研究者詳細 - 三好　亨

論文 - 三好　亨

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Prognostic Value of Coronary Computed Tomographic Angiography in Patients With Nonalcoholic Fatty Liver Disease 査読

Ichikawa K, Miyoshi T, Osawa K, Miki T, Nakamura K, Ito H

JACC Cardiovasc Imaging 13 ( 7 ) 1628 - 1630 2020年7月

Prognostic Value of Coronary Computed Tomographic Angiography in Patients With Nonalcoholic Fatty Liver Disease. 国際誌

Keishi Ichikawa, Toru Miyoshi, Kazuhiro Osawa, Takashi Miki, Kazufumi Nakamura, Hiroshi Ito

JACC. Cardiovascular imaging 13 ( 7 ) 1628 - 1630 2020年7月

【臨床医が知っていほしい循環器基礎研究最新の成果】心不全　酸化ストレスは心不全の原因か?

中村一文、網岡尚史、三好　亨、伊藤　浩

循環器内科 87 ( 5 ) 597 - 600 2020年5月

Automated interpretation of the coronary angioscopy with deep convolutional neural networks. 国際誌

Toru Miyoshi, Akinori Higaki, Hideo Kawakami, Osamu Yamaguchi

Open heart 7 ( 1 ) 2020年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Coronary angioscopy (CAS) is a useful modality to assess atherosclerotic changes, but interpretation of the images requires expert knowledge. Deep convolutional neural networks (DCNN) can be used for diagnostic prediction and image synthesis. METHODS: 107 images from 47 patients, who underwent CAS in our hospital between 2014 and 2017, and 864 images, selected from 142 MEDLINE-indexed articles published between 2000 and 2019, were analysed. First, we developed a prediction model for the angioscopic findings. Next, we made a generative adversarial networks (GAN) model to simulate the CAS images. Finally, we tried to control the output images according to the angioscopic findings with conditional GAN architecture. RESULTS: For both yellow colour (YC) grade and neointimal coverage (NC) grade, we could observe strong correlations between the true grades and the predicted values (YC grade, average r=0.80±0.02, p<0.001; NC grade, average r=0.73±0.02, p<0.001). The binary classification model for the red thrombus yielded 0.71±0.03 F1-score and the area under the receiver operator characteristic curve was 0.91±0.02. The standard GAN model could generate realistic CAS images (average Inception score=3.57±0.06). GAN-based data augmentation improved the performance of the prediction models. In the conditional GAN model, there were significant correlations between given values and the expert's diagnosis in YC grade but not in NC grade. CONCLUSION: DCNN is useful in both predictive and generative modelling that can help develop the diagnostic support system for CAS.

DOI： 10.1136/openhrt-2019-001177

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Deficiency of CD44 prevents thoracic aortic dissection in a murine model 査読

Hatipoglu OF, Miyoshi T, Yonezawa T, Kondo M, Amioka N, Yoshida M, Akagi S, Nakamura K, Hirohata S, Ito H

Sci Rep 10 ( 1 ) 6869 2020年4月

Deficiency of CD44 prevents thoracic aortic dissection in a murine model. 国際誌

Omer F Hatipoglu, Toru Miyoshi, Tomoko Yonezawa, Megumi Kondo, Naofumi Amioka, Masashi Yoshida, Satoshi Akagi, Kazufumi Nakamura, Satoshi Hirohata, Hiroshi Ito

Scientific reports 10 ( 1 ) 6869 - 6869 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Thoracic aortic dissection (TAD) is a life-threatening vascular disease. We showed that CD44, a widely distributed cell surface adhesion molecule, has an important role in inflammation. In this study, we examined the role of CD44 in the development of TAD. TAD was induced by the continuous infusion of β-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, and angiotensin II (AngII) for 7 days in wild type (WT) mice and CD44 deficient (CD44-/-) mice. The incidence of TAD in CD44-/- mice was significantly reduced compared with WT mice (44% and 6%, p < 0.01). Next, to evaluate the initial changes, aortic tissues at 24 hours after BAPN/AngII infusion were examined. Neutrophil accumulation into thoracic aortic adventitia in CD44-/- mice was significantly decreased compared with that in WT mice (5.7 ± 0.3% and 1.6 ± 0.4%, p < 0.01). In addition, BAPN/AngII induced interleukin-6, interleukin-1β, matrix metalloproteinase-2 and matrix metalloproteinase-9 in WT mice, all of which were significantly reduced in CD44-/- mice (all p < 0.01). In vitro transmigration of neutrophils from CD44-/- mice through an endothelial monolayer was significantly decreased by 18% compared with WT mice (p < 0.01). Our findings indicate that CD44 has a critical role in TAD development in association with neutrophil infiltration into adventitia.

DOI： 10.1038/s41598-020-63824-9

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Clinical Utility of Diffusion-weighted Whole-body Magnetic Resonance Imaging with Background Body Signal Suppression for Assessing and Monitoring IgG4-related Disease.

Akira Oshita, Yusuke Kono, Toru Miyoshi, Moeko Suzuki, Takuro Kazatani, Hiroshi Matsuoka, Hideo Kawakami

Internal medicine (Tokyo, Japan) 59 ( 7 ) 951 - 955 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 77-year-old man with symptoms of chest pain was diagnosed with immunoglobulin G4 (IgG4)-related disease. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) revealed an intense uptake in the submandibular gland, lymph nodes and abdominal aortic wall. Diffusion-weighted imaging with background body signal suppression (DWIBS) revealed signal enhancements at the same location as those of the FDG-PET/CT findings. The DWIBS signal intensity decreased after steroid treatment, so we decreased the steroid dosage. Relapse did not occur. DWIBS makes it possible to adjust the medicine dosage while confirming the therapeutic effects and will likely be a useful method for monitoring IgG4-related disease.

DOI： 10.2169/internalmedicine.3712-19

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Effects of Bisoprolol Transdermal Patches for Prevention of Perioperative Myocardial Injury in High-Risk Patients Undergoing Non-Cardiac Surgery　- Multicenter Randomized Controlled Study 査読

Toda H, Nakamura K, Shimizu K, Ejiri K, Iwano T, Miyoshi T, Nakagawa K, Yoshida M, Watanabe A, Nishii N, Hikasa Y, Hayashi M, Morita H, Morimatsu H, Ito H; MAMACARI Investigators

Circ J 84 ( 4 ) 642 - 649 2020年3月

Effects of Bisoprolol Transdermal Patches for Prevention of Perioperative Myocardial Injury in High-Risk Patients Undergoing Non-Cardiac Surgery - Multicenter Randomized Controlled Study.

Hironobu Toda, Kazufumi Nakamura, Kazuyoshi Shimizu, Kentaro Ejiri, Takayuki Iwano, Toru Miyoshi, Koji Nakagawa, Masashi Yoshida, Atsuyuki Watanabe, Nobuhiro Nishii, Yukiko Hikasa, Masao Hayashi, Hiroshi Morita, Hiroshi Morimatsu, Hiroshi Ito

Circulation journal : official journal of the Japanese Circulation Society 84 ( 4 ) 642 - 649 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of transdermal β-blocker patches, which offer stable blood concentration and easy availability during operation, for prevention of perioperative myocardial injury (PMI) in high-risk patients.Methods and Results:In this randomized controlled trial, patients aged >60 years with hypertension and high revised cardiac risk index (≥2) undergoing non-cardiac surgery were randomly assigned to a bisoprolol patch or control group. Primary efficacy outcome was incidence of PMI, defined as postoperative high-sensitivity cardiac troponin T (hs-cTnT) >0.014ng/mL and relative hs-cTnT change ≥20%. Secondary efficacy outcomes were number of cardiovascular events and 30-day mortality. From November 2014 to February 2019, 240 patients from 5 hospitals were enrolled in this study. The incidence of PMI was 35.7% in the bisoprolol patch group and 44.5% in the control group (P=0.18). Incidence of major adverse cardiac events including non-critical myocardial infarction, strokes, decompensated heart failure and tachyarrhythmia was similar between the 2 groups. Tachyarrhythmia tended to be higher in the control group. There were no significant differences in safety outcomes including significant hypotension and bradycardia requiring any treatment between the 2 groups. CONCLUSIONS: Bisoprolol patches do not influence the incidence of PMI and cardiovascular events in high-risk patients undergoing non-cardiac surgery, but perioperative use of these patches is safe.

DOI： 10.1253/circj.CJ-19-0871

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New Appearance of Fragmented QRS as a Predictor of Ventricular Arrhythmic Events in Patients With Hypertrophic Cardiomyopathy 査読

Ogura S, Nakamura K, Morita H, Toh N, Nakagawa K, Yoshida M, Watanabe A, Nishii N, Miyoshi T, Ito H

Circ J 84 ( 3 ) 487 - 494 2020年2月

New Appearance of Fragmented QRS as a Predictor of Ventricular Arrhythmic Events in Patients With Hypertrophic Cardiomyopathy.

Soichiro Ogura, Kazufumi Nakamura, Hiroshi Morita, Norihisa Toh, Koji Nakagawa, Masashi Yoshida, Atsuyuki Watanabe, Nobuhiro Nishii, Toru Miyoshi, Hiroshi Ito

Circulation journal : official journal of the Japanese Circulation Society 84 ( 3 ) 487 - 494 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Multiple spikes in the QRS complex (fragmented QRS [fQRS]) on 12-lead electrocardiography have been associated with ventricular arrhythmic events (VAEs) in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to assess the association between new appearances of fQRS and cardiac events in patients with HCM.Methods and Results:The association between baseline fQRS and cardiac events, namely VAEs, heart failure-related hospitalization, and all-cause death, was evaluated retrospectively in 146 HCM patients (46 patients with fQRS, 100 without fQRS). The median follow-up was 5.3 years. Cardiac events occurred in 29 patients with baseline fQRS and 32 patients without baseline fQRS (63% vs. 32%; P<0.001). VAEs occurred in a significantly larger percentage of patients with than without baseline fQRS (54% vs. 23%, respectively; P<0.001). Of the 100 patients without baseline fQRS, 33 had a new appearance of fQRS during the 4.6-year follow-up, whereas 67 did not. VAEs occurred more frequently in the 33 patients with the appearance of fQRS than in those without (42% vs. 13%, respectively; P=0.001). Multivariable analysis showed that the new appearance of fQRS documented before VAEs was associated with VAEs (hazard ratio 4.29, 95% confidence interval 1.81-10.2; P=0.001). CONCLUSIONS: The new appearance of fQRS was associated with an increased risk of VAEs in HCM patients.

DOI： 10.1253/circj.CJ-19-0968

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大動脈疾患の最新トピックス　接着分子CD44の機能制御と大動脈瘤・大動脈解離における役割

Hatipoglu Omer F., 三好　亨

血管 43 ( 1 ) 28 2020年1月

Pathology of Coronary Artery Embolism Derived From Mural Thrombus of Left Ventricle.

Toru Miyoshi, Hiroyuki Hao, Akira Oshita, Hideo Kawakami, Toshiharu Maeda, Hiroshi Matsuoka

Circulation journal : official journal of the Japanese Circulation Society 84 ( 1 ) 129 - 129 2019年12月

Low Consultation Rate of General Population with Atrial Fibrillation.

Hiroaki Matsumi, Kazufumi Nakamura, Eri Eguchi, Toru Miyoshi, Koji Nakagawa, Nobuhiro Nishii, Atsuyuki Watanabe, Akira Ueoka, Masashi Yoshida, Naoto Tokunaga, Naofumi Amioka, Nobuyuki Yamada, Daiji Saito, Hiroshi Morita, Keiki Ogino, Hiroshi Ito

International heart journal 60 ( 6 ) 1303 - 1307 2019年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

In order to prevent ischemic stroke, it is important to identify and treat patients with atrial fibrillation (AF) who do not consult a doctor in a medical institution. The aim of this study was to determine the consultation rate at medical institutions for patients with AF in group medical examinations conducted in a city in western Japan. Of 6101 examinees of group medical examinations (40 years of age or older) conducted in Ibara City, Okayama Prefecture, Japan, from 2012 to 2014, 4338 participants (71.1%) who were evaluated by electrocardiogram (ECG) gave written informed consent and responded to surveys in the form of questionnaires through a personal interview conducted by nurses were included in the Ibara-AF study. A cumulative total of 82 subjects were diagnosed as having AF by ECG (prevalence of AF = 1.89%), and 51 individuals had AF during the three-year period.15 (29.4%) of the 51 patients with AF did not regularly visit medical institutions. Among them, 46.7% (n = 7) and 53.3% (n = 8) of the patients were symptomatic and asymptomatic, respectively, and 73.3% of the patients had a CHADS2 score of more than one point. There were no significant differences in patients' characteristics between regular and non-regular visit groups. In conclusion, about one-third of the patients with AF did not regularly see a doctor in a medical institution and most of them had a CHADS2 score of more than one point in a Japanese rural area. Educating the public about the risks of AF is required.

DOI： 10.1536/ihj.19-062

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Current Treatment Strategies and Nanoparticle-Mediated Drug Delivery Systems for Pulmonary Arterial Hypertension. 国際誌

Kazufumi Nakamura, Satoshi Akagi, Kentaro Ejiri, Masashi Yoshida, Toru Miyoshi, Norihisa Toh, Koji Nakagawa, Yoichi Takaya, Hiromi Matsubara, Hiroshi Ito

International journal of molecular sciences 20 ( 23 ) 2019年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

There are three critical pathways for the pathogenesis and progression of pulmonary arterial hypertension (PAH): the prostacyclin (prostaglandin I2) (PGI2), nitric oxide (NO), and endothelin pathways. The current approved drugs targeting these three pathways, including prostacyclin (PGI2), phosphodiesterase type-5 (PDE5) inhibitors, and endothelin receptor antagonists (ERAs), have been shown to be effective, however, PAH remains a severe clinical condition and the long-term survival of patients with PAH is still suboptimal. The full therapeutic abilities of available drugs are reduced by medication, patient non-compliance, and side effects. Nanoparticles are expected to address these problems by providing a novel drug delivery approach for the treatment of PAH. Drug-loaded nanoparticles for local delivery can optimize the efficacy and minimize the adverse effects of drugs. Prostacyclin (PGI2) analogue, PDE5 inhibitors, ERA, pitavastatin, imatinib, rapamycin, fasudil, and oligonucleotides-loaded nanoparticles have been reported to be effective in animal PAH models and in vitro studies. However, the efficacy and safety of nanoparticle mediated-drug delivery systems for PAH treatment in humans are unknown and further clinical studies are required to clarify these points.

DOI： 10.3390/ijms20235885

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Serum malondialdehyde-modified low-density lipoprotein levels on admission predict prognosis in patients with acute coronary syndrome undergoing percutaneous coronary intervention. 国際誌

Naofumi Amioka, Toru Miyoshi, Hiroaki Otsuka, Daisuke Yamada, Atsushi Takaishi, Masayuki Ueeda, Satoshi Hirohata, Hiroshi Ito

Journal of cardiology 74 ( 3 ) 258 - 266 2019年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) is a predictive marker of cardiovascular events in patients with stable angina pectoris. However, little is known about this marker in patients with acute coronary syndrome (ACS). We investigated the prognostic relevance of MDA-LDL to cardiovascular outcomes in patients with ACS. METHODS: A total of 370 consecutive patients with ACS who underwent primary percutaneous coronary intervention (PCI) were enrolled from October 2009 to September 2014 at Mitoyo General Hospital. Serum MDA-LDL levels were measured at admission. The patients were divided into three tertile groups according to serum MDA-LDL levels. The primary outcomes were cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, revascularization, and heart failure requiring hospital admission. RESULTS: MDA-LDL levels in patients with acute myocardial infarction were significantly greater than those in patients with unstable angina pectoris (mean±standard deviation: 133±48U/L vs. 157±69U/L, p=0.001). During follow-up [472 (195-920) days], 82 (22%) events occurred. Kaplan-Meier analysis showed that patients in the highest MDA-LDL tertile had the worst prognosis (log-rank, p<0.001). Cox regression analysis showed that serum MDA-LDL levels were an independent predictor of cardiovascular events after PCI in patients with ACS, even after adjustment for age, sex, body mass index, conventional cardiovascular risk factors, other lipid biomarkers, statin use on admission, cardiac biomarkers, and presence or absence of multivessel disease (hazard ratio: 1.80 per 1 standard deviation U/L increase, 95% confidence interval: 1.07-3.16, p=0.027). CONCLUSION: Serum MDA-LDL levels on admission are a significant prognostic marker in patients with ACS who undergo successful PCI.

DOI： 10.1016/j.jjcc.2019.02.012

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Brachial intima-media thickness is associated with coronary artery atherosclerosis in patients with diabetes mellitus.

Tamaki Ono, Toru Miyoshi, Yuko Ohno, Kazuhiro Osawa, Yoichi Takaya, Takashi Miki, Keishi Ichikawa, Hiroshi Ito

Heart and vessels 34 ( 9 ) 1405 - 1411 2019年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Coronary artery calcification (CAC) as measured by computed tomography is a strong predictor of coronary artery disease. The brachial intima-media thickness (IMT) was recently reported to be associated with cardiovascular risk factors. This study investigated the association of brachial IMT with CAC, which is a marker of coronary artery atherosclerosis, in patients with diabetes. We enrolled 292 patients with diabetes (mean age, 65 ± 12 years; 59% men) who underwent both endothelial function testing and computed tomography for risk assessment of coronary artery disease. Flow-mediated dilation (FMD) and IMT in the brachial artery were measured with a specialized machine. FMD was lower and brachial IMT was thicker in patients with than without CAC. The CAC score was significantly correlated with both brachial IMT and FMD, while the multivariate logistic analysis demonstrated that brachial IMT (> 0.32 mm) but not FMD (< 5.1%) was significantly associated with the presence of CAC (odds ratio, 2.03; 95% confidence interval, 1.10-3.77; p = 0.02). The receiver operating characteristic curve analysis showed that the area under the curve for discriminating patients with CAC was 0.67 for IMT (p < 0.001) and 0.62 for FMD (p < 0.001). When patients were classified into four groups based on brachial IMT and FMD, the CAC score was higher in patients with thicker brachial IMT and lower FMD than in patients of the other groups (p < 0.001). Measurement of brachial IMT could be useful for the risk assessment of patients with diabetes.

DOI： 10.1007/s00380-019-01371-8

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遺残坐骨動脈瘤に対しステントグラフト(VIABAHN)を用いて治療した一例査読

大塚寛昭, 戸田洋伸, 江尻健太郎, 杜徳尚, 三好亨, 中村一文, 伊藤浩

日本心血管インターベンション治療学会抄録集 28回 [MP34 - 006] 2019年9月

Prognostic Value and Risk Continuum of Noninvasive Fractional Flow Reserve Derived from Coronary CT Angiography. 国際誌

Abdul Rahman Ihdayhid, Bjarne L Norgaard, Sara Gaur, Jonathan Leipsic, Nitesh Nerlekar, Kazuhiro Osawa, Toru Miyoshi, Jesper M Jensen, Takeshi Kimura, Hiroki Shiomi, Andrejs Erglis, Sanda Jegere, Keith G Oldroyd, Hans Erik Botker, Sujith K Seneviratne, Stephan Achenbach, Brian S Ko

Radiology 292 ( 2 ) 343 - 351 2019年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background Coronary CT angiography with noninvasive fractional flow reserve (FFR) predicts lesion-specific ischemia when compared with invasive FFR. The longer term prognostic value of CT-derived FFR (FFRCT) is unknown. Purpose To determine the prognostic value of FFRCT when compared with coronary CT angiography and describe the relationship of the numeric value of FFRCT with outcomes. Materials and Methods This prospective subanalysis of the NXT study (Clinicaltrials.gov: NCT01757678) evaluated participants suspected of having stable coronary artery disease who were referred for invasive angiography and who underwent FFR, coronary CT angiography, and FFRCT. The incidence of the composite primary end point of death, myocardial infarction, and any revascularization and the composite secondary end point of major adverse cardiac events (MACE: cardiac death, myocardial infarction, unplanned revascularization) were compared for an FFRCT of 0.8 or less versus stenosis of 50% or greater on coronary CT angiograms, with treating physicians blinded to the FFRCT result. Results Long-term outcomes were obtained in 206 individuals (age, 64 years ± 9.5), including 64% men. At median follow-up of 4.7 years, there were no cardiac deaths or myocardial infarctions in participants with normal FFRCT. The incidence of the primary end point was more frequent in participants with positive FFRCT compared with clinically significant stenosis at coronary CT angiography (73.4% [80 of 109] vs 48.7% [91 of 187], respectively; P < .001), with the majority of outcomes being planned revascularization. Corresponding hazard ratios (HRs) were 9.2 (95% confidence interval [CI]: 5.1, 17; P < .001) for FFRCT and 5.9 (95% CI: 1.5, 24; P = .01) for coronary CT angiography. FFRCT was a superior predictor compared with coronary CT angiography for primary end point (C-index FFRCT, 0.76 vs coronary CT angiography, 0.54; P < .001) and MACE (FFRCT, 0.71 vs coronary CT angiography, 0.52; P = .001). Frequency of MACE was higher in participants with positive FFRCT compared with coronary CT angiography (15.6% [17 of 109] vs 10.2% [19 of 187], respectively; P = .02), driven by unplanned revascularization. MACE HR was 5.5 (95% CI: 1.6, 19; P = .006) for FFRCT and 2.0 (95% CI: 0.3, 14; P = .46) for coronary CT angiography. Each 0.05-unit FFRCT reduction was independently associated with greater incidence of primary end point (HR, 1.7; 95% CI: 1.4, 1.9; P < .001) and MACE (HR, 1.4; 95% CI: 1.1, 1.8; P < .001). Conclusion In stable patients referred for invasive angiography, a CT-derived fractional flow reserve (FFRCT) value of 0.8 or less was a predictor of long-term outcomes driven by planned and unplanned revascularization and was superior to clinically significant stenosis on coronary CT angiograms. Additionally, the numeric value of FFRCT was an independent predictor of outcomes. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Dennie and Rubens in this issue.

DOI： 10.1148/radiol.2019182264

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Combination of Renal Angioplasty and Angiotensin-converting-enzyme Inhibitor Can Reduce Proteinuria in Patients with Bilateral Renal Artery Disease.

Hironobu Toda, Haruhito Uchida, Kazufumi Nakamura, Hidemi Takeuchi, Masaru Kinomura, Koji Nakagawa, Atsuyuki Watanabe, Toru Miyoshi, Nobuhiro Nishii, Hiroshi Morita, Jun Wada, Hiroshi Ito

Internal medicine (Tokyo, Japan) 58 ( 13 ) 1917 - 1922 2019年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Recent large clinical trials failed to show clear benefits of percutaneous transluminal renal angioplasty (PTRA) as compared with medical therapy on patients with renal artery stenosis. It was also reported that proteinuria is an adverse prognostic factor after PTRA, and PTRA is less effective in patients with overt proteinuria. From the renoprotective point of view, to reduce proteinuria after PTRA is an important therapeutic goal in patients with renal artery stenosis with overt proteinuria. We hereby describe two patients successfully treated by combination therapy with PTRA and administration of angiotensin-converting enzyme (ACE) inhibitor for bilateral renal artery disease with overt proteinuria.

DOI： 10.2169/internalmedicine.2076-18

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