Faculty Profiles - MIYOSHI Toru

Papers - MIYOSHI Toru

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Cardio-Ankle Vascular Index as an Arterial Stiffness Marker Improves the Prediction of Cardiovascular Events in Patients without Cardiovascular Diseases. International journal

Yuko Okamoto, Toru Miyoshi, Keishi Ichikawa, Yoichi Takaya, Kazufumi Nakamura, Hiroshi Ito

Journal of cardiovascular development and disease 9 ( 11 ) 2022.10

Language：English Publishing type：Research paper (scientific journal)

Several studies have reported that the cardio-ankle vascular index (CAVI), a non-invasive measurement of arterial stiffness, is associated with the incidence of cardiovascular events. We investigated whether adding CAVI to a risk score improves the prediction of cardiovascular events in the setting of primary prevention. This retrospective observational study included consecutive 554 outpatients with cardiovascular disease risk factors but without known cardiovascular disease (68 ± 9 years, 64% men). The CAVI was measured using the VaSera vascular screening system. Major adverse cardiovascular events (MACE) included cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization. During a median follow-up of 4.3 years, cardiovascular events occurred in 65 patients (11.7%). Multivariate Cox analysis showed that abnormal CAVI (>9.0) was significantly associated with the incidence of MACE (hazard ratio 2.31, 95% confidence interval 1.27−4.18). The addition of CAVI to the Suita score, a conventional risk score for coronary heart disease in Japan, significantly improved the C statics from 0.642 to 0.713 (p = 0.04). In addition to a conventional risk score, CAVI improved the prediction of cardiovascular events in patients with cardiovascular disease risk factors but without known cardiovascular diseases.

DOI： 10.3390/jcdd9110368

The Fibrosis-4 Index Predicts Cardiovascular Prognosis in Patients With Severe Isolated Tricuspid Regurgitation.

Mitsutaka Nakashima, Machiko Tanakaya, Toru Miyoshi, Takaaki Saito, Yusuke Katayama, Satoru Sakuragi, Hiroshi Ito

Circulation journal : official journal of the Japanese Circulation Society 86 ( 11 ) 1777 - 1784 2022.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The fibrosis-4 (FIB-4) index is used to evaluate liver disease patients. It can also be used to evaluate the prognosis for heart disease patients; however, its ability to determine the prognosis of severe isolated tricuspid regurgitation (TR) patients is unclear. This study aimed to clarify the association between FIB-4 index scores and the cardiovascular prognosis for severe isolated TR patients.Methods and Results: This was a dual-center, retrospective study. From 2011 to 2019, 111 consecutive outpatients with severe isolated TR (mean age, 68.6 years; 53.2% male) were evaluated. Major adverse cardiovascular events (MACEs) were defined as the composite of cardiovascular death, hospitalization for heart failure, myocardial infarction, and stroke. The association between FIB-4 index scores and echocardiography was also evaluated. During a median follow up of 3.0 years, 24 patients were lost to follow up and 40 MACEs occurred. Baseline FIB-4 index scores for patients with MACEs were significantly higher than those for patients without MACEs. A multivariate analysis revealed that FIB-4 index scores are significantly associated with MACEs (hazard ratio, 1.89; 95% confidence interval, 1.01-3.54; P=0.046). A linear regression analysis indicated that FIB-4 index scores were correlated with echocardiographic parameters, including the left atrial volume index and left ventricular end-diastolic diameter. CONCLUSIONS: The FIB-4 index score may be a useful predictor of MACEs for patients with severe isolated TR.

DOI： 10.1253/circj.CJ-22-0109

The Association of Triglyceride to High-Density Lipoprotein Cholesterol Ratio with High-Risk Coronary Plaque Characteristics Determined by CT Angiography and Its Risk of Coronary Heart Disease. International journal

Yuji Koide, Toru Miyoshi, Takahiro Nishihara, Mitsutaka Nakashima, Keishi Ichikawa, Takashi Miki, Kazuhiro Osawa, Hiroshi Ito

Journal of cardiovascular development and disease 9 ( 10 ) 2022.9

Language：English Publishing type：Research paper (scientific journal)

The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is an independent risk index for cardiovascular events. This study aimed to evaluate the association between TG/HDL-C ratio and coronary plaque characteristics as seen on coronary computed tomography angiography (CCTA) and the corresponding increase in the likelihood of cardiovascular events. A total of 935 patients who underwent CCTA for suspected coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined based on three characteristics: positive remodeling, low-density plaques, and spotty calcification. Significant stenosis was defined as luminal narrowing of >70%. Patients with a higher TG/HDL-C ratio showed significantly greater prevalence of HRP and significant stenosis than patients with low TG/HDL-C ratios (p < 0.01). Multivariate logistic analysis demonstrated that the TG/HDL-C ratio was significantly associated with the presence of HRP (p < 0.01) but not with significant coronary stenosis (p = 0.24). During the median follow-up period of 4.1 years, 26 cardiovascular events including cardiovascular death and acute coronary syndrome occurred. The highest TG/HDL-C tertile was associated with cardiovascular events, with the lowest TG/HDL-C tertile as the reference (hazard ratio, 3.75; 95% confidence interval, 1.04−13.50). A high TG/HDL-C ratio is associated with the presence of CCTA-verified HRP, which can lead to cardiovascular events in patients with suspected CAD.

DOI： 10.3390/jcdd9100329

Effects of luseogliflozin and voglibose on high-risk lipid profiles and inflammatory markers in diabetes patients with heart failure. International journal

Kentaro Ejiri, Toru Miyoshi, Hajime Kihara, Yoshiki Hata, Toshihiko Nagano, Atsushi Takaishi, Hironobu Toda, Seiji Namba, Yoichi Nakamura, Satoshi Akagi, Satoru Sakuragi, Taro Minagawa, Yusuke Kawai, Nobuhiro Nishii, Soichiro Fuke, Masaki Yoshikawa, Kazufumi Nakamura, Hiroshi Ito

Scientific reports 12 ( 1 ) 15449 - 15449 2022.9

Language：English Publishing type：Research paper (scientific journal)

Sodium-glucose cotransporter 2 inhibitors could reduce cardiovascular events in patients with heart failure irrespective of diabetes status. In this prespecified sub-analysis of randomised-controlled trial, we investigated the efficacy of luseogliflozin (2.5 mg daily), a sodium-glucose cotransporter 2 inhibitor, with that of voglibose (0.6 mg daily), an alpha-glucosidase inhibitor, on high-risk lipid profile and inflammatory markers in patients with type-2 diabetes and heart failure. Among the 157 patients studied, there were no significant differences in the mean malondialdehyde LDL or small-dense LDL cholesterol levels between the luseogliflozin and voglibose groups (percent change: 0.2% vs. - 0.6%, p = 0.93; - 1.7% vs. - 8.6%, p = 0.21) after 12 weeks in comparison to levels at the baseline. No significant difference was observed between the two groups in the adiponectin and high-sensitivity C-reactive protein levels after 12 weeks compared to the baseline levels (percent change, - 1.6% vs. - 4.0% and 22.5% vs. 10.0%; p = 0.52 and p = 0.55, respectively). In conclusion, in patients with type-2 diabetes and heart failure, compared to voglibose, luseogliflozin did not significantly improve the high-risk lipoprotein profile including malondialdehyde LDL and small-dense LDL cholesterol or the levels of inflammatory markers, including adiponectin and high-sensitivity C-reactive protein.Trial registration: Trial number: UMIN-CTR, UMIN000018395; Registered 23 July 2015; URL: https://www.umin.ac.jp/ctr/index.htm .

DOI： 10.1038/s41598-022-19371-6

High platelet reactivity is a predictor of left ventricular remodelling in patients with acute myocardial infarction

Masahiro Tsuji, Yusuke Kawai, Toru Miyoshi, Eisuke Saito, Kohei Kawamura, Tamaki Ono, Koji Tokioka, Tohru Ohe, Kazufumi Nakamura, Hiroshi Ito

ESC Heart Failure 9 ( 5 ) 3565 - 3574 2022.7

Publishing type：Research paper (scientific journal) Publisher：Wiley

Abstract

Aims

Acute myocardial infarction (AMI) is associated with left ventricular remodelling (LVR), which leads to progressive heart failure. Platelets play a pivotal role in promoting systemic and cardiac inflammatory responses during the complex process of myocardial wound healing or repair following AMI. This study aimed to investigate the impact of platelet reactivity immediately after primary percutaneous coronary intervention (PCI) on LVR in AMI patients with ST‐segment (STEMI) and non‐ST‐segment elevation (NSTEMI).

Methods and results

This prospective, single‐centre, observational study included 182 patients with AMI who underwent primary PCI (107 patient with STEMI and 75 patients with NSTEMI). Patients were administered a loading dose of aspirin plus prasugrel before the procedure, and platelet reactivity was assessed using the VerifyNow P2Y12 assay immediately after PCI. Echocardiography was performed before discharge and during the chronic phase (8 ± 3 months after discharge). LVR was defined as a relative ≥20% increase in left ventricular end‐diastolic volume index (LVEDVI). LVR in chronic phase was found in 34 patients (18.7%) whose platelet reactivity was significantly higher than those without LVR (259.6 ± 61.5 and 213.1 ± 74.8 P2Y12 reaction units [PRU]; P = 0.001). The occurrence of LVR did not differ between patients with STEMI and patients with NSTEMI (21.5% and 14.7%; P = 0.33). The optimal cut‐off value of platelet reactivity for discriminating LVR was ≥245 PRU. LVEDVI significantly decreased at chronic phase in patients without high platelet reactivity (<245 PRU) (from 49.2 ± 13.5 to 45.4 ± 15.8 mL/m²; P = 0.02), but not in patients with high platelet reactivity (≥d245 PRU) (P = 0.06). Multivariate logistic analysis showed that high platelet reactivity was an independent predictor of LVR after adjusting for LVEDVI before discharge (odds ratio, 4.13; 95% confidence interval, 1.85–9.79).

Conclusions

High platelet reactivity measured immediately after PCI was a predictor of LVR in patients with AMI during the chronic phase. The role of antiplatelet therapy on inflammation in the myocardium is a promising area for further research.

DOI： 10.1002/ehf2.14100

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ehf2.14100

Overview of the 86th Annual Scientific Meeting of the Japanese Circulation Society - Cardiology Spreading Its Wings.

Kazufumi Nakamura, Toru Miyoshi, Satoshi Akagi, Norihisa Toh, Yukihiro Saito, Yoichi Takaya, Masatoki Yoshida, Koji Nakagawa, Satoshi Kawada, Hironobu Toda, Takashi Miki, Rie Nakayama, Fumi Yokohama, Keishi Ichikawa, Masashi Yoshida, Makiko Taniyama, Nobuhiro Nishii, Teiji Akagi, Hiroshi Morita, Hiroshi Ito

Circulation journal : official journal of the Japanese Circulation Society 86 ( 8 ) 1312 - 1318 2022.7

Language：English Publishing type：Research paper (scientific journal)

The 86thAnnual Scientific Meeting of the Japanese Circulation Society was held in a web-based format on March 11-13, 2022. In accordance with the internationalization policy of the JCS, the meeting was held with the Asian Pacific Society of Cardiology Congress 2022. The main theme was "Cardiology Spreading its Wings". The number of patients with heart failure and other cardiovascular diseases is increasing dramatically, and the fields dealt with by cardiovascular medicine are also greatly expanding. This conference was both intellectually satisfying and exciting for all participants, who numbered over 14,900. The meeting was completed with great success, and the enormous amount of cooperation and support from all involved was greatly appreciated.

DOI： 10.1253/circj.CJ-22-0349

冠動脈疾患を疑われた非アルコール性脂肪性肝疾患における冠動脈周囲脂肪炎症の予後予測効果への検討単施設後ろ向き研究

中島充貴, 三好亨, 市川啓之, 西原大裕, 三木崇史, 戸田洋伸, 吉田雅言, 伊藤浩

日本動脈硬化学会総会プログラム・抄録集 54回 229 - 229 2022.7

Impact of shear wave dispersion slope analysis for assessing the severity of myocarditis. International journal

Naofumi Amioka, Yoichi Takaya, Kazufumi Nakamura, Megumi Kondo, Kaoru Akazawa, Yuko Ohno, Keishi Ichikawa, Rie Nakayama, Yukihiro Saito, Satoshi Akagi, Toru Miyoshi, Masashi Yoshida, Hiroshi Morita, Hiroshi Ito

Scientific reports 12 ( 1 ) 8776 - 8776 2022.5

Language：English Publishing type：Research paper (scientific journal)

This study aimed to elucidate the utility of a novel ultrasound-based technique, shear wave dispersion slope (SWDS) analysis, which estimates tissue viscosity, for evaluating the severity of myocardial inflammation. Experimental autoimmune myocarditis (EAM) at different disease phases [3-week (acute phase): n = 10, 5-week (subacute phase): n = 9, and 7-week (late phase): n = 11] were developed in male Lewis rats. SWDS was measured in the right and the left ventricular free walls (RVFW and LVFW) under a retrograde perfusion condition. Histological myocardial inflammation was evaluated by CD68 staining. The accumulation of CD68-positive cells was severe in the myocardium of the EAM 3-week group. The median (interquartile range) SWDS of RVFW was significantly higher in the EAM 3-week group [9.9 (6.5-11.0) m/s/kHz] than in the control group [5.4 (4.5-6.8) m/s/kHz] (P = 0.034). The median SWDS of LVFW was also significantly higher in the EAM 3-week group [8.1 (6.4-11.0) m/s/kHz] than in the control group [4.4 (4.2-4.8) m/s/kHz] (P = 0.003). SWDS and the percentage of CD68-positive area showed a significant correlation in RVFW (R2 = 0.64, P < 0.001) and LVFW (R2 = 0.73, P < 0.001). This study showed that SWDS was elevated in ventricular walls with acute inflammation and also significantly correlated with the degree of myocardial inflammation. These results suggest the potential of SWDS in estimating the histological severity of acute myocarditis.

DOI： 10.1038/s41598-022-12935-6

Association of Oxidized Low-Density Lipoprotein in Nonalcoholic Fatty Liver Disease with High-Risk Plaque on Coronary Computed Tomography Angiography: A Matched Case-Control Study. International journal

Takahiro Nishihara, Toru Miyoshi, Keishi Ichikawa, Kazuhiro Osawa, Mitsutaka Nakashima, Takashi Miki, Hiroshi Ito

Journal of clinical medicine 11 ( 10 ) 2022.5

Language：English Publishing type：Research paper (scientific journal)

Nonalcoholic fatty liver disease (NAFLD) is a risk factor for the development of atherosclerotic cardiovascular diseases (CVDs), and oxidative stress has been proposed as a shared pathophysiological condition. This study examined whether oxidized low-density lipoprotein (LDL) is involved in the underlying mechanism that links coronary atherosclerosis and NAFLD. This study included 631 patients who underwent coronary computed tomography angiography (CTA) for suspected coronary artery disease. NAFLD was defined on CT images as a liver-to-spleen attenuation ratio of <1.0. Serum-malondialdehyde-modified LDL (MDA-LDL) and coronary CTA findings were analyzed in a propensity-score-matched cohort of patients with NAFLD (n = 150) and those without NAFLD (n = 150). This study analyzed 300 patients (median age, 65 years; 64% men). Patients with NAFLD had higher MDA-LDL levels and a greater presence of CTA-verified high-risk plaques than those without NAFLD. In the multivariate linear regression analysis, MDA-LDL was independently associated with NAFLD (β = 11.337, p = 0.005) and high-risk plaques (β = 12.487, p = 0.007). Increased MDA-LDL may be a mediator between NAFLD and high-risk coronary plaque on coronary CTA. Increased oxidative stress in NAFLD, as assessed using MDA-LDL, may be involved in the development of CVDs.

DOI： 10.3390/jcm11102838

Enhancement of pacing function by HCN4 overexpression in human pluripotent stem cell-derived cardiomyocytes. International journal

Yukihiro Saito, Kazufumi Nakamura, Masashi Yoshida, Hiroki Sugiyama, Satoshi Akagi, Toru Miyoshi, Hiroshi Morita, Hiroshi Ito

Stem cell research & therapy 13 ( 1 ) 141 - 141 2022.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The number of patients with bradyarrhythmia and the number of patients with cardiac pacemakers are increasing with the aging population and the increase in the number of patients with heart diseases. Some patients in whom a cardiac pacemaker has been implanted experience problems such as pacemaker infection and inconvenience due to electromagnetic interference. We have reported that overexpression of HCN channels producing a pacemaker current in mouse embryonic stem cell-derived cardiomyocytes showed enhanced pacing function in vitro and in vivo. The aim of this study was to determine whether HCN4 overexpression in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can strengthen the pacing function of the cells. METHODS: Human HCN4 was transduced in the AAVS1 locus of human induced pluripotent stem cells by nucleofection and HCN4-overexpressing iPSC-CMs were generated. Gene expression profiles, frequencies of spontaneous contraction and pacing abilities of HCN4-overexpressing and non-overexpressing iPSC-CMs in vitro were compared. RESULTS: HCN4-overexpressing iPSC-CMs showed higher spontaneous contraction rates than those of non-overexpressing iPSC-CMs. They responded to an HCN channel blocker and β adrenergic stimulation. The pacing rates against parent iPSC line-derived cardiomyocytes were also higher in HCN4-overexpressing iPSC-CMs than in non-overexpressing iPSC-CMs. CONCLUSIONS: Overexpression of HCN4 showed enhancement of If current, spontaneous firing and pacing function in iPSC-CMs. These data suggest this transgenic cell line may be useful as a cardiac pacemaker.

DOI： 10.1186/s13287-022-02818-y

Pathophysiology and Treatment of Diabetic Cardiomyopathy and Heart Failure in Patients with Diabetes Mellitus

Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Satoshi Akagi, Yukihiro Saito, Kentaro Ejiri, Naoaki Matsuo, Keishi Ichikawa, Keiichiro Iwasaki, Takanori Naito, Yusuke Namba, Masatoki Yoshida, Hiroki Sugiyama, Hiroshi Ito

International Journal of Molecular Sciences 23 ( 7 ) 3587 - 3587 2022.3

Publishing type：Research paper (scientific journal) Publisher：MDPI AG

There is a close relationship between diabetes mellitus and heart failure, and diabetes is an independent risk factor for heart failure. Diabetes and heart failure are linked by not only the complication of ischemic heart disease, but also by metabolic disorders such as glucose toxicity and lipotoxicity based on insulin resistance. Cardiac dysfunction in the absence of coronary artery disease, hypertension, and valvular disease is called diabetic cardiomyopathy. Diabetes-induced hyperglycemia and hyperinsulinemia lead to capillary damage, myocardial fibrosis, and myocardial hypertrophy with mitochondrial dysfunction. Lipotoxicity with extensive fat deposits or lipid droplets is observed on cardiomyocytes. Furthermore, increased oxidative stress and inflammation cause cardiac fibrosis and hypertrophy. Treatment with a sodium glucose cotransporter 2 (SGLT2) inhibitor is currently one of the most effective treatments for heart failure associated with diabetes. However, an effective treatment for lipotoxicity of the myocardium has not yet been established, and the establishment of an effective treatment is needed in the future. This review provides an overview of heart failure in diabetic patients for the clinical practice of clinicians.

DOI： 10.3390/ijms23073587

LCZ696 ameliorates doxorubicin-induced cardiomyocyte toxicity in rats. International journal

Toru Miyoshi, Kazufumi Nakamura, Naofumi Amioka, Omer F Hatipoglu, Tomoko Yonezawa, Yukihiro Saito, Masashi Yoshida, Satoshi Akagi, Hiroshi Ito

Scientific reports 12 ( 1 ) 4930 - 4930 2022.3

Language：English Publishing type：Research paper (scientific journal)

Doxorubicin (DOX)-based chemotherapy induces cardiotoxicity, which is considered the main bottleneck for its clinical application. In this study, we investigated the potential benefit of LCZ696, an angiotensin receptor-neprilysin inhibitor against DOX-induced cardiotoxicity in rats and H9c2 cells and determined whether the mechanism underlying any such effects involves its antioxidant activity. Male Sprague-Dawley rats were randomly separated into four groups, each consisting of 15 rats (DOX (1.5 mg/kg/day intraperitoneally for 10 days followed by non-treatment for 8 days); DOX + valsartan (31 mg/kg/day by gavage from day 1 to day 18); DOX + LCZ696 (68 mg/kg/day by gavage from day 1 to day 18); and control (saline intraperitoneally for 10 days). DOX-induced elevation of cardiac troponin T levels on day 18 was significantly reduced by LCZ696, but not valsartan. The DOX-induced increase in myocardial reactive oxygen species (ROS) levels determined using dihydroethidium was significantly ameliorated by LCZ696, but not valsartan, and was accompanied by the suppression of DOX-induced increase in p47phox. LCZ696 recovered the DOX-induced decrease in phosphorylation of adenosine monophosphate-activated protein kinase and increased the ratio of Bax and Bcl-2. In H9c2 cardiomyocytes, LCZ696 reduced DOX-induced mitochondrial ROS generation and improved cell viability more than valsartan. Our findings indicated that LCZ696 ameliorated DOX-induced cardiotoxicity in rat hearts in vivo and in vitro, possibly by mediating a decrease in oxidative stress.

DOI： 10.1038/s41598-022-09094-z

High pericoronary adipose tissue attenuation on computed tomography angiography predicts cardiovascular events in patients with type 2 diabetes mellitus: post-hoc analysis from a prospective cohort study. International journal

Keishi Ichikawa, Toru Miyoshi, Kazuhiro Osawa, Mitsutaka Nakashima, Takashi Miki, Takahiro Nishihara, Hironobu Toda, Masatoki Yoshida, Hiroshi Ito

Cardiovascular diabetology 21 ( 1 ) 44 - 44 2022.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) is a non-invasive biomarker for pericoronary inflammation. We aimed to investigate the prognostic value of PCAT attenuation in patients with type 2 diabetes mellitus (T2DM). METHODS: We included 333 T2DM patients (mean age, 66 years; male patients, 211; mean body mass index, 25 kg/m2) who underwent clinically indicated coronary CTA and examined their CT findings, coronary artery calcium score, pericardial fat volume, stenosis (> 50% luminal narrowing), high-risk plaque features of low-attenuation plaque and/or positive remodelling and/or spotty calcification, and PCAT attenuation. We assessed PCAT attenuation in Hounsfield units (HU) of proximal 40-mm segments of the left anterior descending artery (LAD) and right coronary artery (RCA). Cardiovascular events were defined as cardiac death, hospitalisation for acute coronary syndrome, late coronary revascularisation, and hospitalisation for heart failure. RESULTS: During a median follow-up of 4.0 years, we observed 31 cardiovascular events. LAD-PCAT attenuation was significantly higher in patients with cardiovascular events than in those without (- 68.5 ± 6.5 HU vs - 70.8 ± 6.1 HU, p = 0.045), whereas RCA-PCAT attenuation was not (p = 0.089). High LAD-PCAT attenuation (> - 70.7 HU; median value) was significantly associated with cardiovascular events in a model that included adverse CTA findings, such as significant stenosis and/or high-risk plaque (hazard ratio; 2.69, 95% confidence interval; 1.17-0.20, p = 0.020). After adding LAD-PCAT attenuation to the adverse CTA findings, the C-statistic and global chi-square values increased significantly from 0.65 to 0.70 (p = 0.037) and 10.9-15.0 (p = 0.043), respectively. CONCLUSIONS: In T2DM patients undergoing clinically indicated coronary CTA, high LAD-PCAT attenuation could significantly predict cardiovascular events. This suggests that assessing LAD-PCAT attenuation can help physicians identify high-risk T2DM patients.

DOI： 10.1186/s12933-022-01478-9

2型糖尿病および左室駆出率が保たれた心不全患者におけるLuseogliflozinの推定血漿量への影響(Effects of Luseogliflozin on Estimated Plasma Volume in Patients with Type 2 Diabetes and Heart Failure with Preserved Ejection Fraction)

中島充貴, 三好亨, 江尻健太郎, 木原一, 幡芳樹, 長野俊彦, 高石篤志, 戸田洋伸, 赤木達, 櫻木悟, 皆川太郎, 伊藤浩

日本循環器学会学術集会抄録集 86回 JO09 - 1 2022.3

CTにおけるPericoronary Fat Attenuation Indexは虚血性心疾患の既往がない患者における心不全入院を予測する(Pericoronary Fat Attenuation Index on Computed Tomography Predicts Hospitalization for Heart Failure in Patients without History of Ischemic Heart Disease)

中島充貴, 三好亨, 市川啓之, 西原大裕, 三木崇史, 高谷陽一, 横濱ふみ, 中山理絵, 杜徳尚, 伊藤浩

日本循環器学会学術集会抄録集 86回 MPJ05 - 2 2022.3

Effects of luseogliflozin on estimated plasma volume in patients with heart failure with preserved ejection fraction. International journal

Mitsutaka Nakashima, Toru Miyoshi, Kentaro Ejiri, Hajime Kihara, Yoshiki Hata, Toshihiko Nagano, Atsushi Takaishi, Hironobu Toda, Seiji Nanba, Yoichi Nakamura, Satoshi Akagi, Satoru Sakuragi, Taro Minagawa, Yusuke Kawai, Nobuhiro Nishii, Soichiro Fuke, Masaki Yoshikawa, Kazufumi Nakamura, Hiroshi Ito

ESC heart failure 9 ( 1 ) 712 - 720 2022.2

Language：English Publishing type：Research paper (scientific journal)

AIMS: Sodium glucose co-transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: This study was a post-hoc analysis of the MUSCAT-HF trial (UMIN000018395), a multicentre, prospective, open-label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed-effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group-difference -6.43% [95% confidence interval (CI): -9.11 to -3.74]}, at Week 12 [-8.73% (95%CI: -11.40 to -6.05)], and at Week 24 [-11.02% (95%CI: -13.71 to -8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log-transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019). CONCLUSIONS: Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF.

DOI： 10.1002/ehf2.13683

2型糖尿病患者におけるCTを用いた冠動脈周囲脂肪の炎症イメージングによるリスク評価

市川啓之, 三好亨, 中島充貴, 西原大裕, 三木崇史, 中村一文, 森田宏, 伊藤浩

日本内科学会雑誌 111 ( 臨増 ) 158 - 158 2022.2

Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms. International journal

Naofumi Amioka, Toru Miyoshi, Tomoko Yonezawa, Megumi Kondo, Satoshi Akagi, Masashi Yoshida, Yukihiro Saito, Kazufumi Nakamura, Hiroshi Ito

Frontiers in cardiovascular medicine 9 904215 - 904215 2022

Language：English Publishing type：Research paper (scientific journal)

Background: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) agonist, on AAA formation and rupture. Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE - / - mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS). Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-α in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPARα significantly attenuated the anti-oxidative effect of pemafibrate. Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.

DOI： 10.3389/fcvm.2022.904215

Role of coronary computed tomography angiography (CTA) post the ISCHEMIA trial: Precision prevention based on coronary CTA-derived coronary atherosclerosis. International journal

Rine Nakanishi, Kazuhiro Osawa, Akira Kurata, Toru Miyoshi

Journal of cardiology 2021.12

Language：English Publishing type：Research paper (scientific journal)

The International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial has been recently published and suggested the importance of the selection of patients at high risk for future cardiovascular disease events and the enhancing optimal medical therapy. In the ISCHEMIA trial, coronary computed tomography angiography (CTA) was performed in most of the patients to exclude high-risk patients and those without obstructive coronary artery disease (CAD) who should not be randomized. Coronary CTA has been widely used as a non-invasive diagnostic modality to assess patients with suspected CAD. Currently, the international guidelines allow use of coronary CTA as a class I recommendation for patients with chest pain. Besides, in the numerous multicenter trials, the emerging role of coronary CTA has proven that it could soon become the standard for monitoring CAD and identifying patients at high risk of future cardiovascular events. In this review article, we summarize the current evidence on coronary CTA and the potential role of coronary CTA after the ISCHEMIA trial for patients with CAD. Risk assessment using detailed CAD data obtained non-invasively and prevention of future cardiovascular events through improved medical care will become increasingly essential for the precision treatment and prevention of CAD in patients.

DOI： 10.1016/j.jjcc.2021.12.006

Arterial stiffness in health and disease: The role of cardio-ankle vascular index. International journal

Toru Miyoshi, Hiroshi Ito

Journal of cardiology 78 ( 6 ) 493 - 501 2021.12

Language：English Publishing type：Research paper (scientific journal)

Arterial stiffness increases with age, as well as in various pathological states, including obesity, diabetes mellitus, smoking, and dyslipidemia, and it has important consequences for cardiovascular health. Arterial stiffness plays a central role in hemodynamic dysfunction characterized by excess pulsatility; specifically, it leads to heart failure, cerebrovascular disease, and renal failure. Among measures of arterial stiffness, carotid-femoral pulse wave velocity is considered as the reference standard; however, it has not been incorporated into routine clinical practice. Cardio-ankle vascular index (CAVI), which is a marker of arterial stiffness measured from the origin of the aorta to the ankle, was developed in 2004. CAVI is based on stiffness parameter β, which is theoretically independent of blood pressure at the time of measurement. CAVI applies stiffness parameter β to arterial segments between the heart and ankle. The measurement of CAVI is simple and well-standardized, and its reproducibility and accuracy are acceptable. Several studies have demonstrated that CAVI is high in patients with various atherosclerotic risk factors, and treatment of cardiovascular risk factors and lifestyle modifications improve CAVI. Several prospective studies have investigated the association between CAVI and future cardiovascular events in the general population and in patients with cardiovascular risk factors. A cut-off value of 9.0 is proposed for predicting patients at a high risk of cardiovascular events. From this review, it is clear that CAVI may be useful in the prevention of cardiovascular disease.

DOI： 10.1016/j.jjcc.2021.07.011

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