Hiroshi Ito

Okayama University, Okayama, Okayama, Japan

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Publications (212)728.6 Total impact

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    ABSTRACT: RIPC reduced acute kidney injury after emergency percutaneous coronary intervention.•RIPC was safe and was an easy strategy in real clinical settings.•RIPC is a promising strategy in patients with ST-elevation myocardial infarction.
    International Journal of Cardiology. 01/2015; 178.
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    ABSTRACT: Postprandial hypertriglyceridemia impairs endothelial function and plays an important role in the development of atherosclerosis. The aim of the present study was to examine the postprandial effects of the dipeptidyl peptidase-4 inhibitor vildagliptin and the α-glucosidase inhibitor voglibose on endothelial dysfunction and lipid profiles following a single administration. A randomized cross-over trial using 11 normoglycemic individuals was performed. The postprandial effects of a single administration of vildagliptin (50 mg) or voglibose (0.3 mg) on endothelial function were analyzed using brachial artery flow-mediated dilation (FMD) and lipid profiles during fasting and 1.5 and 3 h after an oral cookie-loading test. Compared with voglibose, vildagliptin significantly suppressed postprandial endothelial dysfunction, (%FMD, -1.6±0.9 vildagliptin vs. -4.0±0.7 voglibose; P=0.01) and the postprandial incremental increase in the triglyceride level (28±18 vildagliptin vs. 51±26 mg/dl voglibose; P=0.01) 3 h after a cookie-loading test. In addition, vildagliptin significantly increased the levels of glucagon-like peptide-1 compared with voglibose 3 h after a loading cookie test (4.4±0.6 vs. 2.9±0.7 pmol/l, respectively; P=0.04). No significant differences in the levels of glucose, apolipoprotein B-48, glucagon or insulin were observed between vildagliptin and voglibose treatments. In conclusion, a single administration of vildagliptin attenuated postprandial endothelial dysfunction and postprandial hypertriglyceridemia, suggesting that vildagliptin may be a promising antiatherogenic agent.
    Experimental and therapeutic medicine 01/2015; 9(1):84-88. · 0.34 Impact Factor
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    ABSTRACT: Background:Recently, a non-invasive method using computational fluid dynamics to calculate vessel-specific fractional flow reserve (FFRCT) from routinely acquired coronary computed tomography angiography (CTA) was described. The Analysis of Coronary Blood Flow Using CT Angiography: Next Steps (NXT) trial, which was a prospective, multicenter trial including 254 patients with suspected coronary artery disease, noted high diagnostic performance of FFRCTcompared with invasive FFR. The aim of this post-hoc analysis was to assess the diagnostic performance of non-invasive FFRCTvs. standard stenosis quantification on coronary CTA in the Japanese subset of the NXT trial.Methods and Results:A total of 57 Japanese participants were included from Okayama University (n=36), Kyoto University (n=17), and Keio University (n=4) Hospitals. Per-patient diagnostic accuracy of FFRCT(74%; 95% confidence interval [CI]: 60-85%) was higher than for coronary CTA (47%; 95% CI: 34-61%, P<0.001) arising from improved specificity (63% vs. 27%, P<0.001). FFRCTcorrectly reclassified 53% of patients and 63% of vessels with coronary CTA false positives as true negatives. When patients with Agatston score >1,000 were excluded, per-patient accuracy of FFRCTwas 83% with a high specificity of 76%, similar to the overall NXT trial findings.Conclusions:FFRCThas high diagnostic performance compared with invasive FFR in the Japanese subset of patients in the NXT trial.
    Circulation journal : official journal of the Japanese Circulation Society. 12/2014;
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    ABSTRACT: Although high-degree atrioventricular block (AVB) is a common initial manifestation of cardiac sarcoidosis, little is known about the outcomes. The aim of this study was to assess outcomes in patients with AVB as an initial manifestation of cardiac sarcoidosis compared with those in patients with ventricular tachyarrhythmia (VT) and/or heart failure (HF). Fifty-three consecutive patients with cardiac sarcoidosis, who had high-degree AVB (n = 22) or VT and/or HF (n = 31), were enrolled. The end point was defined as major adverse cardiac events, including cardiac death, ventricular fibrillation, sustained VT, and hospitalization for HF. Over a median follow-up period of 34 months, the outcomes of major adverse cardiac events were better in patients with high-degree AVB than in those with VT and/or HF (log-rank test, p = 0.046). However, this difference was due mainly to HF hospitalization. The outcomes of fatal cardiac events, including cardiac death, ventricular fibrillation, and sustained VT, were comparable between the 2 groups (log-rank test, p = 0.877). The fatal cardiac events in patients with high-degree AVB were not associated with the initiation of steroid treatment or left ventricular dysfunction. In conclusion, the outcomes of major adverse cardiac events are better in patients with high-degree AVB than in those with VT and/or HF. However, patients with high-degree AVB have a high rate of fatal cardiac events, similar to those with VT and/or HF. An indication for an implantable cardioverter-defibrillator, but not a pacemaker system, can be considered in patients with cardiac sarcoidosis manifested by high-degree AVB. Copyright © 2014 Elsevier Inc. All rights reserved.
    The American journal of cardiology. 11/2014;
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    ABSTRACT: Background:Risk stratification in patients with Brugada syndrome for primary prevention of sudden cardiac death is still an unsettled issue. A recent consensus statement suggested the indication of implantable cardioverter defibrillator (ICD) depending on the clinical risk factors present (spontaneous type 1 Brugada electrocardiogram (ECG) [Sp1], history of syncope [syncope], and ventricular fibrillation during programmed electrical stimulation [PES+]). The indication of ICD for the majority of patients, however, remains unclear.Methods and Results:A total of 218 consecutive patients (211 male; aged 46±13 years) with a type 1 Brugada ECG without a history of cardiac arrest who underwent evaluation for ICD including electrophysiological testing were examined retrospectively. During a mean follow-up period of 78 months, 26 patients (12%) developed arrhythmic events. On Kaplan-Meier analysis patients with each of Sp1, syncope, or PES+ suffered arrhythmic events more frequently (P=0.018, P<0.001, and P=0.003, respectively). On multivariate analysis Sp1 and syncope were independent predictors of arrhythmic events. When dividing patients according to the number of these 3 risk factors present, patients with 2 or 3 risk factors experienced arrhythmic events more frequently than those with 0 or 1 risk factor (23/93 vs. 3/125; P<0.001).Conclusions:Syncope, Sp1, and PES+ are important risk factors and the combination of these risks well stratify the risk of later arrhythmic events.
    Circulation journal : official journal of the Japanese Circulation Society. 11/2014;
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    ABSTRACT: Postprandial elevation of triglycerides impairs endothelial function and contributes to the development of atherosclerosis. We investigated the effects of omega-3 fatty acids on postprandial endothelial function and lipid profiles.
    Biomedicine & Pharmacotherapy. 10/2014;
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    ABSTRACT: Objective We examined whether early loading of eicosapentaenoic acid (EPA) reduces clinical adverse events by 1 month, accompanied by a decrease in C-reactive protein (CRP) values in patients with acute myocardial infarction (MI). Background Acute MI triggers an inflammatory reaction, which plays an important role in myocardial injury. EPA could attenuate the inflammatory response. Methods This prospective, open-label, blinded endpoint, randomized trial consisted of 115 patients with acute MI. They were randomly assigned to the EPA group (57 patients) and the control group (58 patients). After percutaneous coronary intervention (PCI), 1800 mg/day of EPA was initiated within 24 h. The primary endpoint was composite events, including cardiac death, stroke, re-infarction, ventricular arrhythmias, and paroxysmal atrial fibrillation within 1 month. Results Administration of EPA significantly reduced the primary endpoint within 1 month (10.5 vs 29.3%, p = 0.01), especially the incidence of ventricular arrhythmias (7.0 vs 20.6%, p = 0.03). Peak CRP values after PCI in the EPA group were significantly lower than those in the control group (median [interquartile range], 8.2 [5.6–10.2] mg/dl vs 9.7 [7.6–13.9] mg/dl, p < 0.01). Logistic regression analysis showed that EPA use was an independent factor related to ventricular arrhythmia until 1 month, with an odds ratio of 0.29 (95% confidence interval, 0.09 to 0.96, p = 0.04). Conclusions Early EPA treatment after PCI in the acute stage of MI reduces the incidence of ventricular arrhythmias, and lowers CRP values.
    International Journal of Cardiology 10/2014; 176(3):577–582. · 6.18 Impact Factor
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    ABSTRACT: Transcatheter closure of complex multiple atrial septal defects (ASDs) remains a challenge. We describe our clinical experience with staged device deployment in a patient with multiple ASDs using four Amplatzer septal occluder devices. Three-dimensional transesophageal echocardiography imaging contributed not only to the therapeutic guidance of successful device deployment but also to the decision making for the staged device delivery approach in a case of morphologically complex multiple ASDs.
    Echocardiography 09/2014; · 1.26 Impact Factor
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    ABSTRACT: Background Alpha glucosidase inhibitor (GI) attenuates postprandial hyperglycemia (PPH) and reduces the risk of cardiovascular events in patients with impaired glucose tolerance or type 2 diabetes. Dipeptidyl peptidase 4 (DPP-4) inhibitors also attenuate PPH. PPH is one of the factors leading to endothelial dysfunction which is an early event in the pathogenesis of atherosclerosis. Furthermore, DPP-4 inhibitors protect endothelial function through a GLP-1-dependent mechanism. However, the impact of these two types of drugs on endothelial dysfunction in patients with type 2 diabetes has not been fully elucidated. We compared the effects of sitagliptin, a DPP-4 inhibitor, and voglibose, an alpha GI, on endothelial function in patients with diabetes.Methods We conducted a randomized prospective multicenter study in 66 patients with type 2 diabetes who did not achieve the treatment goal with sulfonylurea, metformin or pioglitazone treatment; 31 patients received sitagliptin treatment and 35 patients, voglibose treatment. The flow-mediated dilatation (FMD) of the brachial artery was measured in the fasting state at baseline and after 12 weeks of treatment. The primary endpoint was a change in FMD (¿FMD) from the baseline to the end of follow-up. The effects of sitagliptin and voglibose on FMD were assessed by ANCOVA after adjustment for the baseline FMD, age, sex, current smoking, diabetes duration and body mass index. Secondary efficacy measures included changes in HbA1c, GIP, GLP-1, C-peptide, CD34, lipid profile, oxidative stress markers, inflammatory markers and eGFR and any adverse events.Results¿FMD was significantly improved after 12 weeks of treatment in both groups, and there was no significant difference in ¿FMD between the two groups. There were no significant differences in changes in HbA1c, GIP, GLP-1, C-peptide, lipid profile, oxidative stress marker, inflammatory marker and eGFR between the two groups. Compared with voglibose, sitagliptin significantly increased the circulating CD34, a marker of endothelial progenitor cells. Adverse events were observed in 5 patients in only the voglibose group (diarrhea 1, nausea 1, edema 2 and abdominal fullness 1).Conclusions Sitagliptin improved endothelial dysfunction just as well as voglibose in patients with type 2 diabetes. Sitagliptin had protective effects on endothelial function without adverse events.Trial registrationregistered at http://www.umin.ac.jp/ctrj/ under UMIN000003951.
    Cardiovascular Diabetology 07/2014; 13(1):110. · 4.21 Impact Factor
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    ABSTRACT: The genetic basis of hypoplastic left heart syndrome (HLHS) remains unknown, and the lack of animal models to reconstitute the cardiac maldevelopment has hampered the study of this disease. This study investigated the altered control of transcriptional and epigenetic programs that may affect the development of HLHS by using disease-specific induced pluripotent stem (iPS) cells. Cardiac progenitor cells (CPCs) were isolated from patients with congenital heart diseases to generate patient-specific iPS cells. Comparative gene expression analysis of HLHS- and biventricle (BV) heart-derived iPS cells was performed to dissect the complex genetic circuits that may promote the disease phenotype. Both HLHS- and BV heart-derived CPCs were reprogrammed to generate disease-specific iPS cells, which showed characteristic human embryonic stem cell signatures, expressed pluripotency markers, and could give rise to cardiomyocytes. However, HLHS-iPS cells exhibited lower cardiomyogenic differentiation potential than BV-iPS cells. Quantitative gene expression analysis demonstrated that HLHS-derived iPS cells showed transcriptional repression of NKX2-5, reduced levels of TBX2 and NOTCH/HEY signaling, and inhibited HAND1/2 transcripts compared with control cells. Although both HLHS-derived CPCs and iPS cells showed reduced SRE and TNNT2 transcriptional activation compared with BV-derived cells, co-transfection of NKX2-5, HAND1, and NOTCH1 into HLHS-derived cells resulted in synergistic restoration of these promoters activation. Notably, gain- and loss-of-function studies revealed that NKX2-5 had a predominant impact on NPPA transcriptional activation. Moreover, differentiated HLHS-derived iPS cells showed reduced H3K4 dimethylation as well as histone H3 acetylation but increased H3K27 trimethylation to inhibit transcriptional activation on the NKX2-5 promoter. These findings suggest that patient-specific iPS cells may provide molecular insights into complex transcriptional and epigenetic mechanisms, at least in part, through combinatorial expression of NKX2-5, HAND1, and NOTCH1 that coordinately contribute to cardiac malformations in HLHS.
    PLoS ONE 07/2014; 9(7):e102796. · 3.53 Impact Factor
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    ABSTRACT: Percutaneous coronary intervention (PCI) based on fractional flow reserve (FFRcath) measurement during invasive coronary angiography (CAG) results in improved patient outcome and reduced healthcare costs. FFR can now be computed non-invasively from standard coronary CT angiography (cCTA) scans (FFRCT). The purpose of this study is to determine the potential impact of non-invasive FFRCT on costs and clinical outcomes of patients with suspected coronary artery disease in Japan. Clinical data from 254 patients in the HeartFlowNXT trial, costs of goods and services in Japan, and clinical outcome data from the literature were used to estimate the costs and outcomes of 4 clinical pathways: (1) CAG-visual guided PCI, (2) CAG-FFRcath guided PCI, (3) cCTA followed by CAG-visual guided PCI, (4) cCTA-FFRCT guided PCI. The CAG-visual strategy demonstrated the highest projected cost ($10,360) and highest projected 1-year death/myocardial infarction rate (2.4 %). An assumed price for FFRCT of US $2,000 produced equivalent clinical outcomes (death/MI rate: 1.9 %) and healthcare costs ($7,222) for the cCTA-FFRCT strategy and the CAG-FFRcath guided PCI strategy. Use of the cCTA-FFRCT strategy to select patients for PCI would result in 32 % lower costs and 19 % fewer cardiac events at 1 year compared to the most commonly used CAG-visual strategy. Use of cCTA-FFRCT to select patients for CAG and PCI may reduce costs and improve clinical outcome in patients with suspected coronary artery disease in Japan.
    Cardiovascular Intervention and Therapeutics 07/2014;
  • International journal of cardiology. 07/2014;
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    ABSTRACT: Residual risk of cardiovascular disease from increased small dense low-density lipoprotein (sdLDL)-cholesterol levels and low n-3 polyunsaturated fatty acid (PUFA) levels is a considerable therapeutic issue. The purpose of this study was to evaluate the effect of ezetimibe as an add-on to statins and supplemental eicosapentaenoic acid (EPA) on sdLDL cholesterol and absorption of EPA in patients with coronary artery disease.
    American journal of cardiovascular drugs : drugs, devices, and other interventions. 06/2014;
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    ABSTRACT: No study has investigated whether pioglitazone (an agonist of peroxisome proliferator-activated receptor gamma) protects against ischemia and reperfusion (IR)-induced endothelial dysfunction in humans.
    Journal of Cardiovascular Pharmacology 05/2014; · 2.38 Impact Factor
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    ABSTRACT: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by pulmonary vascular remodeling. We have reported that high-dose prostaglandin I2 (PGI2) therapy markedly improved hemodynamics in IPAH patients and that PGI2 induced apoptosis of pulmonary artery smooth muscle cells obtained from IPAH patients. PGI2 is thought to have reverse remodeling effects, although it has not been histologically confirmed. In a case series, we examined the reverse pulmonary vascular remodeling effects of PGI2 in lung tissues obtained from an IPAH patient treated with high-dose PGI2 and an IPAH patient not treated with PGI2. Apoptotic cells were detected in small pulmonary arteries of the IPAH patient treated with high-dose PGI2 but not in those from the IPAH patient not treated with PGI2. Media of peripheral pulmonary arteries were thick in the IPAH patient not treated with PGI2. On the other hand, media of peripheral pulmonary arteries were thin in the IPAH patient treated with high-dose PGI2. The single case report suggested that high-dose PGI2 therapy has the potential for reverse pulmonary vascular remodeling by induction of apoptosis and reduction of medial hypertrophy. Accumulation of cases is needed for the application to generalized effect of high-dose PGI2. <Learning objective: Reverse pulmonary vascular remodeling would provide further improvement in patients with IPAH. High-dose PGI2 therapy has the potential for reverse pulmonary vascular remodeling in patients with IPAH.
    Journal of Cardiology Cases 05/2014;
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    ABSTRACT: Multi-detector coronary CT angiography (CCTA) can detect coronary stenosis, but it has a limited ability to evaluate myocardial perfusion. We evaluated the usefulness of first-pass CT-myocardial perfusion imaging (MPI) in combination with CCTA for diagnosing coronary artery disease (CAD). A total of 145 patients with suspected CAD were enrolled. We used 64-row multi-detector CT (Definition Flash, Siemens). The same coronary CCTA data were used for first-pass CT-MPI without drug loading. Images were reconstructed by examining the signal densities at diastole as colour maps. Diagnostic accuracy was assessed by comparison with invasive coronary angiography. First-pass CT-MPI in combination with CCTA significantly improved diagnostic performance compared with CCTA alone. With per-vessel analysis, the sensitivity, specificity, positive predictive value and negative predictive value increased from 81% to 85%, 87% to 94%, 63% to 79% and 95% to 96%, respectively. The area under the receiver operating characteristic curve for detecting CAD also increased from 0.84 to 0.89 (p=0.02). First-pass CT-MPI was particularly useful for assessing segments that could not be directly evaluated due to severe calcification and motion artefacts. First-pass CT-MPI has an additional diagnostic value for detecting coronary stenosis, in particular in patients with severe calcification.
    Heart (British Cardiac Society) 04/2014; · 5.01 Impact Factor
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    ABSTRACT: Background: Several lines of evidence suggest that atrial fibrillation (AF) may be a consequence of vascular disease. We investigated the relationship between cardio-ankle vascular index (CAVI), a new index of arterial stiffness, and the presence of paroxysmal AF (PAF). Methods and results: 181 outpatients (91 patients with PAF and 90 age- and gender-matched subjects without PAF) were analysed for their sinus rhythm. The CAVI was significantly higher in patients with PAF than in subjects without PAF (9.0±1.0 vs 8.7±0.8, p<0.01). In all subjects, the CAVI was significantly correlated with the left ventricular mass index (r=0.30, p<0.01), left atrial diameter (r=0.22, p<0.01), and augmentation index, a parameter of wave reflection (r=0.32, p<0.01), in addition to age, systolic blood pressure and pulse pressure. Logistic analysis demonstrated that the CAVI was independently associated with PAF even after adjustment for confounding factors. The adjusted OR of PAF was 1.8 for each unit increase in the CAVI (p=0.01). Conclusions: Our finding suggests that increased arterial stiffness may be involved in the maintenance of AF.
    Heart Asia. 04/2014; 6(1):59-63.
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    ABSTRACT: Rationale: Epoprostenol is a first-line therapy for pulmonary arterial hypertension (PAH) patients in WHO Functional Class IV, who often have low cardiac output and hypotension. Initiation of epoprostenol could cause hemodynamic collapse. Inotropic agent support could prevent the hemodynamic instability caused by initiation of epoprostenol, though a protocol has not been established. Objective: To assess the reliability and prognostic effects of dobutamine (DOB) and dopamine (DOA) support at the initiation of epoprostenol therapy in PAH patients. Methods: We initiated epoprostenol therapy in 71 PAH patients. Hemodynamics at the initiation of epoprostenol was measured by right heart catheterization. We initiated DOB when the patients' mixed venous oxygen saturation was <60% or cardiac index was <2.0 l/min/m2 or when right ventricular failure was clinically suspected. We initiated DOA when the patients' systolic blood pressure was <90 mmHg or urine volume was <20 ml/h. Measurements and Main Results: At the initiation of epoprostenol, DOB and/or DOA were required in 46 patients. Neither DOB nor DOA was an independent factor of poor short-term survival (DOB: HR 1.63 (95%CI: 0.33-8.11) and DOA: HR 0.22 (95%CI: 0.03-1.70)). Sixty-two patients were discharged for home infusion of epoprostenol. Transplant-free survival rates at five years were 80.0% for patients with non DOB and DOA support at the start of epoprostenol and 76.6% for patients with DOB plus/or DOA support (P=0.45). Conclusions: Temporary use of DOB and DOA is safe as support at the initiation of epoprostenol therapy in PAH patients with low cardiac output and hypotension.
    Annals of the American Thoracic Society. 04/2014;
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    ABSTRACT: Postprandial elevation of triglyceride-rich lipoproteins impairs endothelial function, which can initiate atherosclerosis. We investigated the effects of bezafibrate on postprandial endothelial dysfunction and lipid profiles in patients with metabolic syndrome. Ten patients with metabolic syndrome were treated with 400 mg/day bezafibrate or untreated for 4 weeks in a randomized crossover study. Brachial artery flow-mediated dilation (FMD) and lipid profiles were assessed during fasting and after consumption of a standardized snack. Serum triglyceride and cholesterol contents of lipoprotein fractions were analyzed by high-performance liquid chromatography. Postprandial FMD decreased significantly and reached its lowest value 4 h after the cookie test in both the bezafibrate and control groups, but the relative change in FMD from baseline to minimum in the bezafibrate group was significantly smaller than that in the control group (-29.0 +/- 5.9 vs. -42.9 +/- 6.2 %, p = 0.04). Bezafibrate significantly suppressed postprandial elevation of triglyceride (incremental area under the curve (AUC): 544 +/- 65 vs. 1158 +/- 283 mg h/dl, p = 0.02) and remnant lipoprotein cholesterol (incremental AUC: 27.9 +/- 3.5 vs. 72.3 +/- 14.1 mg h/dl, p < 0.01). High-performance liquid chromatography analysis revealed that postprandial triglyceride content of the chylomicron and very low-density lipoprotein fractions was significantly lower in the bezafibrate group than in the control group (p < 0.05). Bezafibrate significantly decreased postprandial endothelial dysfunction, and elevations of both exogenous and endogenous triglycerides in patients with metabolic syndrome, suggesting that bezafibrate may have vascular protective effects in these patients.Clinical trial registration: Unique Identifiers: UMIN000012557.
    Cardiovascular Diabetology 04/2014; 13(1):71. · 4.21 Impact Factor

Publication Stats

2k Citations
728.60 Total Impact Points

Institutions

  • 2009–2014
    • Okayama University
      • Department of Cardiovascular Medicine
      Okayama, Okayama, Japan
  • 2013
    • Hiroshima City Hospital
      Hirosima, Hiroshima, Japan
  • 2011–2013
    • Kagawa Prefectural Central Hospital
      Takamatu, Kagawa, Japan
    • Chibaken Saiseikai Narashino Hospital
      Tiba, Chiba, Japan
    • Sakakibara Heart Institute
      Фучу, Tōkyō, Japan
    • Fukaya Red Cross Hospital
      Fukaya, Saitama, Japan
  • 2004–2013
    • Osaka City University
      • • Graduate School of Medicine
      • • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan
  • 2012
    • Hyogo College of Medicine
      • Department of Internal Medicine
      Nishinomiya, Hyogo-ken, Japan
    • Nagai Internal Medicine Clinic
      Okayama, Okayama, Japan
  • 2003–2012
    • University Hospital Medical Information Network
      Edo, Tōkyō, Japan
    • Musashino Red Cross Hospital
      Edo, Tōkyō, Japan
  • 2002–2012
    • Sakurabashi Watanabe Hospital
      Ōsaka, Ōsaka, Japan
  • 2008–2011
    • Juntendo University
      Edo, Tōkyō, Japan
  • 2010
    • Minami Okayama Medical Center
      Okayama, Okayama, Japan
  • 2000–2008
    • Chiba University
      • Graduate School of Medicine
      Chiba-shi, Chiba-ken, Japan
  • 2000–2001
    • Chiba University Hospital
      Tiba, Chiba, Japan