研究者業績

井澤 英夫

イザワ ヒデオ  (Hideo Izawa)

基本情報

所属
藤田医科大学 医学部 医学科 教授
学位
医学博士(名古屋大学)

J-GLOBAL ID
200901029584552340
researchmap会員ID
6000001679

学歴

 2

論文

 200
  • Reina Ozaki, Sadako Motoyama, Yukio Ozaki, Masayoshi Sarai, Hideki Kawai, Tevfik F. Ismail, Wakaya Fujiwara, Keiichi Miyajima, Yasuomi Nagahara, Noriya Uchida, Scot Garg, Naoyuki Kawashima, Yudai Niwa, Hidemaro Takatsu, Yu Yoshiki, Masaya Ohta, Takashi Muramatsu, Masahide Harada, Hiroyuki Naruse, Ayaka Matsui, Haruo Kamiya, Akihiko Tobe, Tsai Tsung-Ying, Yasuko Bando, Yoshinobu Onuma, Hiroshi Takahashi, Hideo Izawa, Patrick W. Serruys, Toyoaki Murohara
    International Journal of Cardiology 421 132895-132895 2025年2月  
  • Yu Yoshiki, Yukio Ozaki, Mitsuru Abe, Tevfik F Ismail, Hiroshi Takahashi, Masaharu Akao, Hideki Kawai, Takashi Muramatsu, Masahide Harada, Masaya Ohta, Yosuke Hashimoto, Yuichiro Shiki, Masayuki Koshikawa, Keiichi Miyajima, Hidemaro Takatsu, Yudai Niwa, Naoyuki Kawashima, Reina Ozaki, Naotake Tsuboi, Satoshi Iimuro, Hiroshi Iwata, Ichiro Sakuma, Yoshihisa Nakagawa, Kiyoshi Hibi, Takafumi Hiro, Yoshihiro Fukumoto, Seiji Hokimoto, Katsumi Miyauchi, Hisao Ogawa, Hiroyuki Daida, Hiroaki Shimokawa, Hideo Izawa, Takeshi Kimura, Ryozo Nagai
    Journal of the American Heart Association 14(2) e034627 2025年1月21日  
    BACKGROUND: The effect of worsening renal function and baseline chronic kidney disease (CKD) on outcomes in patients with chronic coronary syndrome in the setting of optimal medical therapy remains unknown. METHODS AND RESULTS: The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease) study is a prospective, multicenter, randomized trial of high-dose (pitavastatin 4 mg/day) or low-dose (pitavastatin 1 mg/day) statin therapy in 12 118 patients with chronic coronary syndrome. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, stroke, or unstable angina requiring hospitalization (major adverse cardiac and cerebral events [MACCE]). CKD was defined as an estimated glomerular filtration rate [eGFR] <60 mL/min per 1.73 m2. WRF was defined as a decrease in eGFR ≥20% in the initial year; borderline renal function was an annual decrease of 0%<eGFR<20%, and stable renal function was no decrease. Of 12 118 patients, 4340 had baseline CKD and 7778 did not. The rate of MACCE at 5 years was significantly lower in those without (5.5%) versus with CKD (9.5%) (P<0.0001). After excluding 1247 patients who had MACCE, were censored, or missing eGFR within 1 year, 10 871 patients were included. Of these, 3885 were baseline CKD and the remaining 6986 did not have baseline CKD. Of the 10 871 patients, 577 patients had WRF, 6014 patients showed borderline renal function, and the remaining 4280 patients maintained stable renal function. In patients with CKD, WRF was an independent predictor for MACCE at 4 years as compared with stable renal function (hazard ratio [HR]: 1.67; [95% CI, 1.03-2.73; P=0.039]). In patients without CKD, borderline renal function was a significant predictor for MACCE at 4 years compared with stable renal function (HR: 1.40 [95% CI, 1.03-1.91; P=0.032]). CONCLUSIONS: Baseline CKD was an independent predictor for MACCE in patients with CCS. WRF was a significant predictor for MACCE in patients with CKD. Because borderline renal function was an independent predictor for MACCE even in patients without CKD, mild-to-moderate annual declines of eGFR should be carefully monitored (NCT01042730). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01042730.
  • Yuji Kono, Masahiko Mukaino, Yushi Ozawa, Koji Mizutani, Yuki Senju, Takayuki Ogasawara, Masumi Yamaguchi, Takashi Muramatu, Hideo Izawa, Yohei Otaka
    Heart and vessels 39(10) 918-919 2024年10月  
  • Taro Makino, Yuya Ishihara, Masahide Harada, Yoshihiro Sobue, Eiichi Watanabe, Yukio Ozaki, Hideo Izawa
    International Heart Journal 65(5) 841-848 2024年9月30日  
  • Masataka Yoshinaga, Takashi Muramatsu, Masato Ishikawa, Takuo Toriya, Takashi Uwatoko, Yuji Matsuwaki, Yuko Ukai, Yohei Kobayashi, Katsuyoshi Ito, Hideaki Ota, Hideo Izawa
    Cardiovascular intervention and therapeutics 2024年8月13日  
    Slow-flow or no-reflow phenomenon is a common procedural complication during percutaneous coronary intervention (PCI). Given the presence of fragile plaque or thrombotic materials, we hypothesized that long-time predilatation using a perfusion balloon in conjunction with intracoronary nicorandil administration reduces the risk of slow-flow or no-reflow in patients presenting with acute coronary syndrome (ACS). Subjects were patients presenting with ACS who underwent PCI between April 2020 and April 2022. We retrospectively investigated the incidence of slow-flow or no-reflow during the procedure as well as in-hospital outcomes in comparison between the cases undergoing 3-min predilatation using a perfusion balloon in conjunction with intracoronary nicorandil administration followed by DES implantation (PB group) and those with direct stenting (DS group). Among 439 ACS patients, 36 patients in the PB group and 51 patients in the DS group were examined. Mean age was 70 years and 78.2% was male. Distal protection devices were more frequently used in the DS group than in the PB group (31.3% vs. 11.1%, p = 0.02). The incidence rate of slow-flow or no-reflow was significantly lower in the PB group than in the DS group (2.8% vs. 23.5%; p < 0.01). Six cases (11.7%) in the DS group required intra-aortic balloon pumping (IABP), while none in the PB group required (p < 0.01). In-hospital clinical outcomes did not differ between the two groups. Prolonged perfusion balloon predilatation in conjunction with intracoronary nicorandil administration was safe and feasible. This novel strategy could be an attractive alternative to conventional direct stenting for ACS patients.

MISC

 273
  • TS Kato, A Yamada, A Noda, H Izawa, Y Murase, K Yamada, H Asano, M Iwase, M Yokota
    CIRCULATION 110(17) 551-551 2004年10月  
  • H Izawa, Y Murase, JL Xu, H Asano, T Kato, A Yamada, S Isobe, S Ohshima, K Yamada, Y Inden, K Okumura, T Murohara
    CIRCULATION 110(17) 479-480 2004年10月  
  • 山田 晶, 因田 恭也, 加藤 倫子, 柴田 義久, 武藤 真広, 野田 浩範, 高田 康信, 井澤 英夫, 近藤 隆久, 室原 豊明, 野田 明子, 平井 真理, 伊藤 理恵子, 横田 充弘, 吉川 雅治, 澤木 完成, 竹中 拡晴, 碓氷 章彦, 上田 裕一
    Therapeutic Research 25(10) 2034-2038 2004年10月  
  • Akira Yamada, Sahoko Ichihara, Yosuke Murase, Tomoko Kato, Hideo Izawa, Kohzo Nagata, Toyoaki Murohara, Yoshiji Yamada, Mitsuhiro Yokota
    Journal of Molecular Medicine 82(7) 477-483 2004年7月  
    Vascular inflammation plays an important role in the development of myocardial infarction (MI). Lymphotoxin α (LTA) is a cytokine with multiple functions in regulation of the immune system and inflammatory reactions. The aim of this study was to examine whether polymorphisms of the LTA gene are associated with the risk of MI in Japanese men and women. A case-control association study was performed for the 252A→G and 804C→A polymorphisms of the LTA gene and the prevalence of MI. The study population comprised 3,689 unrelated Japanese individuals (2,486 men, 1,203 women), including 1891 patients with MI (1,493 men, 398 women) and 1798 control subjects (993 men, 805 women). Among the control subjects 257 individuals (108 men, 149 women) who had none of the conventional risk factors for coronary artery disease (CAD) were defined as low-risk controls. Genotypes for the two polymorphisms were determined with a fluorescence-based allele-specific DNA primer assay system. Among all study subjects the 252A→G and 804C→A polymorphisms exhibited linkage disequilibrium. No association of either polymorphism with MI was detected in men or in women in comparisons with total control or low-risk control subjects. However, each of the two polymorphisms was associated with the prevalence of type 2 diabetes mellitus both in men with MI and in those without MI in a recessive genetic model. No association was detected between the polymorphisms and other conventional risk factors for CAD. The LTA gene thus does not appear to be a susceptibility locus for MI in Japanese men or women, although it might affect susceptibility to type 2 diabetes in Japanese men. © Springer-Verlag 2004.
  • H Horibe, Y Yamada, S Ichihara, M Watarai, M Yanase, K Takemoto, S Shimizu, H Izawa, F Takatsu, M Yokota
    ATHEROSCLEROSIS 174(1) 181-187 2004年5月  
    Plain old balloon angioplasty (POBA) is a useful therapeutic strategy especially for angioplasty of small coronary arteries. An association study was performed to identify genes that confer susceptibility to restenosis after POBA. The study population comprised 730 individuals (424 men, 306 women) who underwent successful POBA in at least one major coronary artery and were examined angiographically 6 months after the procedure. A total of 469 subjects (273 men, 196 women) exhibited no restenosis after POBA for any of the coronary lesions, whereas 261 subjects (151 men, 110 women) manifested restenosis for all lesions. The genotypes for 40 polymorphisms of 34 genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia revealed that two polymorphisms (242C --&gt; T in the NADH/NADPH oxidase p22 phox (p22-PHOX) gene and 2136C --&gt; T in the thrombomodulin (THBD) gene) in men and two polymorphisms (584G --&gt; A in the paraoxonase 1 (PON1) gene and 2445G --&gt; A in the fatty acid-binding protein 2 (FABP2) gene) in women were significantly associated with restenosis after POBA. A stepwise forward selection procedure revealed that the effects of these polymorphisms on restenosis were statistically independent of conventional risk factors for coronary artery disease. Genotyping of these polymorphisms may prove informative for assessment of genetic risk for restenosis after POBA. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
  • Y Yamada, S Ichihara, H Izawa, M Tanaka, M Yokota
    MOLECULAR GENETICS AND METABOLISM 81(4) 282-290 2004年4月  
    Given that a substantial proportion of individuals with coronary artery disease (CAD) also have type 2 diabetes, it is important to identify genes that confer susceptibility to CAD independently in subjects with type 2 diabetes and in those without this condition. A large-scale association study was performed to identify genes that confer susceptibility to CAD in either the absence or presence of type 2 diabetes. The study population comprised 5207 unrelated Japanese individuals, including 3085 subjects with CAD and 2122 controls. Among all subjects, 1704 individuals had type 2 diabetes and 3503 individuals did not have this condition. The genotypes for 33 polymorphisms of 27 candidate genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, hypertension, hypercholesterolemia, and hyperuricemia revealed that the following polymorphisms were significantly (P &lt; 0.005) associated with CAD: the 1019C &RARR; T of the connexin 37 gene for men with type 2 diabetes; the 2445G &RARR; A in the fatty acid-binding protein 2 gene for women with this condition; the -863C &RARR; A in the tumor necrosis factor-&alpha; gene, the -219G &RARR; T in the apolipoprotein E gene, the 1019C &RARR; T in the connexin 37 gene for men without type 2 diabetes; and the -482C &RARR; T in the apolipoprotein C-III gene for women without this condition. Genotyping of these polymorphisms may prove informative for assessment of the genetic risk for CAD in the absence or presence of type 2 diabetes. (C) 2004 Elsevier Inc. All rights reserved.
  • Xu Jinglan, Nagata Kohzo, Obata Koji, Ichihara Sahoko, Noda Akiko, Izawa Hideo, Iwase Mitsunori, Murohara Toyoaki, Yokota Mitsuhiro
    Circulation journal : official journal of the Japanese Circulation Society 68 535-535 2004年3月1日  
  • Kato Tomoko, Izawa Hideo, Yamada Akira, Murase Yosuke, Noda Akiko, Takada Yasunobu, Shibata Yoshihisa, Iwase Mitsunori, Murohara Toyoaki, Yokota Mitsuhiro
    Circulation journal : official journal of the Japanese Circulation Society 68 627-627 2004年3月1日  
  • J Cardiol 43 92-93 2004年  
  • 井澤 英夫, 近藤 隆久, 山本 晃士, 高松 純樹, 古森 公浩, 室原 豊明
    内科 94(2) 339-342 2004年  
  • M Iwase, H Kanazawa, Y Kato, T Nishizawa, F Somura, R Ishiki, K Nagata, K Hashimoto, K Takagi, H Izawa, M Yokota
    CARDIOVASCULAR RESEARCH 61(1) 30-38 2004年1月  
    Objective: The mammalian heart contains specific growth hormone-releasing peptide (GHRP) binding sites whose physiological significance is unknown. We sought to compare the effects of GHRP and GH on progressive left ventricular (LV) dysfunction in the TO-2 hamster model of dilated cardiomyopathy. Methods: TO-2 hamsters (8 weeks old) were injected with GHRP-6 (100 mug/kg day), GH (2 mg/ kg day), or saline for 4 weeks; F1B hamsters served as controls. LV functional and structural changes were evaluated by echocardiography and pathology. Results: The increase in body weight of GH-treated TO-2 hamsters was greater than that of animals in the other two groups. Plasma GH and insulin-like growth factor-1 (IGF-1) concentrations were not increased by GHRP-6. LV fractional shortening (LVFS) decreased from 42.0 +/- 2.6% to 25.4 +/- 1.8% and the LV end-diastolic dimension (LVDd) increased from 4.0 +/- 0.1 to 5.0 +/- 0.1 mm in untreated TO-2 hamsters between 8 and 12 weeks. LVFS was substantially improved by treatment with GHRP-6 (33.4 +/- 2.0%) or GH (32.0 +/- 2.1%). The LVDd was significantly smaller in animals treated with GHRP-6 than in those treated with GH. The cross-sectional LV myocyte area and the amount of atrial natriuretic peptide mRNA in the LV were increased by GH but not by GHRP-6. Treatment woth GH at a lower dose (0.2 mg/(kg day)) exerted minimal cardiac and systematic growth effects without improving LV function. Conclusion: GHRP can ameliorate the development of progressive LV dysfunction independently of the GH-IGF-1 axis, suggesting a potential new approach to the heart failure. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
  • K Shimokata, Y Yamada, T Kondo, S Ichihara, H Izawa, K Nagata, T Murohara, M Ohno, M Yokota
    ATHEROSCLEROSIS 172(1) 167-173 2004年1月  
    A substantial proportion of individuals with coronary artery disease (CAD) has concomitant hypercholesterolemia. A large-scale association study was performed to identify separately genes that confer susceptibility to CAD in the absence or presence of nonfamilial hypercholesterolemia. The study population comprised 5248 unrelated Japanese individuals, including 3085 subjects with CAD (2350 men, 735 women) and 2163 controls (1329 men. 834 women). Among all study subjects, 2541 individuals (1688 men, 853 women) had nonfamilial hypercholesterolemia, and 2707 individuals (1991 men, 716 women) did not have this condition. The genotypes for 33 polymorphisms of 27 candidate genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hyperuricemia revealed that three polymorphisms [994G --&gt; T (Va1279Phe) in the platelet-activating factor acetylhydrolase gene, 242C --&gt; T (His72Tyr) in the NADH/NADPH oxidase p22 phox gene, and 1100C --&gt; T in the apolipoprotein C-III gene] were significantly associated with CAD in men with hypercholesterolemia. Genotyping of these three polymorphisms may prove informative for prediction of the genetic risk for CAD in men with nonfamilial hypercholesterolemia. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
  • H Umeda, M Iwase, H Kanda, H Izawa, K Nagata, R Ishiki, K Sawada, T Murohara, M Yokota
    AMERICAN HEART JOURNAL 147(1) 145-152 2004年1月  
    Background Small vessel size represents a critical risk factor for an adverse outcome after both conventional balloon angioplasty (POBA) and stenting. Gradual and prolonged balloon angioplasty (GPBA) has been shown to cause less arterial trauma, which results in higher procedural success rates and fewer in-hospital complications than POBA. The aim of this study was to assess the clinical and angiographic benefits of primary GPBA with a perfusion balloon in small coronary arteries, as compared with cutting balloon angioplasty (CBA) and POBA. Methods A total of 263 patients with symptoms and reference diameters &lt;3.0 mm were randomly assigned to undergo GPBA (n = 85), CBA (n = 88), or POBA (n = 90). The cumulative inflation time must be &gt; 10 minutes in GPBA. Crossover to stent was allowed for inadequate results. Follow-up angiography was performed after 6 months. The primary end point was angiographic restenosis at follow-up. Results Compared with POBA, GPBA resulted in a lower final residual diameter stenosis (27.3% vs 34.2%, P = .01) and decreased the need for stent placement (8.0% vs 22.2%, P = .031). At follow-up, the restenosis rates were lower with GPBA (31.3%, P = .034) and CBA (32.9%, P = .059) than POBA (50.6%). Target lesion revascularization was less frequently needed with GPBA (20.5%, P = .043) and CBA (20.0%, P = .033) than POBA (37.6%). Additionally, the event-free survival rate was higher with GPBA (77.1%, P = .033) and CBA (76.4%, P = .047) than POBA (58.8%). Conclusions in small coronary arteries, both GPBA and CBA resulted in favorable angiographic and clinical outcomes. With a lower restenosis rate and target lesion revascularization rate, GPBA may be a superior strategy for small vessels compared with POBA.
  • K Nagata, K Obata, M Odashima, A Yamada, F Somura, T Nishizawa, S Ichihara, H Izawa, M Iwase, A Hayakawa, T Murohara, M Yokota
    JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 35(12) 1505-1512 2003年12月  
    The anti-anginal drug nicorandil has been shown to inhibit apoptosis by activating mitochondrial ATP-sensitive potassium (K-ATP) channels. The possible contribution of the nitrate moiety of this drug to its anti-apoptotic effect has now been investigated in neonatal rat ventricular myocytes subjected to oxidative stress. Exposure of cultured myocytes to 100 mumol/l hydrogen peroxide (H2O2) increased the number of nuclei stained by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling technique as well as induced internucleosomal DNA fragmentation, loss of mitochondrial membrane potential, cytochrome c release into the cytosol, and activation of caspases-3 and -9, all of which are characteristics of apoptosis. Pretreatment of cells with nicorandil (100 mumol/l) inhibited these effects of H2O2. Both the mitochondrial K-ATP channel antagonist 5-hydroxydecanoate (5-HD) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), an inhibitor of soluble guanylyl cyclase, attenuated the anti-apoptotic effect of nicorandil in concentration-dependent manners. Coapplication of ODQ (10 mumol/l) and 5-HD (500 mumol/l) completely abolished nicorandil-induced cytoprotection. The effect of nicorandil was also reduced by an inhibitor of cGMP-dependent protein kinase (KT5823, 1 mumol/l). The nitric oxide donor (+/-)-S-nitroso-N-acetylpenicillamine (SNAP, 50 mumol/l) mimicked the protective effect of nicorandil in a manner sensitive to ODQ but not to 5-HD. A cell-permeable cGMP analog, 8-bromo-cGMP. also reduced H2O2-induced apoptosis. The inhibition of the H2O2-induced activation of caspase-3, but not that of caspase-9, by nicorandil in the presence of 5-HD or by SNAP was reversed by the addition of dithiothreitol to the enzyme assay. Nicorandil inhibits oxidative stress-induced apoptosis in cardiac myocytes through a nitric oxide/cGMP-dependent mechanism as well as by activating mitochondrial K-ATP channels. (C) 2003 Elsevier Ltd. All rights reserved.
  • S Isobe, H Izawa, Y Takeichi, M Nonokawa, M Nanasato, A Ando, K Kato, M Ikeda, T Murohara, M Yokota
    JOURNAL OF NUCLEAR MEDICINE 44(11) 1717-1724 2003年11月  
    Many studies have demonstrated that reduced left ventricular (LV) diastolic distensibility plays a key role in the pathophysiology of hypertrophic cardiomyopathy (HCM). However, the relationship between myocardial ischemia and reduced LV distensibility in HCM remains unclear. We aimed to clarify the relationship between exercise-induced ischemia and reduced LV distensibility in patients with HCM. Methods: Twenty patients with HCM and 5 age-matched control subjects underwent stress-redistribution Tl-201 myocardial scintigraphy and biventricular cardiac catheterization and echocardiography at rest and during exercise. Scintigraphic defect analysis was interpreted using Berman's 20-segment model. The summed stress score (SSS) was calculated as the sum of scores of the 20 LV segments and the summed difference score (SDS) was calculated as the sum of differences between each of the 20 LV segments on stress and rest images. Results: Patients were divided into 2 groups according to the Tl-201 defect as follows: 9 patients with an SSS on Tl-201 of greater than or equal to10 and an SDS on Tl-201 of greater than or equal to5 (ischemic group) and 11 patients with an SSS of &lt;10 or an SDS of &lt;5 (nonischemic group). The absolute increases from rest to peak exercise in LV end-diastolic pressure (LVEDP) and pulmonary artery wedge pressure were significantly greater (15.5 +/- 5.2 vs. 7.6 +/- 5.5 mm Hg and 17.3 +/- 5.0 vs. 8.9 +/- 5.0 mm Hg, P &lt; 0.01, respectively), and the percentage changes from rest to peak exercise in the maximum first derivative of LV pressure and LV pressure half-time were significantly smaller in the ischemic HCM group compared with the nonischemic HCM group (70% +/- 24% vs. 123% +/- 43% and -32% +/- 6.4% vs. -44% +/- 9.4%, P &lt; 0.01, respectively). However, the end-diastolic dimensions did not differ between the 2 HCM groups. One of the 9 patients in the ischemic group, as revealed by fill-in on Tl-201 scintigraphy, showed increased F-18-FDG uptake in the anteroseptal wall. Conclusion: Some HCM patients show a significant increase in LVEDP without chamber dilatation, indicating reduced LV diastolic distensibility. Myocardial ischemia may at least in part contribute to this condition.
  • 加藤 倫子, 横田 充弘, 野田 明子, 岩瀬 三紀, 山田 晶, 井澤 英夫, 曽村 富士, 村瀬 洋介, 野々川 信, 因田 恭也, 飯野 重夫, 近藤 隆久, 高田 康信, 武市 康志, 永田 浩三, 室原 豊明
    Circulation journal : official journal of the Japanese Circulation Society 67 941-941 2003年10月20日  
  • 山田 晶, 井澤 英夫, 曽村 富士, 村瀬 洋介, 武市 康志, 室原 豊明, 野田 明子, 加藤 倫子, 西澤 孝夫, 横田 充弘, 青木 敏夫
    Circulation journal : official journal of the Japanese Circulation Society 67 952-952 2003年10月20日  
  • S Isobe, A Ando, M Nanasato, M Nonokawa, H Izawa, T Sobue, M Hirai, K Ito, T Ishigaki, T Murohara, M Yokota
    NUCLEAR MEDICINE COMMUNICATIONS 24(10) 1071-1080 2003年10月  
    This study aimed to determine whether combined examinations of myocardial 2-[F-18]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) and stress-redistribution Tl-201 single-photon emission computed tomography (Tl SPECT) were useful in clarifying myocardial ischaemia and evaluating the prognosis in patients with idiopathic dilated cardiomyopathy (IDCM). Twenty-two patients with IDCM underwent echocardiography, cardiac catheterization, FDG PET, and Tl SPECT. In scintigraphic analysis, the total defect score (TDS) was semiquantitatively determined as the sum of scores of the 17 left ventricular (LV) segments with a 5-point scale (0 as normal to 4 as absent). Patients were classified according to the scintigraphic findings as follows: eight patients with small defects on Tl and FDG (TDS less than or equal to 20) (group I), eight patients with small defects on FDG (TDS less than or equal to 20) with FDG uptake increased relative to Tl or 'mismatch' (group II), and six patients with large defects on FDG and Tl (TDS &gt; 20) (group III). Eleven patients (50%) showed reversible defects on Tl and all showed preserved FDG uptake. The patients in group III had significantly lower LV ejection fraction (LVEF) (P &lt; 0.05, respectively) and a poorer prognosis as shown by the Kaplan-Meier event-free curve compared with those in groups I and II (P &lt; 0.01, respectively). Although patients in group II had significantly greater TDS on Tl compared with those in group I (P &lt; 0.01), no significant differences in LVEF and prognosis were found between patients in groups I and II. In multivariate analysis, a TDS on FDG revealed an independent predictor of subsequent cardiac events. In conclusion, such mismatched areas can be assumed to consist of impaired but viable myocardium, and may be associated with ischaemia of the microvasculature. Impaired myocardial glucose metabolism is a more powerful predictor of future cardiac events than perfusion abnormality in patients with IDCM. ((C) 2003 Lippincott Williams & Wilkins).
  • H Umeda, M Iwase, H Izawa, T Nishizawa, M Nonokawa, S Isobe, A Noda, K Nagata, H Ishihara, M Yokota
    AMERICAN HEART JOURNAL 146(1) 75-83 2003年7月  
    Background Relaxation-frequency relations (RFR) during demand ischemia have not been fully examined in patients with effort angina pectoris (AP). We sought to clarify the effects of pacing and exercise on RFR in patients with AP. Methods We recorded left ventricular (LV) pressures during rapid atrial pacing and symptom-limited supine bicycle exercise. RFR were analyzed in 24 patients with AP and 10 controls. Results LV pressure half-time (T-1/2) in controls was gradually shortened with an increase in heart rate (HR) during pacing (-19% +/- 6% at peak HR). The changes in T-1/2 during pacing were biphasic with initial shortening (-12% +/- 5% at the critical HR) followed by prolongation (-3% +/- 7% at peak HR) in all patients with AP. The critical HR, at which T-1/2 was minimum, preceded the HR at 0.1-mV ST-segment depression, and finally chest pain occurred. The critical HR was correlated negatively with the severity of ischemia as assessed by thallium-201 scintigraphy. T-1/(2) was remarkably shortened during exercise in controls (-41% - 10% at peak exercise). In patients with AP, 2 distinct patterns of RFR were observed during exercise. T-1/2 was shortened progressively (-37% +/- 8% at peak exercise) in 15 patients, whereas RFR remained biphasic (-21% +/- 10% at the critical HR and - 11% +/- 11% at peak exercise) in the other 9 patients. Coronary angiography and exercise scintigraphy suggested more severe ischemia in patients with biphasic RFR during exercise. Conclusions Impaired RFR might be the most sensitive parameter of pacing-induced ischemia. The critical HR was closely related with severity of ischemia. Adverse effects of ischemia on IV relaxation may be alleviated by exercise.
  • H Izawa, M Iwase, Y Takeichi, F Somura, K Nagata, T Nishizawa, A Noda, T Murohara, M Yokota
    EUROPEAN HEART JOURNAL 24(14) 1340-1348 2003年7月  
    Aims Impaired coronary microcirculation is thought to contribute to myocardial ischaemia, causing an abnormal increase in left ventricular end-diastolic pressure during exercise in individuals with hypertrophic cardiomyopathy. The effects of nicorandil on left ventricular end-diastolic pressure during exercise were examined in patients with this condition. Methods and results Left ventricular pressures and dimensions were measured simultaneously during supine bicycle exercise in 23 patients with nonobstructive hypertrophic cardiomyopathy, before and after intravenous injection of either nicorandil (0.1 mg/kg) or propranolol (0.15 mg/kg). Exercise thallium-201 scintigraphy was also performed. Patients were grouped according to the changes in left ventricular end-diastolic pressure during exercise before treatment. Group I comprised 13 patients in whom left ventricular end-diastolic pressure increased progressively to abnormal values during exercise; group 11 comprised 10 patients in whom left ventricular end-diastolic pressure changed biphasically. The extents of both left ventricular hypertrophy and ischemic burden during exercise were greater in group I than in group II. Of the eight group I patients who received nicorandil, four individuals exhibited biphasic changes in left ventricular end-diastolic pressure during exercise after its administration whereas four subjects showed no such effect of the drug. Left ventricular end-diastolic pressure increased progressively during exercise after propranolol treatment in all 6 group II patients given this drug. Conclusion Nicorandil has a salutary effect on the changes in left ventricular end-diastolic pressure during exercise in patients with hypertrophic cardiomyopathy. (C) 2003 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
  • T Kato, A Noda, H Izawa, T Nishizawa, F Somura, A Yamada, K Nagata, M Iwase, A Nakao, M Yokota
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 42(2) 278-285 2003年7月  
    ORJECTIVES We investigated the utility of the peak negative myocardial velocity gradient (MVG) derived from tissue Doppler imaging (TDI) for evaluation of diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND Hypertrophic cardiomyopathy is characterized by impaired diastolic function with abnormal stiffness and prolonged relaxation. However, it remains difficult to evaluate these defects noninvasively. METHODS Both TDI and conventional echocardiography were performed in 36 patients with HCM and in 47 control subjects. Left ventricular (LV) pressure was measured simultaneously in all HCM patients and in 26 controls. RESULTS The peak negative MVG occurred soon after the isovolumic relaxation period during the initial phase of rapid filling (auxotonic relaxation). It was significantly smaller in HCM patients than in control subjects (2.32 +/- 0.52/s vs. 4.82 +/- 1.15/s, p &lt; 0.0001); the cutoff value for differentiation between all HCM patients and 47 normal individuals was determined as 3.2/s. Both the left ventricular end-diastolic pressure (LVEDP) (19.6 +/- 6.1 mm Hg vs. 6.5 +/- 1.7 mm Hg, p &lt; 0.0001) and the time constant of LV pressure decay during isovolumic diastole (tau) (44.0 +/- 6.7 ms vs. 32.1 +/- 5.5 ms, p &lt; 0.0001) were increased in HCM patients compared with controls. The peak negative MVG was negatively correlated with both LVEDP (r = -0.75, p &lt; 0.0001) and tau (r = -0.58, p &lt; 0.0001). CONCLUSIONS A reduced peak negative MVG reflects both prolonged relaxation and elevated LVEDP. The peak negative MVG might thus provide a noninvasive index of diastolic function, yielding unique information about auxotonic relaxation in patients with HCM. (C) 2003 by the American College of Cardiology Foundation.
  • H Izawa, Y Yamada, T Okada, M Tanaka, H Hirayama, M Yokota
    HYPERTENSION 41(5) 1035-1040 2003年5月  
    Although genetic epidemiological studies have suggested that several genetic variants increase the risk for hypertension, the genes that underlie genetic susceptibility to this condition remain to be identified definitively. Large-scale association studies that examine many gene polymorphisms simultaneously are required to predict genetic risk for hypertension. The population of the present study comprised 1940 unrelated Japanese individuals, including 1067 subjects with hypertension (574 men, 493 women) and 873 controls (533 men, 340 women). The genotypes for 33 single nucleotide polymorphisms of 27 candidate genes were determined with a fluorescence- or colorimetry-based allele-specific DNA primer-probe assay system. Multivariate logistic regression analysis with adjustment for age, body mass index, and the prevalence of smoking, diabetes mellitus, hypercholesterolemia, and hyperuricemia revealed that 2 polymorphisms (825C--&gt;T in the G protein beta3 subunit gene and 190G--&gt;A in the CC chemokine receptor 2 gene) were significantly associated with hypertension in men and that one polymorphism (-238G--&gt;A in the tumor necrosis factor alpha gene) was significantly associated with hypertension in women. These results suggest that 2 and 1 genes may be susceptibility loci for hypertension in Japanese men and women, respectively, and that genotyping of these polymorphisms may prove informative for prediction of the genetic risk for hypertension.
  • S Isobe, A Ando, M Nonokawa, M Nanasato, Y Takada, H Izawa, K Kato, M Ikeda, T Murohara, M Yokota
    JOURNAL OF NUCLEAR MEDICINE 44(5) 195P-195P 2003年5月  
  • 西澤 孝夫, 加藤 倫子, 横田 充弘, 野田 明子, 岩瀬 三紀, 山田 晶, 曽村 富士, 井澤 英夫, 磯部 智, 野々川 信, 永田 浩三, 室原 豊明
    Circulation journal : official journal of the Japanese Circulation Society 67 799-799 2003年4月20日  
  • Nagata Kohzo, Somura Fuji, Obata Koji, Yamada Akira, Izawa Hideo, Ichihara Sahoko, Iwase Mitsunori, Yamada Yoshiji, Murohara Toyoaki, Yokota Mitsuhiro
    Circulation journal : official journal of the Japanese Circulation Society 67 144-145 2003年3月1日  
  • H Izawa, Y Yamada, H Horibe, T Kato, S Ichihara, F Takatsu, T Murohara, M Yokota
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 41(6) 44A-44A 2003年3月  
  • 近藤 隆久, 井澤 英夫, 小林 昌義, 山本 晃士, 恵美 宣彦, 直江 知樹, 古森 公浩, 室原 豊明
    Geriat Med 41(12) 1819-1823 2003年  
  • 井澤 英夫, 曽村 富士, 山田 晶, 永田 浩三, 西澤 孝夫, 武市 康志, 梅田 久視, 磯部 智, 野々川 信, 因田 恭也, 近藤 隆久, 野田 明子, 岩瀬 三紀, 室原 豊明, 横田 充弘
    心臓 35(2) 58-60 2003年  
  • 梅田 久視, 岩瀬 三紀, 井澤 英夫, 永田 孝三, 室原 豊明, 横田 充弘
    心臓 35(2) 33-35 2003年  
  • 近藤 隆久, 井澤 英夫, 小林 昌義, 山本 晃士, 恵美 宣彦, 直江 知樹, 古森 公浩, 室原 豊明
    Geriat Med 41(12) 1819-1823 2003年  
  • Y Yamada, H Izawa, S Ichihara, F Takatsu, H Ishihara, H Hirayama, T Sone, M Tanaka, M Yokota
    NEW ENGLAND JOURNAL OF MEDICINE 347(24) 1916-1923 2002年12月  
    Background: Although epidemiologic studies have suggested that several genetic variants increase the risk of myocardial infarction, large-scale association studies that examine many polymorphisms simultaneously are required to allow reliable prediction of the genetic risk of myocardial infarction. Methods: We used a fluorescence- or colorimetry-based allele-specific DNA-primer-probe assay system to determine the genotypes of 112 polymorphisms of 71 candidate genes in 2819 unrelated Japanese patients with myocardial infarction (2003 men and 816 women) and 2242 unrelated Japanese controls (1306 men and 936 women). Results: In an initial screening of the 112 polymorphisms for an association with myocardial infarction in 909 subjects, 19 polymorphisms were selected in men and 18 in women by means of logistic-regression analysis, after adjustment for age, body-mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia. In a large-scale study involving the selected polymorphisms and the remaining 4152 subjects, similar logistic-regression analysis revealed that the risk of myocardial infarction was significantly associated with the C1019T polymorphism in the connexin 37 gene (P&lt;0.001) in men and the 4G-668/5G polymorphism in the plasminogen-activator inhibitor type 1 gene (P&lt;0.001) and the 5A-1171/6A polymorphism in the stromelysin-1 gene (P&lt;0.001) in women. Conclusions: Determination of the genotypes of the connexin 37, plasminogen-activator inhibitor type 1, and stromelysin-1 genes may prove reliable in predicting the genetic risk of myocardial infarction and might thus contribute to the primary prevention of this condition.
  • Y Yamada, H Izawa, S Ichihara, F Takatsu, H Ishihara, H Hirayama, T Sone, M Tanaka, M Yokota
    CIRCULATION 106(19) 745-745 2002年11月  
  • F Somura, A Hirashiki, H Umeda, IS Kim, Y Takeichi, T Nishizawa, H Izawa, A Noda, K Nagata, M Iwase, M Yokota
    CIRCULATION 106(19) 566-567 2002年11月  
  • 西澤 孝夫, 横田 充弘, 野田 明子, 岩瀬 三紀, 山田 晶, 曽村 富士, 井澤 英夫, 永田 浩三, 石川 真一
    Circulation journal : official journal of the Japanese Circulation Society 66 1065-1065 2002年10月20日  
  • 梅田 久視, 井澤 英夫, 山田 晶, 曽村 富士, 堀場 充, 武市 康志, 高田 康信, 磯部 智, 近藤 隆久, 因田 恭也, 赤星 誠, 野々川 信, 永田 浩, 平井 真理, 野田 明子, 岩瀬 三紀, 西澤 孝夫, 横田 充弘
    Circulation journal : official journal of the Japanese Circulation Society 66 1064-1064 2002年10月20日  
  • 井澤 英夫, 梅田 久視, 山田 晶, 曽村 富士, 堀場 充, 高田 康信, 武市 康志, 磯部 智, 近藤 隆久, 赤星 誠, 因田 恭也, 野々川 信, 永田 浩三, 平井 真理, 西澤 孝夫, 横田 充弘, 野田 明子, 岩瀬 三紀
    Circulation journal : official journal of the Japanese Circulation Society 66 1064-1064 2002年10月20日  
  • 武市 康志, 井澤 英夫, 梅田 久視, 山田 晶, 曽村 富士, 堀場 充, 高田 康信, 磯部 智, 近藤 隆久, 因田 恭也, 赤星 誠, 野々川 信, 永田 浩三, 平井 真理, 野田 明子, 岩瀬 三紀, 西澤 孝夫, 横田 充弘
    Circulation journal : official journal of the Japanese Circulation Society 66 1064-1064 2002年10月20日  
  • K Nagata, F Somura, K Obata, M Odashima, H Izawa, S Ichihara, T Nagasaka, M Iwase, Y Yamada, N Nakashima, M Yokota
    HYPERTENSION 40(2) 168-174 2002年8月  
    The possible role of calcineurin in the attenuation of cardiac hypertrophy and fibrosis by blockade of the angiotensin II type I (AT,) receptor was investigated in Dahl salt-sensitive (DS) rats. The effect of the calcineurin inhibitor FK506 was also studied. DS rats progressively developed severe hypertension when fed a diet containing 8% NaCl from 7 weeks of age. In addition, marked cardiac hypertrophy and fibrosis were apparent and the activity of calcineurin and its mRNA expression in the myocardium was increased in these animals at 12 weeks in comparison with age-matched Dahl salt-resistant rats. The abundance of angiotensin-converting enzyme (ACE) and transforming growth factor (TGF)-beta1 mRNAs was also increased in the hearts of DS rats at 12 weeks. Treatment of DS rats with a non-antihypertensive dose of the selective AT, receptor blocker candesartan (1 mg/kg per day) or FK506 (0.1 mg/kg per day) from 7 to 12 weeks attenuated both calcineurin activity and its mRNA expression in the heart, as well as the development of cardiac hypertrophy and fibrosis, without affecting cardiac function. Treatment with candesartan, but not FK506, prevented the upregulation of ACE and TGF-beta1 gene expression. Both candesartan and FK506 prevented the load-induced induction of fetal-type cardiac genes. These results demonstrate that AT, receptor blockade attenuates the development of cardiac hypertrophy and fibrosis as well as the activation of calcineurin, without an antihypertensive effect, in rats with salt-sensitive hypertension. Calcineurin may be downstream from TGF-beta1 in AT, receptor-mediated angiotensin II signaling in vivo.
  • 田中 俊郎, 飯野 重夫, 竹下 享典, 近藤 隆久, 平井 真理, 赤星 誠, 因田 恭也, 野々川 信, 井澤 英夫, 磯部 智, 高田 康信
    Journal of Cardiology 40(Suppl.1) 343-343 2002年8月  
  • 磯部 智, 岡田 充弘, 安藤 晃禎, 七里 守, 野々川 信, 高田 康夫, 高田 康信, 飯野 重夫, 赤星 誠, 因田 恭也, 井澤 英夫, 近藤 隆久, 平井 真理, 横田 充弘, 室原 豊明
    心電図 22(5) 443-443 2002年8月  
  • S Isobe, M Okada, A Ando, M Nanasato, M Nonokawa, H Izawa, T Kondo, M Hirai, M Yokota, Y Tanahashi, H Saito
    JOURNAL OF ELECTROCARDIOLOGY 35(3) 173-180 2002年7月  
    This article aims to clarify the clinical significance of changes in electrocardiographic (ECG) R-wave voltage on chest leads from I to 4 weeks in patients with acute anterior myocardial infarction (MI) in combination with echocardiographic findings and dual scintigraphic findings. Seventy-one patients with acute anterior MI who under-went emergency revascularization were subjected to ECG and echocardiography, at both 1 and 4 weeks, and to thallium-201 (TI) and iodine-123-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) about I week after the onset of MI. The total sum of ECG R-wave voltage on each chest lead was calculated. The mean defect ratio on TI and that on BMIPP derived from circumferential profile curve analysis were calculated. The percentage defect-discordant ratio of both SPECT images [(%) discordance on TI/BMIPP] was obtained. The percentage increase ratio of ECG R-wave voltage on chest leads [(%) increase of R wave] and the increase of left ventricular ejection fraction (DeltaEF) from 1 to 4 weeks were obtained. There were significant correlations between the (%) increase of R wave and the DeltaEF as well as between the (%) increase of R wave and the (%) discordance on TI/BMIPP (r=.63, P&lt;.001; r=.74, P&lt;.001). The reversibility of ECG R-wave voltage was related to cardiac functional improvement in addition to the discordance on the 2 images. Monitoring of changes in ECG R-wave voltage on chest leads is useful to detect the presence of myocardial viability and to evaluate functional evolution in patients with acute anterior MI.
  • S Isobe, A Ando, Y Takeichi, M Nanasato, M Nonokawa, F Somura, H Izawa, M Hirai, M Yokota
    JOURNAL OF NUCLEAR MEDICINE 43(5) 176P-176P 2002年5月  
  • IS Kim, H Izawa, T Sobue, H Ishihara, F Somura, T Nishizawa, K Nagata, M Iwase, M Yokota
    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 39(8) 1264-1268 2002年4月  
    OBJECTIVES The purpose of this study, was to determine, by, analyzing the pressure-volume relationship,,in the prognostic value of parameters related to myocardial energetic for predicting mortality patients with dilated cardiomyopathy (DCM) in sinus rhythm. BACKGROUND The relationship between the myocardial energetics and the prognosis of patients with DCM in sinus rhythm remains unclear. METHODS We followed 114 ambulatory, patients with nonischemic DCM in sinus rhythm for a mean period of 5.8 +/- 3.9 years. Over 70% of our patient,, were in New York Heart Association functional class I and class II. pressure-volume data were obtained by the conductance method, and myocardial oxygen consumption per beat (Vo(2)) measurements were obtained. RESULTS The 3-, 5-, and 10-year cumulative survival rates were 88.61%, 80.0%, and 73.9%, respectively. Of the 114 patients, 47 were selected randomly to assess their myocardial energetics. By univariate analysis, the mechanical efficiency, (ME, external work/Vo(2)), left ventricular (LV) ejection fraction and the LV end-diastolic pressure were statistically associated with cardiac death. The ME was the strongest predictor of survival in a Cox proportional-hazards, analysis (p = 0.011). The best cutoff point of ME identified by the receiver-operating Curve was 11%. This value had a sensitivity, of 100%, a specificity of 87% and an overall predictive accuracy of 88% to distinguish survivors from nonsurvivors. CONCLUSIONS This study clearly demonstrates that ME is a powerful clinical predictor for cardiac death in patients with mild to moderate heart failure and with sinus rhythm. Whether these conclusions apply, to patients with more severe heart failure requires further investigations. (C) 2002 by, the American College of Cardiology, Foundation.