Hiroshi Ito

Okayama University, Okayama, Okayama, Japan

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Publications (519)2325.39 Total impact

  • Journal of the Physical Society of Japan 12/2015; 84(12):123801. DOI:10.7566/JPSJ.84.123801 · 1.59 Impact Factor
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    ABSTRACT: Background: A therapeutic strategy in patients with atrial septal defect (ASD) and significant pulmonary arterial hypertension (PAH) remains controversial. This study aimed to assess the effect of PAH-specific medications and subsequent transcatheter shunt closure (ie, a treat and repair strategy) in these patients.Methods and Results:Among 646 patients with ASD, 22 patients (mean age of 56±20 years) who had PAH [mean pulmonary artery pressure ≥25 mmHg and pulmonary vascular resistance (PVR) ≥3 Wood units] underwent successful transcatheter ASD closure. Prior to the procedure, 8 patients received PAH-specific medications (PHM group) and 14 patients did not (non-PHM group). Initially, the PHM group had higher PVR compared with non-PHM group (9.6±3.8 vs. 4.2±1.0 Wood units, P<0.01). After treatment with PAH-specific medications, PVR in this group decreased to 4.0±0.8 Wood units (P<0.01). No adverse events were observed in either the PHM or non-PHM group during or after the transcatheter procedure. In the PHM group, during a treatment period of 52±48 months, the World Health Organization Functional Classification significantly improved (3.0±0.5 to 2.0±0.0, P<0.01), as well as in the non-PHM group (2.1±0.6 to 1.5±0.5, P<0.01). Conclusions: Treat and repair strategy provided substantial improvement and no worsening of the WHO-FC, even in patients with ASD and significant PAH. Long-term hemodynamic follow-up is mandatory to evaluate the ultimate efficacy and safety of this new strategy.
    Circulation Journal 11/2015; DOI:10.1253/circj.CJ-15-0599 · 3.94 Impact Factor
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    ABSTRACT: Background: Brugada syndrome (BrS)-type electrocardiogram (ECG) is concealed by complete right bundle-branch block (CRBBB) in some cases of BrS. Clinical significance of BrS masked by CRBBB is not well known.Methods and Results:We reviewed an ECG database of 326 BrS patients who had type 1 ECG with or without pilsicainide. "BrS masked by CRBBB" was defined on ECG as <2-mm elevation of the J point at the time of CRBBB in the right precordial leads, and BrS-type J-point elevation ≥2 mm at the time of normalized QRS complex on relieved CRBBB. We identified 25 BrS patients (7.7%) with persistent (n=12) or intermittent CRBBB (n=13). Relief of CRBBB by pacing was performed in patients with persistent CRBBB. The prevalence of BrS masked by CRBBB was 3.1% (10/326 patients). Three patients had type 1 ECG, and 7 patients had type 2 or 3 ECG on relief of CRBBB. Two of these 10 patients had lethal arrhythmic events during the follow-up period (mean, 86.4±57.2 months). There was no prognostic difference between BrS masked by CRBBB and other BrS. Conclusions: In a small BrS population, CRBBB can completely mask typical BrS-type ECG. BrS masked by CRBBB is associated with the same risk of fatal ventricular tachyarrhythmia as other BrS.
    Circulation Journal 10/2015; DOI:10.1253/circj.CJ-15-0618 · 3.94 Impact Factor
  • Shin Makabe · Hiroyuki Watanabe · Hiroshi Ito ·

  • Journal of the American College of Cardiology 10/2015; 66(15):B12. DOI:10.1016/j.jacc.2015.08.074 · 16.50 Impact Factor

  • Takashi Koyama · Hiroyuki Watanabe · Hiroshi Ito ·

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    ABSTRACT: Background: Endothelial function is a prognostic predictor in patients undergoing percutaneous coronary intervention (PCI). However, in an era with widespread use of drug-eluting stents, the clinical relevance of endothelial dysfunction on restenosis in patients undergoing PCI has not been fully evaluated. Methods: This study included 80 patients with stable angina pectoris. Flow-mediated dilation (FMD) of the brachial artery was examined 1 week after PCI. Patients were retrospectively followed-up for an average of 21 months after PCI. The primary endpoints included cardiac death, nonfatal myocardial infarction, stroke, coronary revascularization, and critical limb ischemia. Results: A drug-eluting stent was used in 58 patients and a cardiovascular event was recorded in 34 patients during follow-up. The incidence of all cardiovascular diseases was significantly greater in the low FMD (median FMD <4.2 %) than the high FMD (median FMD ≥4.2 %) group (60 % vs. 25 %, p <0.01). Furthermore, the incidence of coronary revascularization was significantly higher in the low than the high FMD group (p = 0.02), while the incidence of in-stent restenosis did not differ between the two groups. Cox regression analysis showed that low FMD was an independent predictor of cardiovascular events (hazard ratio: 2.77, 95 % confidence interval: 1.23 to 6.19, p = 0.01). Conclusions: Impaired brachial artery FMD independently predicts long-term cardiovascular events after PCI in the era of drug-eluting stents.
    BMC Cardiovascular Disorders 09/2015; 15(1):102. DOI:10.1186/s12872-015-0096-z · 1.88 Impact Factor
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    ABSTRACT: Background: Establishment of a biological pacemaker is expected to solve the persisting problems of a mechanical pacemaker including the problems of battery life and electromagnetic interference. Enhancement of the funny current (If) flowing through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and attenuation of the inward rectifier K+ current (IK1) flowing through inward rectifier potassium (Kir) channels are essential for generation of a biological pacemaker. Therefore, we generated HCN4-overexpressing mouse embryonic stem cells (mESCs) and induced cardiomyocytes that originally show poor IK1 currents, and we investigated whether the HCN4-overexpressing mESC-derived cardiomyocytes (mESC-CMs) function as a biological pacemaker in vitro. Methods and results: The rabbit Hcn4 gene was transfected into mESCs, and stable clones were selected. mESC-CMs were generated via embryoid bodies and purified under serum/glucose-free and lactate-supplemented conditions. Approximately 90% of the purified cells were troponin I-positive by immunostaining. In mESC-CMs, expression level of the Kcnj2 gene encoding Kir2.1, which is essential for generation of IK1 currents that are responsible for stabilizing the resting membrane potential, was lower than that in an adult mouse ventricle. HCN4-overexpressing mESC-CMs expressed about a 3-times higher level of the Hcn4 gene than did non-overexpressing mESC-CMs. Expression of the Cacna1h gene, which encodes T-type calcium channel and generates diastolic depolarization in the sinoatrial node, was also confirmed. Additionally, genes required for impulse conduction including Connexin40, Connexin43, and Connexin45 genes, which encode connexins forming gap junctions, and the Scn5a gene, which encodes sodium channels, are expressed in the cells. HCN4-overexpressing mESC-CMs showed significantly larger If currents and more rapid spontaneous beating than did non-overexpressing mESC-CMs. The beating rate of HCN4-overexpressing mESC-CMs responded to ivabradine, an If inhibitor, and to isoproterenol, a beta-adrenergic receptor agonist. Co-culture of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with aggregates composed of mESC-CMs resulted in synchronized contraction of the cells. The beating rate of hiPSC-CMs co-cultured with aggregates of HCN4-overexpressing mESC-CMs was significantly higher than that of non-treated hiPSC-CMs and that of hiPSC-CMs co-cultured with aggregates of non-overexpressing mESC-CMs. Conclusions: We generated HCN4-overexpresssing mESC-CMs expressing genes required for impulse conduction, showing rapid spontaneous beating, responding to an If inhibitor and beta-adrenergic receptor agonist, and having pacing ability in an in vitro co-culture system with other excitable cells. The results indicated that these cells could be applied to a biological pacemaker.
    PLoS ONE 09/2015; 10(9):e0138193. DOI:10.1371/journal.pone.0138193 · 3.23 Impact Factor
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    ABSTRACT: The goal of this study was to examine the diagnostic performance of noninvasive fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFRCT) in relation to coronary calcification severity. FFRCT has shown promising results in identifying lesion-specific ischemia. The extent to which the severity of coronary calcification affects the diagnostic performance of FFRCT is not known. Coronary calcification was assessed by using the Agatston score (AS) in 214 patients suspected of having coronary artery disease who underwent coronary CTA, FFRCT, and FFR (FFR examination was performed in 333 vessels). The diagnostic performance of FFRCT (≤0.80) in identifying vessel-specific ischemia (FFR ≤0.80) was investigated across AS quartiles (Q1 to Q4) and for discrimination of ischemia in patients and vessels with a low-mid AS (Q1 to Q3) versus a high AS (Q4). Coronary CTA stenosis was defined as lumen reduction >50%. Mean ± SD per-patient and per-vessel AS were 302 ± 468 (range 0 to 3,599) and 95 ± 172 (range 0 to 1,703), respectively. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of FFRCT across AS quartiles. Discrimination of ischemia by FFRCT was high in patients with a high AS (416 to 3,599) and a low-mid AS (0 to 415), with no difference in area under the receiver-operating characteristic curve (AUC) (0.86 [95% confidence interval (CI): 0.76 to 0.96] vs. 0.92 [95% CI: 0.88 to 0.96]) (p = 0.45). Similarly, discrimination of ischemia by FFRCT was high in vessels with a high AS (121 to 1,703) and a low-mid AS (0 to 120) (AUC: 0.91 [95% CI: 0.85 to 0.97] vs. 0.95 [95% CI: 0.91 to 0.98]; p = 0.65). Diagnostic accuracy and specificity of FFRCT were significantly higher than for stenosis assessment in each AS quartile at the per-patient (p < 0.001) and per-vessel (p < 0.05) level with similar sensitivity. In vessels with a high AS, FFRCT exhibited improved discrimination of ischemia compared with coronary CTA alone (AUC: 0.91 vs. 0.71; p = 0.004), whereas on a per-patient level, the difference did not reach statistical significance (AUC: 0.86 vs. 0.72; p = 0.09). FFRCT provided high and superior diagnostic performance compared with coronary CTA interpretation alone in patients and vessels with a high AS. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    JACC. Cardiovascular imaging 08/2015; 8(9). DOI:10.1016/j.jcmg.2015.06.003 · 7.19 Impact Factor
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    ABSTRACT: The presence of coronary artery calcification (CAC) and its severity predict future cardiovascular events and is used for risk stratification. However, the association of CAC with heart failure (HF) in patients without a history of coronary artery disease (CAD) remains unclear. This study aimed to determine the correlations of CAC with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and HF events in patients without a history of CAD or HF. From June 2010 to June 2013, a total of 487 patients without a history of CAD and HF were enrolled. All of the patients underwent plane multi-detector computed tomography. They were divided into four categories according to CAC scores: ≤10, 11-100, 101-400, and ≥401. The proportion of patients with high NT-proBNP levels increased with CAC categories (p<0.0001). The CAC score was associated with NT-proBNP levels ≥400pg/ml, with an odds ratio of 2.901 (95% confidence interval: 1.368-6.151, p=0.0055) for CAC scores ≥401 compared with CAC scores of 0-10 after adjustment for confounding factors. During the follow-up period of 497±315 days, nine patients were admitted for HF. Kaplan-Meier analysis showed that patients with CAC scores ≥401 had a lower rate of freedom from admission for HF with cumulative incidences of 0.4%, 1%, 2%, and 8% for CAC scores of 0-10, 11-100, 101-400, and ≥401, respectively (p<0.0001). Increasing CAC scores were associated with an increase in incidence of admission for HF, with a hazard ratio of 10.371 for CAC scores ≥401 (95% CI: 1.062-101.309, p=0.0443) compared with CAC scores of 0-10 after adjustment for risk factors. Severe CAC is an independent determinant of high NT-proBNP levels and a predictor of admission for HF in a population without a history of CAD or HF. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
    Journal of Cardiology 08/2015; DOI:10.1016/j.jjcc.2015.06.014 · 2.78 Impact Factor

  • Respiratory Investigation 08/2015; 53(6). DOI:10.1016/j.resinv.2015.06.004
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    Takashi Koyama · Hiroyuki Watanabe · Hiroshi Ito ·
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    ABSTRACT: Earlobe creases (ELC) are frequently observed in patients with atherosclerosis. Atherosclerosis is considered to be a systemic vascular inflammatory disease, and oxidative stress is known to be a contributor to vascular inflammation. It is well known that inflammatory biomarkers [high-sensitivity C-reactive protein (hs-CRP), pentraxin3 (PTX3)] and oxidative stress markers [malondialdehyde low-density lipoprotein (MDA-LDL)] are associated with atherosclerotic changes. This study was designed to test the hypothesis that biomarkers of inflammation and oxidative stress are increased in patients with ELC. A total of 223 consecutive patients with atherosclerotic risk factors were enrolled and divided into two groups. One group consisted of patients with ELC (ELC group, n=134) and the other was without ELC (non-ELC group, n=89). Medical information and biomarker levels related to atherosclerosis were acquired from these patients. The male ratio, prevalence of hypertension, diabetes mellitus, and MDA-LDL, hs-CRP, and PTX3 levels were found to be higher in the ELC group, compared with the non-ELC group. A multiple logistic regression analysis showed that PTX3 levels, rather than hs-CRP, constituted the strongest predictive factor for the appearance of ELC. Vascular inflammation and oxidative stress are associated with the presence of ELC. Copyright © 2015. Published by Elsevier Ltd.
    Journal of Cardiology 07/2015; DOI:10.1016/j.jjcc.2015.06.002 · 2.78 Impact Factor
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    ABSTRACT: Nonalcoholic fatty liver disease is associated with a risk of coronary artery disease (e.g., diabetes mellitus, dyslipidemia, metabolic syndrome). We evaluated whether nonalcoholic hepatic steatosis is associated with high-risk plaques as assessed by multidetector computed tomography (CT). This retrospective study involved 414 participants suspected of having coronary artery disease. Nonalcoholic hepatic steatosis was defined as a liver-to-spleen fat ratio of <1.0 and the presence and appropriate characteristics of coronary-artery plaques as assessed by coronary CT angiography. High-risk plaques were identified, as were low-density plaques, positive remodeling, and spotty calcification. Compared with patients who did not have nonalcoholic hepatic steatosis, patients with nonalcoholic hepatic steatosis had more low-density plaques (21% vs. 44%, p<0.01), positive remodeling (41% vs. 58%, p = 0.01), and spotty calcification (12% vs. 36%, p<0.01). The number of high-risk plaques in patients with nonalcoholic hepatic steatosis was greater than in those without nonalcoholic hepatic steatosis (p<0.01). Patients with nonalcoholic hepatic steatosis were more likely to have high-risk plaques than were those with only an elevated level of visceral adipose tissue (≥86 cm2; 35% vs. 16%, p<0.01). Multivariate analyses that included nonalcoholic hepatic steatosis, amount of visceral adipose tissue, and the presence/absence of traditional risk factors demonstrated that nonalcoholic hepatic steatosis was an independent predictor of high-risk plaques (odds ratio: 4.60; 95% confidence interval: 1.94-9.07, p<0.01). Diagnosis of nonalcoholic hepatic steatosis may be of value when assessing the risk of coronary artery disease.
    PLoS ONE 06/2015; 10(6):e0131138. DOI:10.1371/journal.pone.0131138 · 3.23 Impact Factor
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    ABSTRACT: Left ventricular (LV) diastolic dysfunction is frequently observed in patients with type 2 diabetes. Dipeptidyl peptidase-4 inhibitor (DPP-4i) attenuates postprandial hyperglycemia (PPH) and may have cardio-protective effects. It remains unclear whether DPP-4i improves LV diastolic function in patients with type 2 diabetes, and, if so, it is attributable to the attenuation of PPH or to a direct cardiac effect of DPP-4i. We compared the effects of the DPP-4i, sitagliptin, and the alpha-glucosidase inhibitor, voglibose, on LV diastolic function in patients with type 2 diabetes. We conducted a prospective, randomized, open-label, multicenter study of 100 diabetic patients with LV diastolic dysfunction. Patients received sitagliptin (50 mg/day) or voglibose (0.6 mg/day). The primary endpoints were changes in the e' velocity and E/e' ratio from baseline to 24 weeks later. The secondary efficacy measures included HbA1c, GLP-1, lipid profiles, oxidative stress markers and inflammatory markers. The study was completed with 40 patients in the sitagliptin group and 40 patients in the voglibose group. There were no significant changes in the e' velocity and E/e' ratio from baseline to 24 weeks later in both groups. However, analysis of covariance demonstrated that pioglitazone use is an independent factor associated with changes in the e' and E/e' ratio. Among patients not using pioglitazone, e' increased and the E/e' ratio decreased in both the sitagliptin and voglibose groups. GLP-1 level increased from baseline to 24 weeks later only in the sitagliptin group (4.8 ± 4.7 vs. 7.3 ± 5.5 pmol/L, p < 0.05). The reductions in HbA1c and body weight were significantly greater in the sitagliptin group than in the voglibose group (-0.7 ± 0.6 % vs. -0.3 ± 0.4, p < 0.005; -1.3 ± 3.2 kg vs. 0.4 ± 2.8 kg, p < 0.05, respectively). There were no changes in lipid profiles and inflammatory markers in both groups. Our trial showed that sitagliptin reduces HbA1c levels more greatly than voglibose does, but that neither was associated with improvement in the echocardiographic parameters of LV diastolic function in patients with diabetes. Registered at http://www.umin.ac.jp under UMIN000003784.
    Cardiovascular Diabetology 06/2015; 14(1):83. DOI:10.1186/s12933-015-0242-z · 4.02 Impact Factor
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    ABSTRACT: Recent clinical trials have demonstrated the efficacy of short-term treatment with tolvaptan, an oral vasopressin V2 receptor antagonist, in patients with heart failure. However, the response to tolvaptan varies among patients. The aim of this study was to determine factors associated with response to tolvaptan in patients with acute decompensated heart failure (ADHF). The Tolvaptan Registry, a prospective, observational, multicenter cohort study performed in Japan, aims to determine factors affecting the responsiveness of tolvaptan in patients with ADHF. We enrolled ADHF patients treated with tolvaptan and they were divided into two groups: responders and non-responders. Responders were defined as subjects who met all of the following three conditions: (1) increasing urine volume during a 24-hour period after the start of tolvaptan treatment; (2) improvement in New York Heart Association functional class; and (3) decrease in cardiothoracic ratio assessed by chest X-ray on day 3 of tolvaptan administration. Among the 114 patients, treatment with tolvaptan improved three conditions of heart failure in more than half of all the cohorts (71 patients, 62%). As for baseline characteristics, estimated glomerular filtration rate, urine osmolality, and kidney size were significantly greater in responders than in non-responders. Multivariate logistic analysis revealed that kidney size was independently associated with responders (odds ratio: 1.083, p=0.001, 95% confidence interval 1.031-1.137). The main clinical characteristic of responders to treatment with tolvaptan is that kidney size is preserved. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.
    Journal of Cardiology 06/2015; DOI:10.1016/j.jjcc.2015.04.017 · 2.78 Impact Factor

  • Nature Physics 06/2015; DOI:10.1038/nphys3359 · 20.15 Impact Factor
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    ABSTRACT: Pulmonary arterial hypertension (PAH) is characterized by elevation of pulmonary artery pressure caused by pulmonary vasoconstriction and vascular remodeling, which leads to right heart failure and death. Epoprostenol (prostaglandin I2) has a potent short-acting vasodilator property, and intravenous continuous epoprostenol is therefore used for treatment of PAH. Here we review evidence for the usefulness of intravenous continuous epoprostenol therapy in patients with PAH. Epoprostenol therapy is effective in idiopathic PAH patients and in patients with PAH associated with connective tissue disease, portal hypertension or congenital heart diseases, but it is not effective in patients with pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis. High-dose epoprostenol therapy markedly improved hemodynamics in some patients with PAH, possibly due to reverse remodeling of pulmonary arteries. This therapy has several side effects and complications such as headache, hypotension and catheter-related infections. Intravenous continuous epoprostenol is an effective treatment, but there are still some problems to be resolved.
    Acta medica Okayama 06/2015; 69(3):129-36. · 0.70 Impact Factor

Publication Stats

8k Citations
2,325.39 Total Impact Points


  • 2009-2015
    • Okayama University
      • Department of Cardiovascular Medicine
      Okayama, Okayama, Japan
  • 2005-2015
    • Akita University
      • • Department of Cardiovascular and Respiratory Medicine
      • • First Department of Internal Medicine
      Akita, Akita, Japan
  • 2004-2014
    • Osaka City University
      • • Graduate School of Medicine
      • • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan
    • Nagoya University
      • • Graduate School of Engineering
      • • Research Center for Materials Science
      Nagoya, Aichi, Japan
  • 2013
    • Saitama Medical University
      • Center for Maternal, Fetal and Neonatal Medicine
      Saitama, Saitama, Japan
  • 2006-2012
    • Akita University Hospital
      Akita, Akita, Japan
  • 1992-2011
    • Sakurabashi Watanabe Hospital
      Ōsaka, Ōsaka, Japan
  • 2008
    • Juntendo University
      Edo, Tōkyō, Japan
  • 1995-2007
    • Yamaguchi University
      • • Department of Medical Bioregulation
      • • Yamaguchi University Hospital
      Yamaguti, Yamaguchi, Japan
    • Himeji Institute of Technology
      • Department of Material Science
      Himezi, Hyōgo, Japan
  • 2004-2006
    • Massachusetts General Hospital
      • Transplantation Biology Research Center
      Boston, MA, United States
  • 2003
    • Musashino Red Cross Hospital
      Edo, Tōkyō, Japan
  • 1991-2002
    • Tokyo Medical and Dental University
      • • Department of Cardiovascular Medicine
      • • Department of Internal Medicine
      • • Department of Medicine
      Edo, Tōkyō, Japan
  • 1991-1997
    • Kyoto University
      • Department of Physics II
      Kioto, Kyōto, Japan