Curriculum Vitaes

hayashi mutsuharu

  (林 睦晴)

Profile Information

Affiliation
Fujita Health University
Degree
博士(医学)

Other name(s) (e.g. nickname)
Mutsuharu Hayashi
J-GLOBAL ID
201501011689920266
researchmap Member ID
7000012724

Research Areas

 1

Papers

 51
  • Yuji Kono, Hideo Izawa, Yoichiro Aoyagi, Ryo Yamada, Tomoya Ishiguro, Masataka Yoshinaga, Satoshi Okumura, Wakaya Fujiwara, Mutsuharu Hayashi, Yohei Otaka
    Heart and vessels, 36(12) 1856-1860, Dec, 2021  
    The study aimed to identify factors related to bone mineral density (BMD) among older patients with heart failure (HF). A total of 70 consecutive patients with HF aged 65 years or older who were admitted to an acute hospital due to worsening condition were enrolled before discharge. BMD of the femoral neck was evaluated using the DEXA method. Physical function, as well as echocardiographic and laboratory findings including biomarker of HF severity were collected. Bivariate and multiple regression analyses were employed to determine the association between BMD and the clinical variables. Bivariate analysis determined that age, grip strength, walking speed, serum albumin, and N-terminal pro B-type natriuretic peptide (NT-proBNP) were significantly correlated with BMD (P < 0.01), whereas other clinical parameters were not. The multiple regression analysis identified NT-proBNP as an independent related factor for BMD after adjusting with confounding clinical variables. NT-proBNP was independently related to BMD among older patients with HF. Our results suggest the inclusion of bone fracture prevention strategies in disease management programs, especially for older patients with HF.
  • Hiroyuki Naruse, Junnichi Ishii, Hiroshi Takahashi, Fumihiko Kitagawa, Eirin Sakaguchi, Hideto Nishimura, Hideki Kawai, Takashi Muramatsu, Masahide Harada, Akira Yamada, Wakaya Fujiwara, Mutsuharu Hayashi, Sadako Motoyama, Masayoshi Sarai, Eiichi Watanabe, Hiroyasu Ito, Yukio Ozaki, Hideo Izawa
    Journal of Clinical Medicine, 10(16) 3564-3564, Aug 13, 2021  
    The prognostic role of D-dimer in different types of heart failure (HF) is poorly understood. We investigated the prognostic value of D-dimer on admission, both independently and in combination with the Get With The Guidelines—Heart Failure (GWTG-HF) risk score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients with preserved left ventricular ejection fraction (LVEF) and acute decompensated HF (HFpEF) or reduced LVEF (HFrEF). Baseline D-dimer levels were measured on admission in 1670 patients (mean age: 75 years) who were hospitalized for worsening HF. Of those patients, 586 (35%) were categorized as HFpEF (LVEF ≥ 50%) and 1084 as HFrEF (LVEF &lt; 50%). During the 12-month follow-up period after admission, 360 patients died. Elevated levels (at least the highest tertile value) of D-dimer, GWTG-HF risk score, and NT-proBNP were all independently associated with mortality in all HFpEF and HFrEF patients (all p &lt; 0.05). Adding D-dimer to a baseline model with a GWTG-HF risk score and NT-proBNP improved the net reclassification and integrated discrimination improvement for mortality greater than the baseline model alone in all populations (all p &lt; 0.001). The number of elevations in D-dimer, GWTG-HF risk score, and NT-proBNP were independently associated with a higher risk of mortality in all study populations (HFpEF and HFrEF patients; all p &lt; 0.001). The combination of D-dimer, which is independently predictive of mortality, with the GWTG-HF risk score and NT-proBNP could improve early prediction of 12-month mortality in patients with acute decompensated HF, regardless of the HF phenotype.
  • Tomoya Ishiguro, Mutsuharu Hayashi, Wakaya Fujiwara, Satoshi Okumura, Masataka Yoshinaga, Ryo Yamada, Sayano Ueda, Takehiro Ito, Yudai Niwa, Akane Miyazaki, Masahide Harada, Hiroyuki Naruse, Junnichi Ishii, Yukio Ozaki, Hideo Izawa
    Fujita medical journal, 7(1) 18-22, 2021  
    OBJECTIVES: MicroRNAs (miRNA) are functional RNAs that have emerged as pivotal gene expression regulators in cardiac disease. Although several cardiomyocyte miRNAs have been reported to play roles in heart failure progression among patients with idiopathic dilated cardiomyopathy (DCM), the role of circulating miRNAs has not yet been well-examined. METHODS: After total RNA extraction from the peripheral blood samples of three control participants and six patients with DCM, miRNA profiling was performed using miRNA arrays. Based on the results of this initial screening, real-time polymerase chain reaction (RT-PCR) was used to perform a quantitative analysis of blood samples from a larger number of matched patients (DCM, n=20; controls, n=5). Finally, the correlations between specific miRNA expression levels and hemodynamic parameters were analyzed. RESULTS: A primary screening of 2,565 miRNAs resulted in the identification of nine miRNA candidates. Quantitative RT-PCR results revealed significantly increased miR-489 expression levels in the DCM group. Moreover, there was a significant positive correlation between miR-489 expression level and left ventricular ejection fraction. CONCLUSIONS: Our results suggest that circulating miR-489 could be a potential noninvasive diagnostic biomarker for DCM. Additionally, the quantification of circulating miR-489 may have value as a potential prognostic marker for patients with DCM.
  • Ryo Yamada, Satoshi Okumura, Yuji Kono, Akane Miyazaki, Yudai Niwa, Takehiro Ito, Sayano Ueda, Tomoya Ishiguro, Masataka Yoshinaga, Wakaya Fujiwara, Mutsuharu Hayashi, Yukio Ozaki, Eiichi Saitoh, Hideo Izawa
    Fujita medical journal, 7(3) 76-82, 2021  
    OBJECTIVES: There are benefits of exercise-based cardiac rehabilitation (CR) in patients with heart failure (HF), but their underlying molecular mechanisms remain elusive. The effect of CR on the expression profile of circulating microRNAs (miRNAs), which are short noncoding RNAs that regulate posttranscriptional expression of target genes, is unknown. If miRNAs respond to changes following CR for HF, then serum profiling of miRNAs may reveal cardioprotective mechanisms of CR. METHODS: This study enrolled three hospitalized patients with progressed systolic HF and three normal volunteer controls. In patients, CR was initiated after improvement of HF, which included 2 weeks of bicycle ergometer and resistance exercises. Genome-wide expression profiling of circulating miRNAs was performed using microarrays for the patients (mean±SD age, 60.0±12.2 years) and controls (58.7±0.58 years). Circulating miRNA expression profiles were compared between patients with HF before and after CR and the controls. RESULTS: Expression levels of two miRNAs were significantly different in patients before CR compared with controls and patients after CR. The expression of hsa-miR-125b-1-3p was significantly downregulated and that of hsa-miR-1290 was significantly upregulated in patients before CR. CONCLUSIONS: When performing CR, expression of certain circulating miRNAs in patients with HF is restored to nonpathological levels. The benefits of CR for HF may result from regulation of miRNAs through multiple effects of gene expression.
  • Sayano Ueda, Yuji Kono, Ryo Yamada, Tomoya Ishiguro, Masataka Yoshinaga, Satoshi Okumura, Wakaya Fujiwara, Mutsuharu Hayashi, Yoichiro Aoyagi, Eiichi Saitoh, Yohei Otaka, Hideo Izawa
    Fujita medical journal, 7(2) 65-69, 2021  
    Background: Anaerobic threshold (AT) during cardiopulmonary exercise testing (CPET) is not always determinable in patients with heart failure (HF). However, little is known about the clinical features of patients with HF who have indeterminable AT. Therefore, the present study aimed to clarify the clinical features of such patients. Methods: A total of 70 patients with HF (58 males; age: 68±12 years) who underwent CPET during hospitalization were divided into two groups: determinable AT (n=50) and indeterminable AT (n=20). Physical function, echocardiographic results, and laboratory findings were subsequently determined. Results: Univariate analyses showed that the indeterminable AT group had significantly higher age and left ventricular ejection fraction, and significantly lower body mass index, calf circumference, handgrip strength, walking speed, serum hemoglobin, and serum albumin than the determinable AT group. Multiple logistic regression analysis identified handgrip strength and walking speed as independent predictive factors for indeterminable AT. Receiver-operating characteristic analyses revealed that handgrip strength of 21.2 kg and walking speed of 0.97 m/s were optimal cutoff values for differentiating patients who were likely to experience indeterminable AT. Conclusions: The present study identified handgrip strength and walking speed as powerful predictors for indeterminable AT with HF.

Misc.

 81
  • 西村 豪人, 石井 潤一, 河合 秀樹, 村松 崇, 原田 将英, 元山 貞子, 成瀬 寛之, 渡邉 英一, 林 睦晴, 井澤 英夫, 尾崎 行男
    日本循環器学会学術集会抄録集, 83回 OJ03-2, Mar, 2019  
  • 成瀬 寛之, 石井 潤一, 西村 豪人, 大田 将也, 河合 秀樹, 村松 崇, 原田 将英, 山田 晶, 元山 貞子, 林 睦晴, 皿井 正義, 井澤 英夫, 渡邉 英一, 尾崎 行男
    日本循環器学会学術集会抄録集, 83回 OJ03-3, Mar, 2019  
  • 西村 豪人, 石井 潤一, 河合 秀樹, 村松 崇, 原田 将英, 成瀬 寛之, 元山 貞子, 渡邉 英一, 林 睦晴, 井澤 英夫, 尾崎 行男
    日本循環器学会学術集会抄録集, 83回 OJ15-4, Mar, 2019  
  • 河野 裕治, 井澤 英夫, 青柳 陽一郎, 山田 亮, 石黒 智也, 良永 真隆, 奥村 聡, 藤原 稚也, 林 睦晴, 才藤 栄一
    日本循環器学会学術集会抄録集, 83回 CP03-1, Mar, 2019  
  • 河野裕治, 井澤英夫, 青柳陽一郎, 山田亮, 石黒智也, 良永真隆, 奥村聡, 藤原稚也, 林睦晴, 才藤栄一
    日本心不全学会学術集会プログラム・抄録集, 23rd, 2019  
  • 宮崎茜, 良永真隆, 林睦晴, 藤原稚也, 奥村聡, 山田亮, 石黒智也, 上田清乃, 多賀谷真央, 丹羽雄大, 井澤英夫
    日本心臓病学会学術集会(Web), 67th, 2019  
  • 山田亮, 奥村聡, 丹羽雄大, 宮崎茜, 伊藤丈浩, 上田清乃, 石黒智也, 良永真隆, 藤原稚也, 林睦晴, 成瀬寛之, 石井潤一, 尾崎行男, 井澤英夫
    日本心臓病学会学術集会(Web), 67th, 2019  
  • Wakaya Fujiwara, Yasuchika Kato, Mutsuharu Hayashi, Yoshinori Sugishita, Satoshi Okumura, Masataka Yoshinaga, Tomoya Ishiguro, Ryo Yamada, Sayano Ueda, Masahide Harada, Hiroyuki Naruse, Junnichi Ishii, Yukio Ozaki, Hideo Izawa
    Journal of Cardiology, 72 452-457, Dec 1, 2018  
    © 2018 Japanese College of Cardiology Background: Although cardiac sarcoidosis is associated with poor prognosis, diagnosis of the disease is challenging and the sensitivity and specificity of diagnostic modalities are limited. This study was performed to evaluate the potential of serum microRNAs (miRNAs) as diagnostic biomarkers for cardiac sarcoidosis. Methods: We performed genome-wide expression profiling for 2565 miRNAs (Human-miRNA ver.21) using peripheral blood samples from 5 patients with cardiac sarcoidosis (61 ± 9 years) and 3 healthy controls (54 ± 7 years). From this screening study, we selected 12 miRNAs that were significantly related to cardiac sarcoidosis. Next, we performed real-time polymerase chain reaction (PCR) on blood samples from 15 new patients with cardiac sarcoidosis and 4 healthy controls to quantify the expression of these 12 miRNAs. Results: In the screening study, 12 miRNAs were differentially expressed (p &lt; 0.01) in all 5 patients with cardiac sarcoidosis, showing greater fold-change values (&gt;4 or &lt;0.25) compared with the expression in the 3 healthy controls. Analysis of the real-time PCR for blood samples from the other 15 patients and 4 controls using Mann–Whitney U tests revealed that the expression of miR-126 and miR-223 was significantly higher in the patients than in the healthy individuals. However, there were no differences in the expressions of miRNA-126 and miR-223 between patients with only cardiac lesions and those with extra-cardiac lesions. Conclusions: Our results demonstrate the potential of serum miR-126 and miR-223 as new-generation biomarkers for the differential diagnosis of cardiac sarcoidosis in patients with heart failure.
  • 森 悦子, 河野 裕治, 石川 綾子, 杉浦 翼, 田中 康友, 青柳 陽一郎, 上田 清乃, 山田 亮, 石黒 智也, 藤原 稚也, 林 睦晴, 井澤 英夫
    心臓リハビリテーション, 24(3-4) 232-235, Nov, 2018  
    【目的】本研究の目的は、高齢心不全患者を対象に抑うつと身体機能との関連を検討した。【方法】65歳以上の心不全患者120例を対象とした。対象者をGeriatric Depression Scale(GDS-5)で抑うつなし群(GDS-5≦1)、抑うつあり群(GDS-5≧2)の2群に分け、心不全病態指標、身体機能、認知機能の項目についてχ2検定、対応のないt-検定を用いて比較した。【結果】全対象者のうち抑うつは58例(48%)に認めた。両群間の比較では年齢、性別、BMI、認知機能、病態指標には差を認めなかった。しかし身体機能(握力、等尺性膝伸展筋力、6分間歩行距離、歩行速度)は、抑うつ群で有意に低値を示した。【結論】本結果より高齢心不全患者の抑うつ合併例は身体機能が低下していることが明らかとなった。高齢心不全患者に対する身体的フレイル判定の際には、抑うつも評価する必要性が示唆された。(著者抄録)
  • Hiroyuki Naruse, Junnichi Ishii, Hiroshi Takahashi, Fumihiko Kitagawa, Hideto Nishimura, Hideki Kawai, Takashi Muramatsu, Masahide Harada, Akira Yamada, Sadako Motoyama, Shigeru Matsui, Mutsuharu Hayashi, Masayoshi Sarai, Eiichi Watanabe, Hideo Izawa, Yukio Ozaki
    Critical Care, 22(1), Aug 18, 2018  
    © 2018 The Author(s). Background: The early prediction of acute kidney injury (AKI) can facilitate timely intervention and prevent complications. We aimed to understand the predictive value of urinary liver-type fatty-acid binding protein (L-FABP) levels on admission to medical (non-surgical) cardiac intensive care units (CICUs) for AKI, both independently and in combination with serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Methods: We prospectively investigated the predictive value of L-FABP and NT-proBNP for AKI in a large, heterogeneous cohort of patients treated in medical CICUs. Baseline urinary L-FABP and serum NT-proBNP were measured on admission. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes criteria. We studied 1273 patients (mean age, 68years), among whom 46% had acute coronary syndromes, 38% had acute decompensated heart failure, 5% had arrhythmia, 3% had pulmonary hypertension, 2% had acute aortic syndrome, 2% had infective endocarditis, and 1% had Takotsubo cardiomyopathy. Results: Urinary L-FABP levels correlated with serum NT-proBNP levels (r=0.17, p&lt;0.0001). AKI occurred in 224 patients (17.6%), including 48 patients with stage 2 or 3 disease. Patients who developed AKI had higher one-week and 6-month mortality than those who did not develop AKI (p=0.0002 and p=0.003, respectively). In the multivariate logistic analysis, both L-FABP (p&lt;0.0001) and NT-proBNP (p=0.006) were independently associated with the development of AKI. Adding L-FABP and NT-proBNP to a baseline model that included established risk factors further improved reclassification (p&lt;0.001) and discrimination (p&lt;0.01) beyond that of the baseline model or any single biomarker individually. Conclusions: Urinary L-FABP and serum NT-proBNP levels on admission are independent predictors of AKI, and when used in combination, improve early prediction of AKI in patients hospitalized at medical CICUs.
  • 井澤英夫, 河野裕治, 青柳陽一郎, 上田清乃, 山田亮, 石黒智也, 良永真隆, 奥村聡, 藤原稚也, 林睦晴
    日本心不全学会学術集会プログラム・抄録集, 22nd, 2018  
  • Hiroyuki Naruse, Junnichi Ishii, Hiroshi Takahashi, Fumihiko Kitagawa, Ryuunosuke Okuyama, Hideki Kawai, Takashi Muramatsu, Masahide Harada, Akira Yamada, Sadako Motoyama, Shigeru Matsui, Mutsuharu Hayashi, Masayoshi Sarai, Eiichi Watanabe, Hideo Izawa, Yukio Ozaki
    CIRCULATION JOURNAL, 81(10) 1506-1513, Oct, 2017  
    Background: A modestly elevated circulating D-dimer level may be relevant to coronary artery disease (CAD), but its prognostic value, both independently and in combination with estimated glomerular filtration rate (eGFR), for long-term death has not been fully evaluated in stable CAD patients. Methods and Results: Baseline plasma D-dimer levels and eGFR were measured in 1,341 outpatients (mean age: 65 years) with prior myocardial infarction (MI), coronary revascularization, and/or angiographic evidence of a significant stenosis (&gt; 50%) for at least one of the major coronary arteries. Among these patients, 43% had prior MI, 47% had prior coronary revascularization, 41% had multivessel CAD, 14% had paroxysmal or persistent atrial fibrillation, 32% had diabetes, and 32% had chronic kidney disease (eGFR &lt; 60 mL/min/1.73 m2). D-dimer levels weakly correlated with eGFR (r=-0.25; P&lt; 0.0001). During a mean follow-up period of 73 months, there were 124 deaths, including 61 cardiovascular deaths. Multivariate Cox regression analysis identified D-dimer levels (P=0.001) and eGFR (P=0.006) as independent predictors of all-cause death. Adding both D-dimer and eGFR to a baseline model with established risk factors improved the net reclassification (P&lt; 0.005) and integrated discrimination improvement (P&lt; 0.05) greater than that of any single biomarker or baseline model alone. Conclusions: The combinatorial value of assessing D-dimer levels and eGFR may provide useful insight regarding stable CAD patients' long-term risk stratification.
  • Fumihiko Kitagawa, Junnichi Ishii, Shinya Hiramitsu, Hiroshi Takahashi, Ryuunosuke Okuyama, Hideki Kawai, Takashi Muramatsu, Masahide Harada, Sadako Motoyama, Hiroyuki Naruse, Shigeru Matsui, Masayoshi Sarai, Mutsuharu Hayashi, Eiichi Watanabe, Hideo Izawa, Yukio Ozaki
    HEART AND VESSELS, 32(5) 609-617, May, 2017  
    Whether trough-phase rivaroxaban concentrations provide sufficient anticoagulation needs more study. We evaluated levels of coagulation activation markers in the trough concentration phase in nonvalvular atrial fibrillation (NVAF) patients, and the correlation between these markers and rivaroxaban concentration. Fifty-five Japanese NVAF patients received 24-week rivaroxaban treatment of either 15 or 10 mg once-daily in the morning. Of these, 26 patients had no history of anticoagulant therapy (naive group) and 29 had switched from warfarin (warfarin group). D-dimer and prothrombin fragment 1 + 2 (F1 + 2) levels, and protein C activities were measured at 0 (baseline), 12 and 24 weeks of rivaroxaban treatment just before the patient's regular dosing time (trough phase). For 49 patients, D-dimer, F1 + 2, and rivaroxaban concentrations were also measured twice between 28 and 32 weeks of rivaroxaban treatment at non-trough times to achieve a range of drug concentrations for correlation analysis. For the naive group, D-dimer and F1 + 2 levels were significantly reduced (p &lt; 0.01) from baseline at 12 and 24 weeks. For the warfarin group, these values were unchanged for D-dimer but significantly increased (p &lt; 0.01) for F1 + 2. Protein C activity was unchanged in the naive group and was increased (p &lt; 0.01) in the warfarin group. Prothrombin time (r = 0.92, p &lt; 0.0001) and activated partial thromboplastin time (r = 0.54, p &lt; 0.0001) correlated with rivaroxaban concentration, but not D-dimer and F1 + 2 levels. In conclusion, rivaroxaban in the trough phase is comparable to warfarin in reducing D-dimer levels. Although trough level rivaroxaban suppresses F1 + 2 less than warfarin, the higher activities of protein C with rivaroxaban treatment compared to warfarin treatment may counterbalance this. Lack of correlation between rivaroxaban concentration and D-dimer and F1 + 2 levels suggests that trough concentrations of rivaroxaban reduce their concentrations as effectively as higher levels do.
  • Mutsuharu Hayashi, Yoshinari Yasuda, Susumu Suzuki, Manaka Tagaya, Takehiro Ito, Tomohito Kamada, Masataka Yoshinaga, Yoshinori Sugishita, Wakaya Fujiwara, Hiroatsu Yokoi, Yukio Ozaki, Hideo Izawa
    HEART AND VESSELS, 32(3) 279-286, Mar, 2017  
    Although the renin-angiotensin system (RAS) is counter-balanced by a salt-sensitive mechanism in the hypertensive state, both are reported to be up-regulated in chronic kidney disease (CKD) patients. We conducted this study to evaluate the associations among the RAS, renal function, hypertension, and atherosclerosis, as well as to identify markers for salt-sensitivity. A total of 213 pre-dialysis CKD patients with preserved cardiac function (EF &gt; 50 %) were enrolled. Their renal and cardiac biochemical markers and plasma renin activity (PRA) were measured, and echocardiography and carotid artery ultrasound were performed. Their salt intake was estimated by the NaCl excretion from a 24-h collected urine sample. The PRA was higher in patients with hypertension (p = 0.018), and had a significant negative correlation with the eGFR (r = -0.23, p = 0.0067). Importantly, the PRA had a strong negative correlation with the brain natriuretic peptide (BNP) level (r = -0.28, p = 0.017) regardless of whether the patients were being treated with RAS inhibitors. The BNP level was related to the renal functions (eGFR: p = 0.001, ACR: p = 0.009). There was a significant positive correlation between the BNP level and carotid intima-media thickness (p &lt; 0.001). A multivariate analysis revealed that older age and an excess of NaCl excretion were independent predictors of BNP elevation (p = 0.02 and 0.003, respectively). Our analysis revealed details of the counterbalance between BNP and PRA, as well as identifying that excess salt intake is a predictor of BNP elevation. These results indicate that the BNP could be a possible valuable marker for salt sensitivity, and that high salt sensitivity could facilitate atherosclerosis in CKD patients.
  • 河野裕治, 上田清乃, 山田亮, 石黒智也, 良永真隆, 杉下義倫, 奥村聡, 藤原稚也, 林睦晴, 井澤英夫
    日本心不全学会学術集会プログラム・抄録集, 21st, 2017  
  • Hideo Izawa, Yuji Kohno, Wakaya Fujiwara, Mutsuharu Hayashi
    CIRCULATION JOURNAL, 81(1) 28-29, Jan, 2017  
  • 井澤英夫, 河野裕治, 粥川知子, 青柳陽一郎, 才藤栄一, 藤原稚也, 林睦晴
    現代医学, 65(2) 71-75, 2017  Invited
  • Tomohito Kamada, Mutsuharu Hayashi, Wakaya Fujiwara, Daiji Yoshikawa, Daisuke Mukaide, Yoshinori Sugishita, Masataka Yoshinaga, Takehiro Itoh, Hiroatsu Yokoi, Junichi Ishii, Eiichi Watanabe, Yukio Ozaki, Hideo Izawa
    DRUG AND CHEMICAL TOXICOLOGY, 40(1) 110-114, Jan, 2017  
    Objectives: The number of elderly patients with hypertension has been steadily increasing. However, there are limited data on the safety and efficacy of the new angiotensin type 1 receptor blocker (ARB) azilsartan in elderly patients with hypertension. We investigated the clinical efficacy and safety of azilsartan in this population. Methods: The study population comprised 56 ambulatory patients with essential hypertension. We evaluated the reduction in blood pressure and safety after 12 weeks of treatment with azilsartan in 29 hypertensive patients65 years of age (aged group) in comparison with the findings in 27 patients &lt;65 years of age (non-aged group). Results: Systolic blood pressure in the aged group declined significantly from 155 +/- 18mmHg at baseline to 138 +/- 11mmHg after 12 weeks of treatment with azilsartan, and that in the non-aged group also declined significantly from 152 +/- 20mmHg at baseline to 142 +/- 13mmHg after 12 weeks of treatment with azilsartan. There were no significant differences in the magnitude of change in blood pressures from pre-treatment to post-treatment with azilsartan between the non-aged and aged groups. There were no changes in clinical laboratory findings, including serum levels of creatinine, potassium, lipids, and other metabolic variables, after 12 weeks of treatment with azilsartan in both groups. Conclusions: Our findings suggest that azilsartan is effective in lowering blood pressure in elderly patients and may be safe. Therefore, azilsartan could be a valuable option for treating hypertension in elderly and non-elderly patients.
  • Manaka Tagaya, Daiji Yoshikawa, Yoshinori Sugishita, Fumi Yamauchi, Takehiro Ito, Tomohito Kamada, Masataka Yoshinaga, Daisuke Mukaide, Wakaya Fujiwara, Hiroatsu Yokoi, Mutsuharu Hayashi, Eiichi Watanabe, Junichi Ishii, Yukio Ozaki, Hideo Izawa
    Heart and Vessels, 31 957-962, Jun 1, 2016  
    © 2015, Springer Japan. New oral anticoagulants (NOACs) are now clinically available. However, few studies have demonstrated which patients with non-valvular atrial fibrillation (NVAF) actually receive NOACs in a clinical setting. We analyzed 182 NVAF patients who received oral anticoagulants. Clinical backgrounds and the risk of stroke, systemic embolism, and bleeding associated with oral anticoagulants were investigated. Seventy-three (40 %) patients were treated with NOACs and 109 (60 %) patients were treated with warfarin. A significantly lower mean number of bleeding risk factors was observed among the patients treated with NOACs than among those treated with warfarin (P = 0.010). Of the bleeding risk factors, NOACs were significantly less frequently prescribed in patients with a bleeding history and elderly subjects (&gt;65 years) than in those who received warfarin (P &lt; 0.001 and P = 0.029). A multivariate logistic regression analysis revealed that CHF and bleeding history were independently and significantly associated with the administration of NOACs (P = 0.047 and P = 0.003). The rate of a history of intracranial hemorrhage was comparable between the patients treated with NOACs and those treated with warfarin (P = 1.000). Significantly lower rates of a history of gastrointestinal and other minor bleeding were observed in the patients who received NOACs versus those who received warfarin (P = 0.001 and P = 0.026). NOACs were less frequently prescribed in patients with a history of bleeding, especially those with a history of gastrointestinal bleeding in a clinical setting.
  • Sawai A, Yasuda Y, Suzuki S, Ishii H, Goto M, Kato S, Hayashi M, Maruyama S, Murohara T, Oiso Y, Matsuo S
    Clinical and experimental nephrology, 20(3) 416-24, Jun, 2016  Peer-reviewed
  • Mutsuharu Hayashi, Tomohito Kamada, Hiroatsu Yokoi, Wakaya Fujiwara, Daiji Yoshikawa, Daisuke Mukaide, Yoshinori Sugishita, Masataka Yoshinaga, Takehiro Ito, Yukio Ozaki, Hideo Izawa
    Internal Medicine, 55(3) 323-323, Feb 1, 2016  
  • Tatami Y, Yasuda Y, Suzuki S, Ishii H, Sawai A, Shibata Y, Ota T, Shibata K, Niwa M, Morimoto R, Hayashi M, Kato S, Maruyama S, Murohara T
    Atherosclerosis, 243(2) 349-55, Dec, 2015  Peer-reviewed
  • 良永真隆, 林睦晴, 横井博厚, 藤原稚也, 吉川大治, 向出大介, 杉下義倫, 鎌田智仁, 伊藤丈浩, 多賀谷真央, 井澤英夫
    心臓, 47(10), 2015  
  • 伊藤丈浩, 林睦晴, 横井博厚, 藤原稚也, 杉下義倫, 良永真隆, 鎌田智仁, 多賀谷真央, 井澤英夫
    日本循環器学会東海地方会(Web), 146th, 2015  
  • 良永真隆, 林睦晴, 横井博厚, 藤原稚也, 吉川大治, 杉下義倫, 鎌田智仁, 伊藤丈浩, 多賀谷真央, 井澤英夫
    日本循環器学会東海地方会(Web), 146th, 2015  
  • Shibata Y, Sone T, Tsuboi H, Isobe S, Ishii H, Suzuki S, Hayashi M, Murohara T
    Nagoya J Med Sci., 77(1) 155-166-166, 2015  Peer-reviewed
  • Kumagai S, Amano T, Takashima H, Waseda K, Kurita A, Ando H, Maeda K, Ito Y, Ishii H, Hayashi M, Yoshikawa D, Suzuki S, Tanaka A, Matsubara T, Murohara T
    Coronary Artery Disease, 26 60-65, 2015  Peer-reviewed
  • Tomohito Kamada, Mutsuharu Hayashi, Hiroatsu Yokoi, Wakaya Fujiwara, Daiji Yoshikawa, Daisuke Mukaide, Yoshinori Sugishita, Masataka Yoshinaga, Takehiro Ito, Yukio Ozaki, Hideo Izawa
    Internal Medicine, 54 31-35, Jan 1, 2015  
    © 2015 The Japanese Society of Internal Medicine. Takotsubo cardiomyopathy is a disorder characterized by left ventricular apical ballooning with preceding emotional and/or physical stressors. This condition is also an important differential diagnosis of acute coronary syndrome. We herein describe a case of Takotsubo cardiomyopathy, a significant clinical phenomenon, triggered by delayed-onset rhabdomyolysis following the administration of long-term statin treatment, without any preceding stressors or changes in the patient’s medical condition, in association with complaints of nonspecific muscle-related symptoms. Although an electrocardiogram showed remarkable ST-segment elevation, a careful reading of the electrocardiogram findings revealed the features of Takotsubo cardiomyopathy. Withdrawing the statin therapy improved the patient’s cardiac function.
  • Masataka Yoshinaga, Daiji Yoshikawa, Hideki Ishii, Akihiro Hirashiki, Takahiro Okumura, Aki Kubota, Shinichi Sakai, Ken Harada, Fuji Somura, Tomofumi Mizuno, Wakaya Fujiwara, Hiroatsu Yokoi, Mutsuharu Hayashi, Junichi Ishii, Yukio Ozaki, Toyoaki Murohara, Yukihiko Yoshida, Tetsuya Amano, Hideo Izawa
    International Heart Journal, 56(4) 415-420, Jan 1, 2015  
    © 2015, International Heart Journal Association. All rights reserved. Hypertrophic cardiomyopathy (HCM) has various morphological and clinical features. A decade has passed since the previous survey of the epidemiological and clinical characteristics of Japanese HCM patients. The Aichi Hypertrophic Cardiomyopathy (AHC) Registry is based on a prospective multicenter observational study of HCM patients. The clinical characteristics of 42 ambulant HCM patients followed up for up to 5 years were investigated. The primary endpoint was major adverse cardiac events (MACE), defined as death, non-fatal stroke, admission due to congestive heart failure (CHF), or episodes of sustained ventricular tachycardia/fibrillation. The MACE-free survival during the 5-year follow-up period was 76% according to Kaplan–Meier analysis. HCM-related death occurred in 3 (7%) patients and SCD occurred in 2 (5%) patients. Additionally, 3 (7%) patients were admitted to the hospital due to CHF. Meanwhile, sustained VT was detected in one (2%) of the patients who received ICD implantation and subsequently terminated with antitachycardia pacing using an ICD. The patients with HCM exhibiting left ventricular outflow obstruction (HOCM) had a slightly lower MACE-free survival rate than those with neither HOCM nor dilated-HCM (dHCM) (71% versus 81%, log-rank P = 0.581). Furthermore, the patients with dHCM demonstrated a significantly lower MACE-free survival rate than those with neither HOCM nor dHCM (33% versus 81%, log-rank P = 0.029). In the AHC Registry targeting current Japanese HCM patients, we demonstrated that many HCM patients continue to suffer from MACE despite the development of various treatments for HCM.
  • Hongxian Wu, Xian Wu Cheng, Lina Hu, Chang-Ning Hao, Mutsuharu Hayashi, Kyosuke Takeshita, Mohammad Shoaib Hamrah, Guo-Ping Shi, Masafumi Kuzuya, Toyoaki Murohara
    CIRCULATION, 130, Nov, 2014  
  • 椿井 朋, 柴田 佳菜子, 濱田 昌実, 水谷 友, 安田 宜成, 加藤 佐和子, 後藤 資実, 林 睦晴, 中尾 誠
    日本医療薬学会年会講演要旨集, 24 370-370, Aug 25, 2014  
  • 伊藤丈浩, 林睦晴, 横井博厚, 藤原稚也, 吉川大治, 向出大介, 杉下義倫, 良永真隆, 鎌田智仁, 山田亮, 石黒智也, 井澤英夫
    日本循環器学会東海地方会(Web), 144th, 2014  
  • Satoshi Okumura, Masaki Sakakibara, Ryo Hayashida, Yasushi Jinno, Akihito Tanaka, Koji Okada, Mutsuharu Hayashi, Hideki Ishii, Toyoaki Murohara
    HEART AND VESSELS, 29(1) 7-14, Jan, 2014  Peer-reviewed
    High low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol (L/H) ratio is associated with progressions of coronary arteriosclerosis and chronic kidney disease. On the other hand, renal function markedly declined after acute myocardial infarction (AMI). The aims of the present study were (1) to identify what type of patients with AMI would have high L/H ratio at follow-up and (2) to evaluate whether decline in renal function after AMI had accelerated or not in patients with high L/H ratio. The 190 eligible AMI patients who underwent primary percutaneous coronary intervention (PCI) and received atorvastatin (10 mg) were divided into one of two groups according to the L/H ratio at 6-month follow-up: L/H &gt; 2 group (n = 81) or L/H a parts per thousand currency sign2 group (n = 109). The characteristics on admission in the two groups were examined. Furthermore, changes in serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) during 1- and 6-month follow-up were compared between the two groups. L/H &gt; 2 group were significantly younger and had greater body mass index (BMI) and worse lipid profile on admission compared with L/H a parts per thousand currency sign2 group. Percentage increase in sCr and percentage decrease in eGFR during 1-month follow-up in L/H &gt; 2 group tended to be greater than in L/H a parts per thousand currency sign2 group, and those during 6-month follow-up were significantly greater (16.5 +/- A 2.77 vs. 9.79 +/- A 2.23 %, p = 0.03 and 11.8 +/- A 1.93 vs. 2.75 +/- A 3.85 %, p = 0.04, respectively). In AMI patients undergoing primary PCI, those who were young and had large BMI and poor lipid profile on admission were likely to have a high L/H ratio at follow-up despite statin therapy. In addition, the decline in renal function after AMI had significantly accelerated in patients with high L/H ratio.
  • Masaya Matsumoto, Daiji Yoshikawa, Hideki Ishii, Yosuke Inoue, Susumu Suzuki, Miho Tanaka, Soichiro Kumagai, Satoshi Okumura, Mutsuharu Hayashi, Hirohiko Ando, Tetsuya Amano, Toyoaki Murohara
    International Journal of Cardiology, 167(2) 613-617, Jul 31, 2013  
  • Enyu Imai, Yoshinari Yasuda, Masaru Horio, Kanako Shibata, Sawako Kato, Yu Mizutani, Junko Imai, Mutsuharu Hayashi, Hideki Kamiya, Yutaka Oiso, Toyoaki Murohara, Shoichi Maruyama, Seiichi Matsuo
    CLINICAL AND EXPERIMENTAL NEPHROLOGY, 17(2) 316-316, Apr, 2013  
  • Bummei Sato, Daiji Yoshikawa, Hideki Ishii, Susumu Suzuki, Yosuke Inoue, Kyosuke Takeshita, Miho Tanaka, Soichiro Kumagai, Masaya Matsumoto, Satoshi Okumura, Mutsuharu Hayashi, Tatsuaki Matsubara, Toshimitsu Niwa, Toyoaki Murohara
    AMERICAN JOURNAL OF CARDIOLOGY, 111(5) 712-716, Mar, 2013  Peer-reviewed
    The prognosis of patients with diastolic heart failure (HF) is as poor as that of patients with systolic HF. Greater chronic kidney disease-associated mortality occurs in patients with left ventricular (LV) diastolic HF than in those with systolic HF. Indoxyl sulfate (IS), a uremic toxin, directly affects cardiac cells adversely in in vitro experiments. We investigated the association of IS, a uremic toxin, and chronic kidney disease with LV diastolic dysfunction in the clinical setting. The present study included 204 consecutive patients with preserved LV systolic function. To evaluate LV function, all patients underwent echocardiography. To measure the plasma IS levels and estimated glomerular filtration rate (eGFR), blood samples were obtained. Of the 204 patients, 75 (37%) had LV diastolic dysfunction. A significantly lower prevalence of LV diastolic dysfunction was present in patients with lower plasma IS levels (&lt;= 1.0 mu g/ml) than those with greater plasma IS levels (38 [29%] vs 37 [51%], p &lt;0.001). Furthermore, a significantly lower prevalence of LV diastolic dysfunction was present in patients with lower plasma IS levels and preserved eGFR than those with greater plasma IS levels and preserved eGFR, those with lower plasma IS levels and a reduced eGFR, or those with greater plasma IS levels and reduced eGFR (20 [21%] vs 18 [53%], p = 0.001; 20 [21%] vs 18 [46%], p = 0.004; and 20 [21%] vs 19 [56%], p &lt;0.001, respectively). In conclusion, greater plasma IS levels or a reduced eGFR, or both, represent an increased risk of LV diastolic dysfunction. (c) 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;111:712-716)
  • Hideki Ishii, Toru Aoyama, Hiroshi Takahashi, Daisuke Kamoi, Miho Tanaka, Daiji Yoshikawa, Mutsuharu Hayashi, Tatsuaki Matsubara, Toyoaki Murohara
    ATHEROSCLEROSIS, 227(1) 130-134, Mar, 2013  Peer-reviewed
    Objective: Peripheral artery disease (PAD) is frequently seen in hemodialysis patients, endovascular therapy (EVT) often being performed in such cases. We examined combined prognostic utility of pre-procedural serum albumin and C-reactive protein (CRP) in combination for predicting clinical outcome after EVT in HD patients with PAD. Methods: A total of 450 hemodialysis patients successfully undergoing EVT for PAD were followed-up for up to 8 years. They were divided according to median serum albumin and CRP levels measured prior to EVT into four groups [those with high albumin and low and high CRP levels, respectively, and low albumin and low and high CRP levels, respectively]. We analyzed the incidence of major adverse events (MAE) as a composite endpoint including target lesion revascularization (TLR), amputation and all-cause death, and major adverse limb events (MALE) as a composite endpoint including TLR and amputation. Results: During the follow-up period (36 +/- 31months), 206 MAE (46%) including 67 TLR, 45 amputations and 94 deaths occurred. Event-free survival rates from MAE for 8 years were 41.9%, 21.2%, 29.8%, and 13.2% in groups with high albumin and low CRP levels, with high albumin and high CRP levels, with low albumin and low CRP levels, and with low albumin and high CRP levels, respectively (P = 0.0001). Similar tendency was also seen in incidence of MALE (P &lt; 0.0001). Conclusion: Lower albumin and elevated CRP levels could strongly predict MAE and MALE after EVT in hemodialysis patients. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
  • Bummei Sato, Daiji Yoshikawa, Hideki Ishii, Ryosuke Kikuchi, Takeshi Arima, Kyosuke Takeshita, Yosuke Inoue, Susumu Suzuki, Miho Tanaka, Soichiro Kumagai, Masaya Matsumoto, Mutsuharu Hayashi, Hirohiko Ando, Tetsuya Amano, Tatsuaki Matsubara, Toshimitsu Niwa, Toyoaki Murohara
    International Journal of Cardiology, 163(2) 214-216, Feb 20, 2013  Peer-reviewed
  • Daiji Yoshikawa, Hideki Ishii, Nobutake Kurebayashi, Bummei Sato, Seiichi Hayakawa, Hirohiko Ando, Mutsuharu Hayashi, Satoshi Isobe, Takahiro Okumura, Akihiro Hirashiki, Kyosuke Takeshita, Tetsuya Amano, Tadayuki Uetani, Sumio Yamada, Toyoaki Murohara
    International Journal of Cardiology, 162(2) 123-128, Jan 10, 2013  Peer-reviewed
    Background: Cardiorespiratory fitness (CRF) can predict future cardiovascular disease. Rupture of vulnerable plaque which often has a large lipid core with a thin fibrous cap causes acute coronary syndrome including sudden cardiac death. We tested our hypothesis that preserved CRF is associated with low lipid composition and thick fibrous cap thickness of coronary lesions. Methods: We prospectively performed both integrated backscatter intravascular ultrasound (IB-IVUS) and optical coherence tomography (OCT) for 77 non-culprit coronary lesions in 77 consecutive angina pectoris patients who underwent percutaneous coronary intervention (PCI). Percentage of achieved of predicted peak oxygen consumption (%PPeak Vo2) calculated based on measured peak Vo2 using a cardiopulmonary exercise test performed post PCI was adapted as an indicator of patient CRF. Results: Patients were divided into two groups [those with preserved CRF (%PPeak Vo2 &gt 82%) (Group I) or others (Group II)]. Coronary plaques of Group I patients had significantly smaller lipid volume, greater fibrous volume, and thicker fibrous cap thickness than those of Group II (32 ± 14% vs. 45 ± 13%, p &lt 0.001 57 ± 11% vs. 49 ± 11%, p &lt 0.001 and 177.7 ± 20.9 μm vs. 143.7 ± 36.9 μm, p &lt 0.001). In multivariate linear regression analysis, %PPeak Vo2 showed a significantly negative correlation with lipid volume and a positive correlation with fibrous volume and fibrous cap thickness (β = - 0.418, p = 0.001 β = 0.361, p = 0.006 and β = 0.339, p = 0.008). Conclusions: High %PPeak Vo2 was associated with low lipid volume, high fibrous volume and thick fibrous cap thickness in coronary lesions. These results may well suggest an attenuated risk of cardiovascular events in patients with preserved CRF. © 2011 Elsevier Ireland Ltd.
  • Takuya Okada, Daiji Yoshikawa, Hideki Ishii, Masaya Matsumoto, Seiichi Hayakawa, Kyoko Matsudaira, Miho Tanaka, Soichiro Kumagai, Mutsuharu Hayashi, Hirohiko Ando, Tetsuya Amano, Toyoaki Murohara
    JOURNAL OF CARDIOLOGY, 61(1-2) 188-188, Jan, 2013  
  • Yosuke Inoue, Daiji Yoshikawa, Hideki Ishii, Satoshi Isobe, Soichiro Kumagai, Susumu Suzuki, Satoshi Okumura, Mutsuharu Hayashi, Tatsuaki Matsubara, Satoru Ohshima, Hiroshi Banno, Kimihiro Komori, Katsuhiko Kato, Toyoaki Murohara
    Circulation Journal, 77(5) 1229-1234, 2013  Peer-reviewed
    Background: After abdominal aortic aneurysm (AAA) repair, relatively low survival during long-term follow-up remains an unresolved issue. Stress myocardial perfusion single-photon emission computed tomography (SPECT) well predicts future mortality overall, as well as providing diagnoses of coronary artery disease. The prognostic value of myocardial SPECT findings after AAA repair, however, remains unclear. Methods and Results: This study followed 285 patients, all undergoing preoperative pharmacologic stress myocardial perfusion SPECT to determine summed stress score (SSS), then elective AAA repair by open AAA repair or endovascular aneurysm repair. The endpoint of the study was cardiac death. The median follow-up duration was 925 days (range, 541-1,095 days). Twenty-four (8%) died during follow-up. Kaplan-Meier analysis showed that patients with SSS ≥9 had a significantly poorer prognosis than those with SSS &lt 9 (76% vs. 93%, P=0.003). Multivariate Cox proportional hazards analysis indicated that SSS ≥9, diabetes, and chronic kidney disease ≥ stage 3 could significantly and independently predict long-term cardiovascular mortality in patients after AAA repair (hazard ratio [HR], 4.2 95% confidence interval [CI]: 1.8-9.7, P=0.001 HR, 3.0 95% CI: 1.2-7.4, P=0.020 and HR, 4.1 95% CI: 1.7-10.1, P=0.029, respectively). Conclusions: Preoperative pharmacologic stress myocardial perfusion SPECT is a useful method to predict longterm cardiovascular mortality for patients undergoing elective AAA repair.
  • Comparison of, tissue characteristic between left main, non-left main coronary artery lesions - Assessment using integrated backscatter intravascular ultrasound
    Int J Cardiol, Nov 15, 2012  Peer-reviewed
  • Takuya Okada, Daiji Yoshikawa, Hideki Ishii, Masaya Matsumoto, Seiichi Hayakawa, Kyoko Matsudaira, Miho Tanaka, Soichiro Kumagai, Mutsuharu Hayashi, Hirohiko Ando, Tetsuya Amano, Toyoaki Murohara
    JOURNAL OF CARDIOLOGY, 60(3-4) 264-269, Sep, 2012  Peer-reviewed
    Background and purpose: Percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) is one of the standard treatments for patients with stable angina pectoris (AP). In spite of a notable effect in preventing restenosis after PCI, DES cannot improve the mortality of patients compared to a bare-metal stent (BMS). On the other hand, periprocedural myocardial injury (PMI) is related to poor prognosis in patients undergoing PCI. We compared DES to BMS in the incidence of PMI in patients with stable AP. Methods and subjects: We enrolled 265 consecutive patients with AP undergoing successful stent implantation. A blood sample was obtained from all patients immediately before and 24 h after PCI. PMI was defined as an increase in creatine kinase-myocardial band isozyme fraction (CK-MB) greater than the upper limit of reference range 24 h after PCI. During the study period, sirolimus- and paclitaxel-eluting stents were used as DES. The strategy of PCI including the type of stent to implant was left to the discretion of the operator. Results: Patients were divided into two groups (DES group, n = 136 and BMS group, n = 129). The incidence of PMI was significantly higher in the DES group than in the BMS group (24% vs. 12%, p = 0.015). Use of DES remained an independent predictor of PMI on multivariate logistic regression analysis after adjustment for confounding factors (odds ratio 2.20, 95% CI, 1.07-4.51, p = 0.032). Conclusions: Implantation of the first-generation DES including sirolimus- and paclitaxel-eluting stents was associated with a higher incidence of PMI in patients with AP compared to BMS. (C) 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
  • Masaya Matsumoto, Daiji Yoshikawa, Hideki Ishii, Seiichi Hayakawa, Miho Tanaka, Soichiro Kumagai, Mutsuharu Hayashi, Toyoaki Murohara
    NAGOYA JOURNAL OF MEDICAL SCIENCE, 74(3-4) 253-259, Aug, 2012  Peer-reviewed
    Coronary calcification is proportional to the extent and severity of atherosclerotic disease, and is a predictor of cardiac events. Furthermore, coronary calcification protruding into the lumen is considered as one type of vulnerable plaque. Optical coherence tomography (OCT) can provide in vivo imaging of the detailed vessel wall structure of the coronary artery with high resolution, as in the histological approach. We analyzed coronary calcification in that fashion using OCT in vivo. This study consisted of 70 superficial coronary calcifications of 39 consecutive patients who underwent percutaneous coronary intervention. After revascularization, OCT was performed in the treated vessel. We analyzed morphologic characteristics and the quantification of OCT-determined coronary calcification. Superficial coronary calcifications were classified into two groups depending on whether they did not intrude the lumen (type I) or did (type II). The distance from the lumen and the volume of each calcification were then measured. Superficial coronary calcifications were classified into two groups; type I, n = 39 (56%) and type II, n = 31 (44%). Type II calcifications were located significantly closer to the lumen [80 mu m (60-130) vs. 130 mu m (90-260), p = 0.015], and tended to be smaller, but did not show a significant difference [0.65 (0.26-1.3) mm(3) vs. 1.2 (0.47-1.9) mm(3), p = 0.153] compared to those of type I. In conclusion, OCT could visualize superficial coronary calcifications in detail and enable us to evaluate in vivo morphologic characterizations and quantify them.
  • Hideki Ishii, Takanobu Toriyama, Toru Aoyama, Hiroshi Takahashi, Miho Tanaka, Daiji Yoshikawa, Mutsuharu Hayashi, Yoshinari Yasuda, Shoichi Maruyama, Seiichi Matsuo, Tatsuaki Matsubara, Toyoaki Murohara
    CIRCULATION JOURNAL, 76(7) 1609-1615, Jul, 2012  Peer-reviewed
    Background: Percutaneous coronary intervention (PCI) with drug-eluting stent (DES) is widely performed in patients with coronary artery disease, but the high restenosis rate remains a major clinical problem after implantation of DES in patients on hemodialysis (HD). Until now, there are limited reports regarding the long-term clinical outcome after implantation of DES in this patient population. Methods and Results: We compared bare metal stent (BMS) and DES for long-term clinical outcomes, such as target lesion revascularization (TLR), in HD patients undergoing PCI. BMS and DES were implanted in 204 and 301 patients, respectively. Baseline and lesion characteristics were comparable between the 2 groups. By Kaplan-Meier analysis, event rates of major adverse cardiac events for 6 years were significantly lower in the DES group than in the BMS group (42.5% vs. 58.0%, P=0.036). Although there were no significant differences in TLR rates between patients treated with DES and those with BMS at 1 year after PCI (17.8% vs. 21.3%, P=0.32), patients treated with DES had significantly lower rates of TLR compared with those treated with BMS beyond the 1-year follow-up after PCI (16.4% vs. 30.9%, P=0.019). Conclusions: In patients on HD, implantation of DES might be more effective for preventing TLR in the medium to long follow-up period than BMS, although restenosis after PCI with DES is common in the short term. (Circ J 2012; 76: 1609-1615)
  • H. Ishii, Y. Kumada, H. Takahashi, T. Toriyama, T. Aoyama, M. Tanaka, D. Yoshikawa, M. Hayashi, H. Kasuga, Y. Yasuda, S. Maruyama, T. Matsubara, S. Matsuo, T. Murohara
    DIABETOLOGIA, 55(5) 1304-1309, May, 2012  Peer-reviewed
    Aims/hypothesis End-stage renal disease (ESRD) patients with diabetes have been regarded as being at the highest risk of cardiovascular disease. We therefore investigated the relationship between diabetes and the incidence of peripheral artery disease (PAD) in new haemodialysis patients. Methods We enrolled 1,513 ESRD patients who had just begun haemodialysis therapy. They were divided into two groups: those with (n=739) and those without diabetes (n=774). The endpoint was the development of PAD, defined as ankle brachial pressure index &lt;= 0.9 or toe brachial pressure index &lt;0.7 in patients with an ankle brachial pressure index &gt;0.9. Results According to the Kaplan-Meier method, the 10 year event-free rate for development of PAD and lower limb amputation was significantly lower in the diabetes group than in the non-diabetes group (60.3% vs 82.8%, HR 2.99, 95% CI 2.27, 3.92, p&lt;0.0001 and 93.9% vs 98.9%, HR 5.59, 95% CI 2.14, 14.7, p=0.0005 for PAD and lower limb amputation, respectively). In patients with diabetes, quartile analysis of HbA(1c) levels showed that the highest quartile group (&gt;= 6.8% [51 mmol/mol]) had significant development of PAD and lower limb amputation compared with lower quartile groups (PAD HR 1.63, 95% CI 1.17, 2.28, p=0.0038; lower limb amputation HR 2.99, 95% CI 1.17, 7.70, p=0.023). Conclusions/interpretation Diabetes was a strong predictor of PAD after initiation of haemodialysis therapy in patients with ESRD. In addition, higher HbA1c levels were associated with increased risk of developing PAD and requiring limb amputation in such diabetic populations.
  • Soichiro Kumagai, Hideki Ishii, Tetsuya Amano, Tadaruki Uetani, Bunichi Kato, Ken Harada, Tomohiro Yoshida, Hirohiko Ando, Ayako Kunimura, Yusaku Shimbo, Katsuhide Kitagawa, Kazuhiro Harada, Mutsuharu Hayashi, Daiji Yoshikawa, Tatsuaki Matsubara, Toyoaki Murohara
    NEPHROLOGY DIALYSIS TRANSPLANTATION, 27(3) 1059-1063, Mar, 2012  Peer-reviewed
    Background. It is well known that chronic kidney disease is a strong independent predictor of adverse outcomes after percutaneous coronary intervention in patients with ischemic heart disease. Recently, pen-procedural myocardial injury has been associated with adverse cardiac events. The aim of this study was to investigate the relationship between renal function and pen-procedural myocardial injury in patients undergoing elective stent implantation. Methods. This study comprised 273 consecutive patients who underwent elective stent implantation. They were divided into two groups: estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1.73m(2) and eGFR &gt;= 60 mL/min/1.73m(2). Pen-procedural TnT levels higher than three times the normal limit were defined as pen-procedural myocardial injury. Results. Patients with eGFR &lt;60 mL/min/1.73m(2) showed a higher incidence of pen-procedural myocardial injury compared to patients with eGFR &gt;= 60 mL/min/1.73m(2) (4.3 versus 20.9%, P &lt; 0.0001). Even after a multivariate adjustment, the eGFR level predicted pen-procedural myocardial injury [odds ratio 0.92, 95% confidence interval (CI): 0.89-0.95, P &lt; 0.0001]. Total stent length was also an independent predictor of pen-procedural myocardial injury (odds ratio 1.09, 95% CI: 1.02-1.16, P = 0.009). Using a receiver-operating curve analysis, eGFR level of 62.1 mL/min/1.73m(2) (sensitivity 93.3%, specificity 57.2%) was the best value (area under the curve = 0.803) to maximize the power of eGFR levels in predicting pen-procedural myocardial injury. Conclusions. Patients with eGFR &lt;60 mL/min/1.73m(2) were strongly associated with pen-procedural myocardial injury after elective stent implantation. Therefore, eGFR may be a simple and convenient predictor of peri-procedural myocardial injury.
  • Takashi Sakakibara, Hideki Ishii, Takanobu Toriyama, Toru Aoyama, Hiroshi Takahashi, Daisuke Kamoi, Yoshihiro Kawamura, Kazuhiro Kawashima, Kohei Yoneda, Tetsuya Amano, Miho Tanaka, Daiji Yoshikawa, Mutsuharu Hayashi, Tatsuaki Matsubara, Toyoaki Murohara
    CIRCULATION JOURNAL, 76(2) 351-355, Feb, 2012  Peer-reviewed
    Background: Even in the drug-eluting stent era, adverse cardiac events, including restenosis after percutaneous coronary intervention (PCI), have been more frequently seen in patients on hemodialysis (HD) than in non-HD patients. The objective of this study was to compare the sirolimus-eluting stent (SES) and everolimus-eluting stent (EES) for prevention of adverse cardiac events, including restenosis, in HD patients. Methods and Results: A total of 100 consecutive patients on HD who underwent PCI were enrolled and randomly assigned to receive SES or EES. Although there was no difference between the 2 groups in baseline patient and lesion characteristics, the angiographic restenosis rate at 8-month follow-up was 21.2% in the SES group and 8.7% in the EES group (P=0.041). Significant differences were also seen in % diameter stenosis (%DS), minimal lumen diameter, and late lumen loss at 8-month follow-up (P=0.0024, P=0.0040, and P=0.033, respectively). During the 1-year follow-up, major adverse cardiac events occurred in 11(22.0%) patients in the SES group and in 5 (10.0%) patients in the EES group (P=0.10). Conclusions: The use of EES was as safe as that of SES. Moreover, EES significantly prevented restenosis in patients on maintenance HD compared with SES. (Circ J 2012; 76: 351-355)
  • Seiichi Hayakawa, Daiji Yoshikawa, Hideki Ishii, Miho Tanaka, Soichiro Kumagai, Masaya Matsumoto, Mutsuharu Hayashi, Tsuyoshi Sugiura, Kazunori Hayashi, Hirohiko Ando, Tetsuya Amano, Toyoaki Murohara
    INTERNAL MEDICINE, 51(9) 1009-1014, 2012  Peer-reviewed
    Objective Eicosapentaenoic acid (EPA) of the omega-3 polyunsaturated fatty acids (omega-3 PUFA) family plays important roles in the prevention of cardiovascular disease (CVD), while, arachidonic acid (AA) of the omega-6 PUFA family promotes inflammatory and prothrombotic influences. The complexity of coronary lesions represents the vulnerability of patients. The aim of this study was to investigate the association between the plasma EPA/AA ratio and the prevalence of complex coronary lesion morphology. Methods This study consisted of 206 consecutive patients with stable angina pectoris (sAP). Each coronary lesion was determined either as complex or simple based on angiographic findings. To examine the plasma fatty acid level, blood samples were obtained. Patients were divided into three groups according to the obtained plasma EPA/AA ratio: the highest tertile, n=67, the 2nd tertile, n=70, or the lowest tertile, n=69. Results A higher incidence of complex coronary lesion was obtained from patients with a lower plasma EPA/AA ratio [43 (62%) vs. 31 (44%) vs. 25 (37%), p=0.011]. High-sensitivity CRP levels and a low plasma EPA/AA ratio could independently predict the prevalence of complex coronary lesions on multivariate logistic regression analysis [odds ratio 1.83 (95% CI 1.03-3.25), p=0.038 and odds ratio 2.10 (95% CI 1.11-3.94), p=0.02)]. Conclusion In patients with sAP, a low plasma EPA/AA ratio was significantly associated with a high prevalence of complex coronary lesions.

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