Toru Satoh

Kyorin University, Edo, Tōkyō, Japan

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Publications (115)497.79 Total impact

  • American Journal of Respiratory and Critical Care Medicine 06/2014; 189(11):1437-9. · 11.04 Impact Factor
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    ABSTRACT: Percutaneous transluminal pulmonary angioplasty (PTPA) is a recently developed catheter-based therapy for chronic thromboembolic pulmonary hypertension (CTEPH). The aim of the present study was to investigate the safety and efficacy of PTPA in elderly patients with CTEPH.
    International journal of cardiology. 05/2014;
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    EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 04/2014; 9(12):1483. · 3.17 Impact Factor
  • European Respiratory Journal 01/2014; · 6.36 Impact Factor
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    ABSTRACT: Behçet’s disease is a rare condition sometimes associated with chronic cardiac inflammation followed by myocardial dysfunction and vascular inflammation. We report a case of recurrent right atrial thrombus due to Behçet’s disease despite continued anticoagulation therapy. The thrombus disappeared following the initiation of immunosuppressive therapy. To avoid a progression to thrombus or cardiac dysfunction in this recurrent case, the early identification of cardiac involvement of Behçet’s disease by echocardiography and/or cardiac MRI might be important. Combined immunosuppressive therapy with prednisone and cyclophosphamide might be needed to treat this recurrent thrombosis due to Behçet’s disease.
    The Canadian journal of cardiology 01/2014; · 3.12 Impact Factor
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    ABSTRACT: Pulmonary endarterectomy (PEA) is established for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). Recently, percutaneous transluminal pulmonary angioplasty (PTPA) has been added for peripheral-type CTEPH, whose lesions exist in segmental, subsegmental, and more distal pulmonary arteries. A shift in clinical practice of interventional therapies occurred in 2009 (first mainly PEA, later PTPA). We examined the latest clinical outcomes of patients with CTEPH. This study retrospectively included 136 patients with CTEPH. Twenty-nine were treated only with drug (Drug-group), and the other 107 underwent interventional therapies (Interventions-group) (39 underwent PEA [PEA-group] and 68 underwent PTPA [PTPA-group]). Total 213 PTPA sessions (failures, 0%; mortality rate, 1.47%) was performed in the PTPA-group (complications: reperfusion pulmonary edema, 7.0%; hemosputum or hemoptysis, 5.6%; vessel dissection, 2.3%; wiring perforation, 0.9%). Although baseline hemodynamic parameters were significantly more severe in the Interventions-group, the outcome after the diagnosis was much better in the Interventions-group than in the Drug-group (98% vs. 64% 5-year survival, p<0.0001). Hemodynamic improvement in the PEA-group was a 46% decrease in mean pulmonary arterial pressure (PAP) and a 49% decrease in total pulmonary resistance (TPR) (follow-up period; 74.7±32.3 months), while those in the PTPA-group were a 40% decrease in mean PAP and a 49% decrease in TPR (follow-up period; 17.4±9.3 months). The 2-year survival rate in the Drug-group was 82.0%, and the 2-year survival rate, occurrence of right heart failure, and re-vascularization rate in the PEA-group were 97.4%, 2.6%, and 2.8%, and those in the PTPA-group were 98.5%, 2.9%, and 2.9%, respectively. The patients who underwent interventional therapies had better results than those treated only with drugs. The availability of both of these operative and catheter-based interventional therapies leads us to expect the dawn of a new era of therapeutic strategies for CTEPH.
    PLoS ONE 01/2014; 9(4):e94587. · 3.73 Impact Factor
  • Annals of the American Thoracic Society. 12/2013; 10(6):726-7.
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    ABSTRACT: The presence of genetic rearrangements of bone morphogenetic protein type 2 receptor (BMPR2) was identified in pulmonary arterial hypertension (PAH) patients as the deletion or duplication of one or more exons of the gene. We recently investigated the deletion break points in exonic deletions of BMPR2 in two Japanese familial cases with PAH, and found that these were Alu-mediated via either non-allelic homologous recombination or non-homologous recombination. We herein report the third case of exonic deletion, which was in a 25-year-old female PAH patient with a deletion of BMPR2 exon 3. The break point in this case was not located in an Alu sequence. The 5'- and 3'-break point maps between the inverted Alu sequences in intron 2 and in exon 3, respectively, resulted in a 759-bp deletion. This novel exonic deletion in this PAH case may be a unique and non-recurrent rearrangement, and appears to be of a different size from that in other patients.Journal of Human Genetics advance online publication, 17 October 2013; doi:10.1038/jhg.2013.100.
    Journal of Human Genetics 10/2013; · 2.37 Impact Factor
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    ABSTRACT: The physiological mechanism of exercise-induced hyperpnea is an important and long-standing issue in respiratory physiology research.1 However, the precise mechanism of exercise-induced hyperpnea still is not understood. It has been confirmed that neural central command from the hypothalamus plays an important role in respiratory control during exercise.2 Activation of receptors in working muscle3,4 and stimulation of the carotid body by elevated plasma potassium5 have both been shown to contribute to exercise-induced hyperpnea. However, most of the other hypotheses to explain exercise-induced hyperpnea have been based on the observed close relationship between ventilation and the level of metabolic work; these hypotheses include (1) sensing of CO2 by receptors in the pulmonary circulation,6–9 (2) sensing of arterial CO2 partial pressure (PaCO2) as well as PaCO2 oscillation by the carotid body10,11 and (3) modulation of stretch-sensitive afferent activity by CO2.12,13 Thus, it has been widely assumed that metabolically produced CO2 is the most important element in the mechanism of exercise-induced hyperpnea. Therefore, the relationship between ventilation (Ve) and mixed venous CO2 partial pressure (PvCO2) as well as the relationship between Ve and PaCO2 needs to be fully analyzed in order to understand the contribution of metabolically produced CO2 to exercise-induced hyperpnea. However, most of the previous reports on PvCO2 dynamics during exercise in humans were not based on direct measurement, but rather on the estimation of PvCO2 by CO2 rebreathing,14,l5 and PvCO2 has been directly measured during exercise in humans only in a few studies.16 This is mainly because sampling of mixed venous blood during exercise in humans is technically difficult.
    10/2013;
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    ABSTRACT: OBJECTIVES: This study sought to identify useful predictors for hemodynamic improvement and risk of reperfusion pulmonary edema (RPE), a major complication of this procedure. BACKGROUND: Percutaneous transluminal pulmonary angioplasty (PTPA) has been reported to be effective for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). PTPA has not been widespread because RPE has not been well predicted. METHODS: We included 140 consecutive procedures in 54 patients with CTEPH. The flow appearance of the target vessels was graded into 4 groups (Pulmonary Flow Grade), and we proposed PEPSI (Pulmonary Edema Predictive Scoring Index) = (sum total change of Pulmonary Flow Grade scores) × (baseline pulmonary vascular resistance). Correlations between occurrence of RPE and 11 variables, including hemodynamic parameters, number of target vessels, and PEPSI, were analyzed. RESULTS: Hemodynamic parameters significantly improved after median observation period of 6.4 months, and the sum total changes in Pulmonary Flow Grade scores were significantly correlated with the improvement in hemodynamics. Multivariate analysis revealed that PEPSI was the strongest factor correlated with the occurrence of RPE (p < 0.0001). Receiver-operating characteristic curve analysis demonstrated PEPSI to be a useful marker of the risk of RPE (cutoff value 35.4, negative predictive value 92.3%). CONCLUSIONS: Pulmonary Flow Grade score is useful in determining therapeutic efficacy, and PEPSI is highly supportive to reduce the risk of RPE after PTPA. Using these 2 indexes, PTPA could become a safe and common therapeutic strategy for CTEPH.
    JACC. Cardiovascular Interventions 06/2013; · 1.07 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVE: Mutation of bone morphogenetic protein receptor type 2 (BMPR2) is a cause of pulmonary arterial hypertension (PAH). We measured the prevalence of this mutation and its impact on the phenotypes and long-term clinical outcomes in Japanese patients. METHODS: Between 1999 and 2007, we consecutively enrolled and, until March 2012, followed 49 Japanese patients with PAH, including 9 familial cases from 7 families. We genotyped BMPR2, using direct sequencing and multiplex ligation-dependent probe amplification, to examine a) the prevalence of BMPR2 mutations and gene rearrangement, b) the relationship between BMPR2 genotype and clinical phenotypes, and c) the long-term clinical outcomes of mutation carriers versus non-carriers under state-of-the-art medical therapy. RESULTS: BMPR2 mutations were present in 4 of the 7 families (57%) and in 14 of the 40 patients (35%) with sporadic PAH. The mean age at onset of PAH was 37.4 years in BMPR2 carriers, versus 25.9 years in non-carriers (P = 0.0025). The gender distribution and hemodynamic status at time of diagnosis were similar regardless of the mutation status. The 5-year survival rate after diagnosis of PAH was 88.5% in BMPR2 mutation carriers versus 80.9% in non-carriers (ns). CONCLUSIONS: The prevalence of BMPR2 mutations in Japanese with PAH was similar to that reported in other populations. At onset of PAH, BMPR2 mutation non-carriers were, on average, younger than carriers, possibly due to the heterogeneity of this subpopulation. With state-of-the-art therapy, the long-term survival of patients with PAH was high, regardless of the mutation status.
    Respirology 05/2013; · 2.78 Impact Factor
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    ABSTRACT: INTRODUCTION: Pulmonary arterial hypertension (PAH) is associated with poor prognosis despite significant recent advances in its treatment. An intravenous formulation of epoprostenol sodium containing glycine and mannitol (epoprostenol GM; GlaxoSmithKline, London, UK) is widely used to treat PAH. A new formulation of epoprostenol sodium containing arginine and sucrose excipients (epoprostenol AS; Actelion Pharmaceuticals Japan Ltd., Tokyo, Japan) shows better stability at room temperature after preparing diluted solutions. The primary objective of this study was to evaluate the safety and tolerability of switching from epoprostenol GM to epoprostenol AS in Japanese patients with PAH. The authors also evaluated the efficacy and treatment satisfaction after switching formulations. METHODS: This was a two-site, open-label, single-arm, Phase 3b study. Eight adult Japanese PAH patients (seven females) treated with a stable dose of epoprostenol GM for ≥30 days were switched to epoprostenol AS and followed for 12 weeks. Outcomes included safety, changes from baseline to 12 weeks in pulmonary hemodynamic factors (pulmonary vascular resistance, mean pulmonary arterial pressure, and cardiac output), and treatment satisfaction, assessed using the Treatment Satisfaction Questionnaire for Medication (TSQM-9). RESULTS: The mean (range) age and time since diagnosis of PAH were 48 (25-69) years and 6.2 (0.6-13.9) years, respectively. There were no unexpected safety or tolerability concerns after switching formulations. The epoprostenol dose was maintained after switching formulations. There were no significant changes in pulmonary hemodynamic factors from baseline to week 12. Regarding treatment satisfaction, there was a significant improvement in convenience, which is demonstrated in the score of the domain increased from 51.40 ± 10.19 at baseline to 58.33 ± 12.96 at week 12 (P < 0.05). CONCLUSIONS: Switching from epoprostenol GM to the same dose of epoprostenol AS was well tolerated over 12 weeks of treatment, and pulmonary hemodynamics were maintained. Switching to epoprostenol AS was also associated with improvements in treatment satisfaction (convenience). Clinical Trials: JapicCTI-122017.
    Advances in Therapy 05/2013; · 2.44 Impact Factor
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    ABSTRACT: Purpose:The purpose of this study was to undertake thorough genetic analysis of the bone morphogenetic protein type 2 receptor (BMPR2) gene in patients with pulmonary arterial hypertension.Methods:We conducted a systematic analysis for larger gene rearrangements together with conventional mutation analysis in 152 pulmonary arterial hypertension patients including 43 patients diagnosed as having idiopathic pulmonary arterial hypertension and 10 diagnosed as having familial pulmonary arterial hypertension.Results:Analysis of the BMPR2 gene revealed each of the four kinds of nonsense and frameshift mutations, one missense mutation, one splice-site mutation, and two types of exonic deletion. For cases in which exons 1-3 were deleted, the 5' and 3' break points were located in the AluY repeat sequences in the 5' side of the adjacent NOP58 gene and in the AluY repeat sequences in intron 3, suggesting an AluY-mediated nonallelic homologous recombination as the mechanism responsible for the deletion. For the case in which exon 10 was deleted, nonhomologous recombination took place between the AluSx site in intron 9 and a unique sequence in intron 10.Conclusion:Exonic deletions of BMPR2 account for at least part of BMPR2 mutations associated with heritable pulmonary arterial hypertension in Japan, as previously reported in other populations. One of our cases was mediated via Alu-mediated nonallelic homologous recombination and another was mediated via nonhomologous recombination.Genet Med advance online publication 11 April 2013Genetics in Medicine (2013); doi:10.1038/gim.2013.41.
    Genetics in medicine: official journal of the American College of Medical Genetics 04/2013; · 3.92 Impact Factor
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    ABSTRACT: OBJECTIVE: To assess the efficacy of epoprostenol treatment in Japanese patients with pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD). METHODS: Sixteen patients with PAH-CTD treated with continuous intravenous epoprostenol at a single center between 2000 and 2009 were enrolled. Baseline characteristics, short-term and long-term outcomes, predictors of mortality, and safety profiles were evaluated. For survival analysis, 16 controls were selected who matched the underlying CTD, World Health Organization functional class, and use of PAH drugs, except for epoprostenol. RESULTS: Six patients had systemic lupus erythematosus, five had mixed CTD, four had systemic sclerosis, and one had primary Sjögren's syndrome. The mean pulmonary arterial pressure (mPAP), cardiac index (CI), pulmonary vascular resistance, and functional class were significantly improved during the first 6 months of epoprostenol treatment. Cumulative survival rates at 1, 2, and 3 years in epoprostenol-treated patients were 69, 69, and 55 %, respectively, and were significantly better than those of the controls. Functional class, CI at baseline, and reduction of mPAP at 6 months were identified as predictors of survival. Adverse events, including flushing and catheter-related infection, were frequent, but all patients tolerated the treatment. CONCLUSION: Based on the improvements in both short-term and long-term outcomes among our patient cohort, epoprostenol is an effective treatment for CTD patients with advanced PAH.
    Modern Rheumatology 01/2013; · 1.72 Impact Factor
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    ABSTRACT: Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder caused by increased platelet destruction and impaired platelet production, induced by IgG anti-platelet autoantibodies [1]. Recently, we found that CD4(+) CD25(+) regulatory T-cell (Treg) depletion in mice causes the spontaneous development of sustained thrombocytopenia with increases in the platelet-associated IgG and the proportion of reticulated platelets [2]. Platelet eluates and the supernatants of splenocyte cultures prepared from these thrombocytopenic mice contained IgG antibodies capable of binding to intact platelets derived from normal mice, indicating that the primary mechanism was autoantibody-mediated, analogous to the pathophysiology of ITP. © 2012 International Society on Thrombosis and Haemostasis.
    Journal of Thrombosis and Haemostasis 11/2012; · 6.08 Impact Factor
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    ABSTRACT: BACKGROUND: CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION LEADS TO PULMONARY HYPERTENSION AND RIGHT-SIDED HEART FAILURE. THE PURPOSE OF THIS STUDY WAS TO INVESTIGATE THE EFFICACY OF PERCUTANEOUS TRANSLUMINAL PULMONARY ANGIOPLASTY (PTPA) FOR THE TREATMENT OF CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION.METHODS AND RESULTS: TWENTY-NINE PATIENTS WITH CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION UNDERWENT PTPA. ONE PATIENT HAD A WIRING PERFORATION AS A COMPLICATION OF PTPA AND DIED 2 DAYS AFTER THE PROCEDURE. IN THE REMAINING 28 PATIENTS, PTPA DID NOT PRODUCE IMMEDIATE HEMODYNAMIC IMPROVEMENT AT THE TIME OF THE PROCEDURE. HOWEVER, AFTER FOLLOW-UP (6.0 6.9 MONTHS), NEW YORK HEART ASSOCIATION FUNCTIONAL CLASSIFICATIONS AND LEVELS OF PLASMA B-TYPE NATRIURETIC PEPTIDE SIGNIFICANTLY IMPROVED (BOTH P0.01). HEMODYNAMIC PARAMETERS ALSO SIGNIFICANTLY IMPROVED (MEAN PULMONARY ARTERIAL PRESSURE, 45.3 9.8 VERSUS 31.8 10.0 MM HG; CARDIAC OUTPUT, 3.6 1.2 VERSUS 4.6 1.7 L/MIN, BASELINE VERSUS FOLLOW-UP, RESPECTIVELY; BOTH P0.01). TWENTY-SEVEN OF 51 PROCEDURES IN TOTAL (53%), AND 19 OF 28 FIRST PROCEDURES (68%), HAD REPERFUSION PULMONARY EDEMA AS THE CHIEF COMPLICATION. PATIENTS WITH SEVERE CLINICAL SIGNS AND/OR SEVERE HEMODYNAMICS AT BASELINE HAD A HIGH RISK OF REPERFUSION PULMONARY EDEMA.CONCLUSIONS: PTPA IMPROVED SUBJECTIVE SYMPTOMS AND OBJECTIVE VARIABLES, INCLUDING PULMONARY HEMODYNAMICS. PTPA MAY BE A PROMISING THERAPEUTIC STRATEGY FOR THE TREATMENT OF CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION.CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp. Unique identifier: UMIN000001572.
    Circulation Cardiovascular Interventions 11/2012; · 6.54 Impact Factor
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    ABSTRACT: The present study is the first report of the effectiveness of sorafenib in the treatment of pulmonary veno-occlusive disease (PVOD). A 66-year-old woman with PVOD was started on sorafenib. After 3 months of treatment with a maximum dosage of 400 mg/day sorafenib, there was an improvement in the patient's New York Heart Association (NYHA) functional class from IV to III. However, because of severe painful eruptions as a side effect of sorafenib, the patient stopped sorafenib and was started on imatinib instead. This treatment resulted in a worsening of the patient's NYHA class from III to IV, so sorafenib was restarted at a reduced dosage of 300 mg/day. The resumption of sorafenib was associated with clinical improvement, specifically NYHA class from IV to II and hemodynamic amelioration, and tolerable eruptions. In conclusion, sorafenib may be a potential therapeutic strategy for the treatment of PVOD.
    Cardiology 10/2012; 123(3):172-174. · 1.52 Impact Factor
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    ABSTRACT: Prostaglandin I(2) (PGI(2)) plays an important role in the clinical treatment of pulmonary arterial hypertension (PAH). However, the administration of PGI(2) involves continuous intravenous infusion using an indwelling catheter, which limits the patient's quality of life and increases the risk of infection. We therefore investigated whether human PGI(2) synthase (hPGIS) gene transfer using an adeno-associated virus (AAV) vector is still effective in a mouse model of PAH and tested for differences in the therapeutic efficacy of PAH among AAV serotypes. The PAH was induced by subjecting mice to hypoxia (10% O(2)). Type 1 AAV expressing hPGIS (AAV1-hPGIS) or type 2 AAV expressing hPGIS (AAV2-hPGIS) was injected into the thigh muscle of mice. Both vectors expressing hPGIS produced strong hPGIS protein expression in the mouse thigh skeletal muscles after 8 weeks of hypoxia. The administration of AAV1-hPGIS or AAV2-hPGIS also significantly inhibited the hypoxia-induced increase in right ventricular systolic pressure, the ratio of right ventricular weight to body weight (RV/BW), and the ratio of RV weight to left ventricular plus septal weight (RV/LV + S), and significantly attenuated the hypoxia-induced increase in medial wall thickness of peripheral pulmonary arteries. Furthermore, there were no significant differences in the degree of amelioration in RV systolic pressure, RV/BW, RV/LV + S, and percentage of wall thickness of peripheral pulmonary arteries between AAV1-hPGIS and AAV2-hPGIS administrations. In conclusion, we revealed that type 1 and type 2 AAV are equally effective for the treatment of PAH in a hypoxia-induced mouse model. Gene-transfer therapy using AAV expressing hPGIS is, therefore, a potential therapeutic breakthrough for PAH.
    Journal of Cardiovascular Pharmacology and Therapeutics 09/2012; · 3.07 Impact Factor
  • American Journal of Respiratory and Critical Care Medicine 08/2012; 186(3):291-2. · 11.04 Impact Factor
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    ABSTRACT: Antibodies against double-stranded DNA (dsDNA) are widely used to diagnose systemic lupus erythematosus (SLE) and evaluate its activity in patients. This study was undertaken to examine the clinical utility of circulating anti-dsDNA antibody-secreting cells for evaluating SLE patients. Anti-dsDNA antibody-secreting cells quantified using an enzyme-linked immunospot assay were detected in the spleen, bone marrow and peripheral blood from MRL/lpr but not in control BALB/c mice. Circulating anti-dsDNA antibody-secreting cells were detected in 29 (22%) of 130 patients with SLE, but in none of 49 with non-SLE connective-tissue disease or 18 healthy controls. The presence of circulating anti-dsDNA antibody-secreting cells was associated with persistent proteinuria, high SLE disease activity index and systemic lupus activity measures, and a high serum anti-dsDNA antibody titre measured with an enzyme-linked immunosorbent assay. The positive predictive value for active disease was 48% for circulating anti-dsDNA antibody-secreting cells versus 17% for serum anti-dsDNA antibodies. A prospective cohort of patients with circulating anti-dsDNA antibodies and inactive SLE showed that the cumulative disease flare-free rate was significantly lower in patients with than without circulating anti-dsDNA antibody-secreting cells (p < 0.001). Circulating anti-dsDNA antibody-secreting cells are a useful biomarker for assessing disease activity in SLE patients.
    Lupus 06/2012; 21(12):1284-93. · 2.78 Impact Factor

Publication Stats

3k Citations
497.79 Total Impact Points

Institutions

  • 2011–2014
    • Kyorin University
      • School of Medicine
      Edo, Tōkyō, Japan
  • 1997–2013
    • Keio University
      • • Department of Internal Medicine
      • • Department of Cardiology
      • • School of Medicine
      Tokyo, Tokyo-to, Japan
  • 1997–2006
    • National Cerebral and Cardiovascular Center
      • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan