induced augmentation of L-type Ca 2+ channel activity in GK β cells might be causatively related to the selective impairment of glucose-induced insulin secretion in NIDDM β cells, in conjunction with an insufficient plasma membrane depolarization due to impaired closure of the ATP-sensitive K + channels caused by the disturbed intracellular glucose metabolism in NIDDM β cells.
  • Block of pancreatic ATP-sensitive K+channels and insulinotrophic action by the antiarrhythmic agent, cibenzoline
    Ayako Ishida-Takahashi, Minoru Horie, Minoru Horie, Yoshiyuki Tsuura, Hitoshi Ishida, Tomohiko Ai, Shigetake Sasayama
    British Journal of Pharmacology 117 1749-1755 1996年01月
    1 We investigated the effect of cibenzoline (a class Ia antiarrhythmic drug) on basal insulin secretory activity of rat pancreatic islets and ATP-sensitive K ATP channels (K ATP ) in single pancreatic βcells of the same species, using radioimmunoassay and patch clamp techniques. 2 Micromolar cibenzoline had a dose-dependent insulinotrophic action with an EC 50 of 94.2 ± 46.4 μM. The compound inhibited the activity of the K ATP channel recorded from a single β-cell in a concentration-dependent manner. The IC 50 was 0.4 μM in the inside-out mode and 5.2 μM in the cell-attached mode, at pH 7.4. 3 In the cell-attached mode, alkalinization of extracellular solution increased the inhibitory action of cibenzoline and the IC 50 was reduced from 26.8 μM at pH 6.2 to 0.9 μM at pH 8.4. On the other hand, the action of cibenzoline in the excised inside-out mode was acute in onset with a small IC 50 , indicating that the drug attains its binding site from the cytoplasmic side of the cell membrane. 4 In the inside-out mode, micromolar ADP reactivated the cibenzoline-blocked K ATP channels in a manner similar to that by which ADP restored ATP-dependent block of the channel. 5 The binding of [ 3 H]-glibenclamide to pancreatic islets was inhibited by glibenclamide but not by cibenzoline. In contrast, the [ 3 H]-cibenzoline binding was displaced by unlabelled cibenzoline but not by glibenclamide. It is concluded that cibenzoline blocks pancreatic K ATP channels via a binding site distinct from the sulphonylurea receptor.
  • Glibenclamide, an ATP-sensitive K+channel blocker, inhibits cardiac cAMP-activated Cl-conductance
    Makoto Tominaga, Makoto Tominaga, Minoru Horie, Shigetake Sasayama, Yasunobu Okada
    Circulation Research 77 417-423 1995年01月
    Stimulation of the β-adrenoceptor activates a time-independent Cl - conductance that is known to be regulated via phosphorylation by cAMP- dependent protein kinase in guinea pig ventricular myocytes. Since epithelial cystic fibrosis transmembrane conductance regulator Cl - channels are known to be sensitive to an antidiabetic sulfonylurea, glibenclamide, we tested whether the drug modulates cardiac cAMP-activated Cl - conductance. Bath application of isoproterenol (1 μmol/L, n = 11) or forskolin (1 μmol/L, n= 17) or the intracellular application of cAMP (1 mmol/L, n = 9) activated whole-cell Cl - currents recorded from single myocytes at 36°C. External glibenclamide (≥10 μmol/L, n = 26) inhibited the Cl - current induced by either of the stimulants in a concentration-dependent manner. The half- maximal inhibition concentration (IC 50 ) of glibenclamide and the Hill coefficient were 24.5 to 37.9 μmol/L and 1.6 to 2.2, respectively. During current-clamp experiments, forskolin was found to shorten the action potential significantly (250 ± 45 to 201 ± 52 milliseconds, P < .05) in 7 of 11 cells tested. Glibenclamide antagonized the forskolin-induced shortening (to 243 ± 54 milliseconds, n = 7, P < .05). Intracellular administration of sodium orthovanadate (0.5 to ≃1 mmol/L, n = 6) brought about persistent activation of Cl - current after brief bath application of forskolin. This Cl - current was not affected by H-89 (100 μmol/L, n = 3), a specific inhibitor of cAMP-dependent protein kinase, and was suppressed by glibenclamide similarly, with an IC 50 of 29.7 μmol/L. Thus, it is concluded that glibenclamide inhibits cardiac cAMP-activated Cl - channels at some step(s) downstream from the phosphorylation/dephosphorylation process.
  • Reduced sensitivity of dihydroxyacetone on ATP-sensitive K+ channels of pancreatic beta cells in GK rats
    Y. Tsuura, H. Ishida, Y. Okamoto, S. Kato, M. Horie, H. Ikeda, Y. Seino
    Diabetologia 37 1082-1087 1994年11月
    In the GK (Goto-Kakizaki) rat, a genetic model of non-insulin-dependent diabetes mellitus, glucose-induced insulin secretion is selectively impaired. In addition, it has been suggested by previous studies that impaired glucose metabolism in beta cells of the GK rat results in insufficient closure of ATP-sensitive K + channels (K ATP channels) and a consequent decrease in depolarization, leading to a decreased insulin release. We have recently reported that the site of disturbed glucose metabolism is probably located in the early stages of glycolysis or in the glycerol phosphate shuttle. In the present study, in order to identify the impaired metabolic step in diabetic beta cells, we have investigated insulin secretory capacity by stimulation with dihydroxyacetone (DHA), which is known to be directly converted to DHA-phosphate and to preferentially enter the glycerol phosphate shuttle. In addition, using the patch-clamp technique, we also have studied the sensitivity of DHA on the K ATP channels of beta cells in GK rats. The insulin secretion in response to 5 mmol/l DHA with 2.8 mmol/l glucose was impaired, and DHA sensitivity of the K ATP channels was reduced in beta cells of GK rats. From these results, we suggest that the intracellular site responsible for impaired glucose metabolism in pancreatic beta cells of GK rats is located in the glycerol phosphate shuttle. © 1994 Springer-Verlag.
  • 心電学の基礎と応用  イオンチャネル  受容体によるイオンチャネルの制御:受容体によるイオンチャネルの制御
    堀江 稔
    心電図 17(6) 740-746 1997年
  • Increased calcium-channel currents of pancreatic β cells in neonatally streptozocin-induced diabetic rats
    Seika Kato, Seika Kato, Seika Kato, Hitoshi Ishida, Hitoshi Ishida, Hitoshi Ishida, Yoshiyuki Tsuura, Yoshiyuki Tsuura, Yoshiyuki Tsuura, Yoshimasa Okamoto, Yoshimasa Okamoto, Yoshimasa Okamoto, Kazuo Tsuji, Kazuo Tsuji, Kazuo Tsuji, Minoru Horie, Minoru Horie, Minoru Horie, Yasunobu Okada, Yasunobu Okada, Yasunobu Okada, Yutaka Seino, Yutaka Seino, Yutaka Seino
    Metabolism 43 1395-1400 1994年01月
    Using a whole-cell patch-clamp technique, voltage-dependent Ca 2+ -channel activities were found to be increased in cultured single β cells isolated from neonatally streptozocin-induced diabetic rats (NSZ rats). The current-voltage relationship and inactivation time course of Ba 2+ currents via L-type Ca 2+ channels were indistinguishable between NSZ and control rats. However, the current density observed in NSZ rats was significantly greater than that in control rats. Ba 2+ currents via T-type Ca 2+ channels were also found to be enhanced in NSZ β cells. The insulin-secretory capacity of cultured pancreatic islets in response to a depolarizing stimulus (20 mmol/L arginine or 30 mmol/L KCl) in the presence of 11.1 mmol/L glucose was augmented in NSZ rats, whereas that in response to 11.1 and 16.7 mmol/L glucose alone was significantly reduced. It is concluded that the impaired insulinotropic action of glucose in β cells in NSZ rats is not due to reduced activity of voltage-dependent Ca 2+ channels. The fact that insulin secretion induced by a depolarizing stimulus was enhanced in NSZ rats may be related to the augmented activity of the voltage-dependent calcium current found in NSZ β cells. © 1994.
  • Glucose sensitivity of ATP-sensitive K+ channels is impaired in β-cells of the GK rat: A new genetic model of NIDDM
    Yoshiyuki Tsuura, Hitoshi Ishida, Yoshimasa Okamoto, Seika Kato, Kimihiko Sakamoto, Minoru Horie, Hitoshi Ikeda, Yasunobu Okada, Yutaka Seino
    Diabetes 42 1446-1453 1993年10月
    In the Goto-Kakizaki rat, a new genetic model of NIDDM, insulin response to glucose is selectively impaired. To elucidate the mechanism of this abnormality, we studied the properties of ATP-sensitive K + channels, the inhibition of which is a key step of insulin secretion induced by fuel substrates, using the patch-clamp technique. The glucose-sensitivity of K ATP channels was considerably reduced in GK rats. However, the inhibitory effects of ATP on channel activity and unitary conductance were not significantly different between control and GK rats. Thus, it appears that the impaired insulinotropic action of glucose in β-cells of GK rats is attributable to insufficient closure of the K ATP channels, probably because of deficient ATP production by impaired glucose metabolism. KATP-channel activities in both control and diabetic β-cells were found to be equally suppressed by glyceraldehyde and 2-ketoisocaproate. These results strongly suggest that the step responsible for the metabolic dysfunction of diabetic β-cells is located within the glycolytic pathway before glyceraldehyde-3-phosphate or in the glycerol phosphate shuttle.
  • Disopyramide blocks pancreatic ATP-sensitive K+channels and enhances insulin release
    S. Hayashi, M. Horie, Y. Tsuura, H. Ishida, Y. Okada, Y. Seino, S. Sasayama
    American Journal of Physiology - Cell Physiology 265 1993年09月
    An antiarrhythmic agent, disopyramide, was found to enhance the insulin secretory capacity of Wistar rat pancreatic islets with a half-maximal concentration of 23.3 μM. Employing a patch-clamp technique, disopyramide was found to inhibit ATP-sensitive K + (K(ATP)) channel activity in rat pancreatic β-cells in primary culture without altering the unitary conductance. Half-maximal inhibition was achieved by the addition of 3.6 μM disopyramide to the intracellular bathing solution in the inside-out mode, 11.0 μM to the extracellular bathing solution in the outside-out mode, and 87.4 μM in the cell-attached mode. The binding of [ 3 H]glibenclamide to pancreatic islets was inhibited by unlabeled glibenclamide but not by unlabeled disopyramide. Based on these observations, it is concluded that disopyramide blocks pancreatic K(ATP) channels via binding to a site(s) distinct from the sulfonylurea receptor. This effect may be causatively involved in disopyramide-induced hypoglycemia.
  • Ionic mechanism of minoxidil sulfate-induced shortening of action potential durations in guinea pig ventricular myocytes
    S. Hayashi, M. Horie, Y. Okada
    Journal of Pharmacology and Experimental Therapeutics 265 1527-1533 1993年01月
    Patch-clamp techniques were used to study pharmacological effects of minoxidil sulfate (MNXS) on the membrane currents of enzymatically isolated guinea pig ventricular myocytes. In the whole-cell current-clamp mode, MNXS (100 μM) shortened the action potential duration without affecting the resting membrane potential. This action was antagonized in part by 1 μM glibenclamide, a specific blocker of ATP-sensitive K + channel. Under the whole-cell voltage-clamp condition, MNXS increased the time-independent outward current, in a dose-dependent manner, at voltages more positive to - 73.5 mV. This MNXS-induced outward current was inhibited completely by 1 μM glibenclamide. In inside-out patch membranes, MNXS (100 μM) applied to the cytosolic side produced a reversible activation of ATP-sensitive K + channels. This MNXS-dependent increase in the single-channel activity was abolished by increasing the ATP concentration to 3 mM or by adding 1 μM glibenclamide. Even after complete rundown of the channel activity in inside- out patches, MNXS could reactivate in part the channel in 22 of 35 patches. In addition, MNXS was found to suppress whole-cell L-type Ca ++ channel currents in a dose-dependent manner. This MNXS effect on Ca ++ currents was not antagonized by 1-3 μM glibenclamide. We conclude that MNXS shortens the cardiac action potential duration by both increasing ATP-sensitive K + channel currents and decreasing L-type Ca ++ channel currents.
  • Comparative studies of ATP sensitive potassium channels in heart and pancreatic β cells using Vaughan-Williams class ia antiarrhythmics
    Minora Horie, Seiji Hayashi, Yousuke Yuzuki, Shigetake Sasayama
    Cardiovascular Research 26 1087-1094 1992年11月
    Objective: Actions of cibenzoline and disopyramide, agents with Vaughan-Williams class la antiarrhythmic action, on ATP sensitive K + (K ATP ) channels were examined in heart and pancreatic β cells. Methods: Single ventricular myocytes and β cells were prepared enzymatically from adult Wistar rat hearts and pancreatic islets. Using patch clamp techniques, K ATP channel activities were recorded in whole cell and single channel modes. In whole cell experiments, myocytes were bathed with Tyrode's medium (34°C); inside out patches were bathed with internal solutions (22-24°C) containing 1 (μM ATP and varying concentrations of cibenzoline or disopyramide. Myocytes were voltage clamped at -40 mV and glibenclamide blockable conductance was produced by cromakalim. Results: Micromolar concentrations of both cibenzoline and disopyramide suppressed cromakalim induced conductance. When applied to the cytosolic surface of the cell membrane in inside out configuration, both drugs reversibly inhibited single K ATP channel activities. Neither unitary conductance nor intraburst fast kinetics was affected by the compounds. At a holding potential of -40 mV under symmetrical ∼ 150 mM K + conditions, half maximum doses (IC 50 ) were 0.9 μM [Hill coefficient (h)=1.3] for cibenzoline induced block of cardiac K ATP channels and 1.8 μM (h=1.0) for disopyramide block. At +40 mV, IC 50 for cibenzoline block was 1.4 μM (h=0.9). Thus there was little voltage dependence in cibenzoline induced channel block. A similar IC 50 value of 2.5 μM (h=1.2 at -60 mV under symmetrical ∼ 150 mM K + ) was observed for cibenzoline induced block of K ATP channels. Conclusions: Near therapeutic concentrations of cibenzoline and disopyramide inhibit K ATP channel activities in both heart and pancreatic β cells. This may be causally related to the fasting hypoglycaemia which is sometimes reported in patients receiving the drugs. These antiarrhythmic agents may also modulate myocardial electrical properties during hypoxia or ischaemia.Cardiovascular Research 1992;26:1087-1094.
  • Impaired glucose sensitivity of ATP-sensitive K+channels in pancreatic β-cells in streptozotocin-induced NIDDM rats
    Y. Tsuura, H. Ishida, Y. Okamoto, K. Tsuji, T. Kurose, M. Horie, H. Imura, Y. Okada, Y. Seino
    Diabetes 41 861-865 1992年07月
    ATP-sensitive K + channels (K(ATP) channels) are known to play a key role in the cellular mechanism of insulin secretion from pancreatic β cells. In order to examine the possible impairment of K(ATP) channel function in non- insulin-dependent diabetes mellitus (NIDDM), we have studied the properties of the K(ATP) channels in single β cells of neonatally streptozotocin- induced diabetic rats (NSZ rats) using the patch-clamp technique. The unitary conductance of the channel in diabetic β-cells was virtually identical to that in control β cells and there was no difference in the sensitivity to ATP and glibenclamide of K(ATP) channels between the NIDDM and control groups. In response to glucose, the activity of the K(ATP) channels was diminished in a dose-dependent manner in both control and diabetic cells. However, the inhibition of the K(ATP) channels in β-cells of NSZ rats was significantly less than that in control cells. Even in the presence of 11.1 mM glucose, the openings of a few single K(ATP) channels were consistently observed in cell-attached patch membranes of diabetic, but not control, β- cells. Thus, it appears that the impaired insulinotropic action of glucose in β-cells in NSZ rats is associated with a reduced sensitivity of the K(ATP) channel to glucose, but not to ATP, presumably due to a deficiency in glucose metabolism.
  • Intra-pipette GTP prevents the rapid rundown of β-adrenoceptor-mediated activation of Cl current in isolated guinea-pig ventricular myocytes
    M. Horie, H. Tzyh-Chang, D. C. Gadsby
    Journal of Physiology 446 1992年01月
  • Atrial natriuretic peptide reduces the basal level of cytosolic free Ca2+in guinea pig cardiac myocytes
    Masahiko Tei, Minoru Horie, Toshinori Makita, Hiroshi Suzuki, Akihiro Hazama, Yasunobu Okada, Chuichi Kawai
    Biochemical and Biophysical Research Communications 167 413-418 1990年03月
    The cytosolic free Ca 2+ concentration ([Ca 2+ ] i ) was monitored in quiescent atrial and ventricular myocytes isolated from guinea-pig hearts by the fura-2 fluorescence ratio technique. Recombinant human atrial natriuretic peptide (ANP) was found to reduce their basal [Ca 2+ ] i level in a dose-dependent manner. Dibutyryl-cGMP mimicked the effect of ANP. Neither the prior application of caffeine nor removal of extracellular Na + impaired the ANP effect. ANP had no inhibitory effect on voltage-gated Ca 2+ currents measured by a whole-cell patch clamp technique. The ANP-induced [Ca 2+ ] i decrease was abolished by orthovanadate. Thus, it is concluded that ANP reduces the basal [Ca 2+ ] i presumably through the cGMP-mediated activation of the plasma membrane Ca 2+ -pump in cardiac myocytes. © 1990.
  • Two types of delayed rectifying K+channels in atrial cells of guinea pig heart
    M. Horie, S. Hayashi, C. Kawai
    Japanese Journal of Physiology 40 479-490 1990年01月
  • On the Mechanism of β-adrenergic Activation of Cardiac Outward Currents : Chloride and Delayed Rectifier Potassium Conductance : Mechanism of intracellular regulation of cardiac ion channels and its abnormality
    堀江 稔, 牧田 俊則, 鈴木 浩, / 河合 忠一 /, Kawai Chuichi, Gadsby David C.
    JAPANESE CIRCULATION JOURNAL 56(0) 1344-1348 1993年
  • Voltage‐dependent magnesium block of adenosine‐triphosphate‐sensitive potassium channel in guinea‐pig ventricular cells.
    M. Horie, H. Irisawa, A. Noma
    The Journal of Physiology 387 251-272 1987年06月
    1. The adenosine‐5'‐triphosphate (ATP)‐sensitive K+ channel of guinea‐pig ventricular cells was examined in the presence and absence of internal Mg2+ or Na+ using an open cell‐attached configuration of the patch‐clamp technique. 2. Millimolar concentrations of internal Mg2+ ([Mg2+]i) produced marked fluctuations in the outward current, and the amplitude of the open‐channel current was reduced with increasing [Mg2+] i. Millimolar Na+ applied internally also decreased the mean amplitude of the outward current, but the increase in current noise was not obvious. These effects became larger when the membrane potential was shifted to be more positive from the K+ equilibrium potential (EK). At potentials negative to EK the inward current was affected by neither internal Mg2+ nor Na+. 3. The external application of Na+, Mg2+ or Ca2+, however, failed to affect the single‐channel current. 4. After removal of both internal Mg2+ and Na+, the mean open‐channel current‐voltage relationship became virtually linear. Referring to these unblocked values, relative amplitudes were determined at different levels of [Mg2+]i or [Na+] i. The dose‐response relations gave a Hill coefficient of approximately 1 for Mg2+ block and approximately 2 for Na+ block. The half‐maximum concentrations (Kh) for both Mg2+ and Na+ block were shifted to lower values with increasing positive potentials. 5. The power‐density spectrum of the open‐channel current noise induced by internal Mg2+ showed a Lorentzian function with a corner frequency above 1 kHz, suggesting that the current noise is due to rapid fluctuations of open‐channel current between blocked and unblocked states. The corner frequencies gave Mg2+ block and unblock rate constants which were of the order of 10(7) M‐1 s‐1 and 10(4) s‐1, respectively. 6. With increasing external K+ concentration ([K+] o) from 0 to 140 mM the current fluctuations became less prominent, and Kh for Mg2+ block was shifted to higher values. Raising [K+]o enhanced the unblock rate derived from the noise analysis while the block rate was not significantly altered. 7. The above findings could be explained by assuming a binding site for one Mg2+ or two Na+ located 30‐35% of the electrical drop across the membrane from the inner mouth of the channel, thereby resulting in the ionic block of K+ passage. An apparent inward rectification observed in the single‐channel current‐voltage relation is attributable to the blockade of the channel by intracellular Mg2+ and/or Na+. © 1987 The Physiological Society
  • 亜硝酸剤舌下投与では、軽減されずその冠動脈内注入により軽減された不安定狭心症の1例
    堀江 稔
    最新医学 37(12) 2458-2462 1982年12月
  • エプレレノン
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  • 新・心臓病診療プラクティス 3.心機能を識る : 心機能の液性調節機序
    文光堂 62-70 2004年
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    メジカルビュー社 80-90 2004年
  • 二重房室結節伝導路が上室性頻拍(SVT)形成に寄与した不顕性WPW症候群の1例
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    核医学 41(4) 459 2004年
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    核医学 41(3) 323 2004年
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    J Am Coll Cardiol 43(5) 363-364 2004年
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    松尾 信郎, 中村 保幸, 松本 鉄也, 中江 一郎, 洪 照恵, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 67(0) 2003年10月
  • 抗アルドステロン薬になにを期待するか--心臓はアルドステロンの標的臓器である (第1土曜特集 心不全のあらたな治療戦略) -- (治療の現状と戦略)
    蔦本 尚慶, 堀江 稔
    医学のあゆみ 206(10) 741-747 2003年09月
  • 右房腫瘤として発見され生検にて悪性リンパ腫と診断されたAIDSの1例(第95回日本循環器学会近畿地方会)
    宮本 証, 松尾 信郎, 中村 保幸, 中江 一郎, 松本 鉄也, 和田 厚幸, 伊藤 誠, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 67(0) 2003年10月
  • 不整脈と心筋イオンチャネル:QT延長症候群の分子基盤 (特集 チャネル・トランスポーターの分子医学2003)
    堀江 稔
    モレキュラ-メディシン 40(7) 802-808 2003年07月
  • アトピー性皮膚炎に黄色ブドウ球菌による感染性心内膜炎を併発し急激な大動脈弁破壊の経過をとった1例(第95回日本循環器学会近畿地方会)
    山路 正之, 高橋 正行, 環 愼二, 宮本 証, 大西 正人, 和田 厚幸, 松本 鉄也, 中村 保幸, 堀江 稔, 東田 隆治, 白石 昭一郎, 浅井 徹, 西山 敬三, 川嶋 剛史
    Circulation journal : official journal of the Japanese Circulation Society 67(0) 2003年10月
  • 薬物誘発性QT延長症候群 : 遺伝的素因を含めた患者背景
    堀江 稔
    日本薬理学雑誌 121(6) 401-407 2003年06月
    QT延長症候群(LQTS)は,心電図上,著しいQT時間の延長と心臓突然死に繋がる多形性心室頻拍(torsade de pointes)を起こす疾患群であり,古くより家族性に発症することが知られていたが,近年,分子遺伝学あるいは細胞電気生理学の進歩の結果,心筋の興奮·伝導を担うイオンチャネル遺伝子の変異により,LQTSが惹起されることが解明された.一方,日常診療では,たとえば,薬剤性を含む2次性LQTSの患者に遭遇することが多い.このような症例の一部にも遺伝的背景が発見されるようになってきた.現在までに判明している種々の変異は,遺伝性LQTS関連遺伝子の全般にわたって発見されている.その機能解析では,チャネルへの障害の程度が軽いものも存在する.したがって2次性LQTSも一部はイオンチャネル病であることが理解された.本稿では,今日までに報告された種々の2次性LQTSにおける遺伝子異常について紹介し概説する.
  • 重症不整脈とイオン・チャネル異常 (研究会 第3回九州重症不整脈研究会)
    堀江 稔
    臨牀と研究 80(6) 1145-1149 2003年06月
  • Hereditary Arrhythmia : From Gene to Clinics
    堀江 稔
    不整脈 = Journal of arrhythmia 19(2) 2003年04月
  • Genotype-phenotype Correlation in Brugada Syndrome
    堀江 稔
    不整脈 = Journal of arrhythmia 19(2) 2003年04月
  • 液性因子測定の意義-BNPの意義と限界
    内科 91 444-448 2003年
  • 抗アルドステロン薬になにを期待するか-心臓はアルドステロンの標的臓器である-
    医学のあゆみ 206 741-747 2003年
  • 37) 冠静脈洞内に留置したMP basket catheterがablationの通電部位決定に有用であった房室結節回帰頻拍の1例
    池口 滋, 天谷 直貴, 綿貫 正人, 河合 忠一, 堀江 稔
    Circulation journal : official journal of the Japanese Circulation Society 66(0) 2002年10月
  • 心不全の生化学診断 -BNPを中心に-
    日本臨床 61 782-788 2003年
  • 心筋Na^+チャネルの遺伝子変異(2.不整脈の遺伝・分子機構)(<特集>第66回日本循環器学会学術集会)
    蒔田 直昌, 神田 章弘, 渡辺 一郎, 堀江 稔
    循環器専門医 : 日本循環器学会専門医誌 10(2) 245-249 2002年10月
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    J Nucl Cardiol 10(1) S44-S44 2003年
  • アンジオテンシンの心筋イオンチャネルに対する作用
    堀江 稔
    心電図 = Electrocardiology 22(5) 2002年08月
  • イオンチャネル病と遺伝子診断(<特集>基礎医学の進歩)
    堀江 稔
    循環器専門医 : 日本循環器学会専門医誌 10(1) 13-20 2002年03月
  • ATP感受性K^+チャネル
    野間 昭典, 堀江 稔, 鷹野 誠
    日本内科学会雑誌 91(3) 865-867 2002年03月
  • 二次性QT延長症候群と遺伝子異常 (特集 不整脈研究の新しい潮流) -- (不整脈の基礎に関する新展開)
    堀江 稔
    医学のあゆみ 200(9) 667-672 2002年03月
  • 87) 房室結節回帰性頻拍と単形性心室期外収縮に対し, 遅伝達路アブレーションと大動脈弁左冠尖でのアブレーションを施行し, 両者を根治した1症例(日本循環器学会 第91回近畿地方会)
    天谷 直貴, 河合 忠一, 池口 滋, 綿貫 正人, 藍 智彦, 堀江 稔
    Japanese circulation journal 65(0) 2001年10月
  • 内科-100年のあゆみ(循環器) 日本人の貢献-ATP感受性Kチャネル
    日本内科学会誌 91 89-91 2002年
  • 46) Torsade de pointes で発症した産褥期心筋症の1例
    松岡 弘典, 大谷 秀夫, 当麻 正直, 吉田 秀忠, 堀江 稔, 松森 昭, 篠山 重威
    Japanese circulation journal 65(0) 2001年04月
  • QT延長症候群
    循環器疾患最新の治療2002-2003 343-346 2002年
  • カリウム・チャネル病の遺伝子診断と機能解析
    第5回アミオダロン研究会講演集 21 147-158 2001年
  • QT延長症候群における不整脈治療の特殊性とその理論
    Progress in Medicine 21 87-91 2001年
  • 植込み型除細動器(ICD)治療におけるアミオダロンの有用性と限界)
    Progress in Medicine  21 174-178 2001年
  • 細胞内灌流法
    新パッチクランプ実験技術法 125-137 2001年
  • QT延長症候群
    循環器研修医ノート 532-535 2001年
  • 心筋クロライド・チャネル
    Key Word 心臓病 166-167 2001年
  • 108) 孤発性QT延長症候群の1例
    原田 範雄, 堀江 英生, 渡辺 純二, 小久保 学, 松山 敏, 寺田 正樹, 鈴木 章八, 伊藤 文哉, 神谷 香一郎, 堀江 稔
    Japanese circulation journal 64(0) 2000年10月
  • 先天性QT延長症候群 「循環器疾患-state of arts」
    医学のあゆみ 591-593 2001年
  • 39) Hereditary motor and sensory neuropathyに合併した無症候性Brugada症候群の1例
    白樫 義知, 堀江 稔, 大谷 秀夫, 春名 徹也, 河野 裕, 吉田 秀忠, 久保田 友之, 篠山 重威, 池口 滋
    Japanese circulation journal 64(0) 2000年04月
  • 多彩な上室性不整脈およびgap現象を示した1例
    臨床心臓電気生理別冊 14 35-46 2001年
  • SIV-6 QT延長症候群のmolecular medicine : 遺伝子異常を基盤とした治療を求めて
    堀江 稔, 大谷 秀夫, 吉田 秀忠, 春名 徹也, 河野 裕, 久保田 友之, 二宮 智紀, 篠山 重威, 山下 文男, 相澤 義房, 鷹野 誠
    Japanese circulation journal 64(0) 2000年03月
  • 1052 KCNQ1 C末端のmissence mutationによるLQT1 : genotype-phenotype解析
    山下 文男, 相澤 義房, 堀江 稔, 久保田 友之, 吉田 秀忠, 篠山 重威
    Japanese circulation journal 64(0) 2000年03月
  • P497 細胞膜伸展刺激によるI_の増加のセンサーはKCNQ1で, チロシンリン酸化を必要としない
    久保田 友之, 堀江 稔, 吉田 秀忠, 二宮 智紀, 河野 裕, 春名 徹也, 大谷 秀夫, 篠山 重威, 鷹野 誠
    Japanese circulation journal 64(0) 2000年03月
  • P499 交感神経α1受容体刺激は、細胞膜PIP_2(phosphatidylinositol-4,5 bisphosphate) レベルの変動を介して, 細胞膜ATP感受性K^+チャネル (K_) チャネル活動を直接制御している
    春名 徹也, 堀江 稔, 河野 裕, 篠山 重威, 謝 来華, 鷹野 誠
    Japanese circulation journal 64(0) 2000年03月
  • P501 Verapamilによる心筋K_チャネル阻害の作用点は、チャネル孔を形成するKir6.2サブユニットである
    二宮 智紀, 堀江 稔, 春名 徹也, 河野 裕, 吉田 秀忠, 久保田 友之, 篠山 重威
    Japanese circulation journal 64(0) 2000年03月
  • QT延長症候群はどこまでわかったか
    Heart View 4 68-72 2000年
  • 特集 21世紀の分子医学-心血管病の克服をめざして-不整脈
    分子心血管病 1 31-36 2000年
  • 先天性QT延長症候群-チャネル病としての治療戦略
    集中治療 12 509-514 2000年
  • マグネシウムと虚血性心疾患
    マグネシウムと循環器疾患 4 9-14 2000年
  • Brugada症候群
    CARDIAC PRACTICE  12 105-108 2000年
  • 79)電気生理学的検査の検討が役立ったHERG遺伝子異常を認めるQT延長症候群(LQT2)の一例
    大道 近也, 藤井 英太郎, 寺村 忍, 内田 文也, 笠井 篤信, 中野 赳, 堀江 稔
    Japanese circulation journal 63(3) 1999年10月
  • 房室解離・異所性補充調律
    Practical Seminar不整脈 189-195 2000年
  • 91)左上肺静脈への高周波カテーテル・アブレーションが心房細動のコントロールに有用であった発作性心房細動の1例
    池口 滋, 綿貫 正人, 堀江 稔, 藍 智彦, 吉田 秀忠, 河野 祐, 春名 徹也, 篠山 重威
    Japanese circulation journal 63(3) 1999年10月
  • 家族性不整脈症候群の遺伝子解析
    目でみる循環器シリーズ1 「不整脈」 137-142 2000年
  • イオンチャネルとチャネル病 : I 循環器病学における生理学と分子生物学の融合(<特集>第63回日本循環器学会学術集会)
    堀江 稔
    循環器専門医 : 日本循環器学会専門医誌 7(2) 199-206 1999年10月
  • ジギタリスによる虚血プレコンディショニング修飾の機序 -細胞膜ATP感受性カリウム・チャネルの機能的連関-
    堀江 稔, 春名 徹也, 河野 裕, 吉田 秀忠, 縄田 隆三, 村上 知行, 篠山 重威
    心電図 = Electrocardiology 19(5) 1999年08月
  • 119)弁輪直下心室ペーシングによる潜在性副伝導路心室付着端の評価法
    池口 滋, 綿貫 正人, 竹岡 玲, 二宮 智紀, 白坂 明広, 北川 元昭, 田中 省三, 橋本 哲男, 堀江 稔, 西本 紀久, 藍 智彦, 吉田 秀忠, 河野 祐, 春名 徹也, 篠山 重威
    Japanese circulation journal 63(2) 1999年08月
  • 心不全における不整脈とその対策 (特集 不整脈の新展開--基礎から臨床まで) -- (不整脈の臨床・治療面の話題)
    堀江 稔
    医学のあゆみ 189(5) 349-353 1999年05月
  • PLI-2 イオン・チャネルとチャネル病
    堀江 稔, 大谷 秀夫, 吉田 秀忠, 河野 裕, 春名 徹也, 久保田 友之, 西本 紀久, 藍 智彦, 赤尾 昌治, 村上 知行, 鷹野 誠, 野間 昭典, 篠山 重威
    Japanese circulation journal 63(1) 1999年03月
  • 0219 イソプロテレノール負荷によるMAP持続時間の短縮がみられた新たなLQT2症例の電気生理学的特徴
    吉田 秀忠, 堀江 稔, 大谷 秀夫, 辻 啓子, 藍 智彦, 久保田 友之, 篠山 重威, 鷹野 誠, 河島 哲也, 大西 一男, 足立 和彦
    Japanese circulation journal 63(1) 1999年03月
  • 0277 QT延長症候群 : LQT1、LQT2に於けるQT時間の比較
    藍 智彦, 堀江 稔, 久保田 友之, 吉田 秀忠, 大谷 秀夫, 篠山 重威
    Japanese circulation journal 63(1) 1999年03月
  • 0568 心筋虚血後のKir6.1遺伝子発現増加による心筋保護効果の可能性 : Kir6.1タンデム蛋白による検討
    河野 裕, 堀江 稔, 大谷 秀夫, 赤尾 昌治, 村上 知行, 篠山 重威, 鷹野 誠
    Japanese circulation journal 63(1) 1999年03月
  • 0576 虚血関連物質l-palmitoylcarnitineは虚血時にphosphatidylbisphosphate(PIP_2)による心筋ATP感受性Kチャネルの開口維持を抑制する。
    春名 徹也, 堀江 稔, 西本 紀久, 篠山 重威
    Japanese circulation journal 63(1) 1999年03月
  • 0580 ラット心筋虚血モデルにおける心筋K_チャネル遺伝子の特異的発現と組織アンジオテンシンIIの役割
    赤尾 昌治, 村上 知行, 大谷 秀夫, 堀江 稔, 胡内 一郎, 篠山 重威
    Japanese circulation journal 63(1) 1999年03月
  • 0581 抗CD8抗体を用いた発現細胞の選別によるKvLQT1チャネル電流の解析
    久保田 友之, 堀江 稔, 吉田 秀忠, 河野 裕, 春名 徹也, 藍 智彦, 西本 紀久, 大谷 秀夫, 篠山 重威, 鷹野 誠
    Japanese circulation journal 63(1) 1999年03月
  • 嚢胞性線維症とCFTR
    最新医学  54 55-59 1999年
  • 心不全に於ける不整脈とその対策
    医学のあゆみ 189 349-353 1999年
  • QT延長症候群とは
    Cardiologist 9 636-640 1999年
  • イオンチャネルとチャネル病
    循環器専門医  7 199-214 1999年
  • 心電図から不整脈の発生機序はわかるか.