研究者詳細 - 神津　英至

論文 - 神津　英至

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Abrupt Onset of Cardiac Tamponade in Sarcoidosis.

Toshiyuki Yano, Shin Hisahara, Nobutaka Nagano, Takahiro Noto, Toshifumi Ogawa, Ryo Nishikawa, Masayuki Koyama, Hidemichi Kouzu, Atsuko Muranaka, Akiyoshi Hashimoto, Shun Shimohama, Tetsuji Miura

International heart journal ( (一社)インターナショナルハートジャーナル刊行会 ) 62 ( 5 ) 1176 - 1181 2021年09月 [国内誌]

Sarcoidosis is a systemic inflammatory disease characterized by the formation of noncaseating epithelioid granulomas. Multiple organs, including the lung, eyes, and skin, are involved in this disorder, and cardiac involvement is a major cause of morbidity and mortality in patients with this disorder. We present the case history of a 22-year-old man with neurosarcoidosis complicated by abrupt onset of cardiac tamponade. Cardiac tamponade is a rare but potentially fatal manifestation of sarcoidosis, which is treatable with glucocorticoid therapy. Including the present case, previously reported cases of sarcoidosis with cardiac tamponade are reviewed to delineate its clinical characteristics.

DOI PubMed

Novel prediction equation for appendicular skeletal muscle mass estimation in patients with heart failure: Potential application in daily clinical practice.

Satoshi Katano, Toshiyuki Yano, Katsuhiko Ohori, Nobutaka Nagano, Suguru Honma, Kanako Shimomura, Tomoyuki Ishigo, Ayako Watanabe, Remi Honma, Takefumi Fujito, Masayuki Koyama, Hidemichi Kouzu, Akiyoshi Hashimoto, Masaki Katayose, Tetsuji Miura

European journal of preventive cardiology 28 ( 9 ) e18-e21 2021年08月 [国際誌]

DOI PubMed

Reduction in GLP-1 secretory capacity may be a novel independent risk factor of coronary artery stenosis.

Chihiro Nagase, Masaya Tanno, Hidemichi Kouzu, Takayuki Miki, Junichi Nishida, Naoto Murakami, Nobuaki Kokubu, Nobutaka Nagano, Ryo Nishikawa, Nobuhiro Yoshioka, Tohru Hasegawa, Hiroyuki Kita, Akihito Tsuchida, Hirofumi Ohnishi, Tetsuji Miura

Scientific reports 11 ( 1 ) 15578 - 15578 2021年08月 [国際誌]

Multiple factors regulate glucagon-like peptide-1 (GLP-1) secretion, but a group of apparently healthy subjects showed blunted responses of GLP-1 secretion in our previous study. In this study, we examined whether the reduction in GLP-1 secretory capacity is associated with increased extent of coronary artery stenosis in non-diabetic patients. Non-diabetic patients who were admitted for coronary angiography without a history of coronary interventions were enrolled. Coronary artery stenosis was quantified by Gensini score (GS), and GS ≥ 10 was used as an outcome variable based on its predictive value for cardiovascular events. The patients (mean age, 66.5 ± 8.8 years; 71% males, n = 173) underwent oral 75 g-glucose tolerant tests for determination of glucose, insulin and active GLP-1 levels. The area under the curve of plasma active GLP-1 (AUC-GLP-1) was determined as an index of GLP-1 secretory capacity. AUC-GLP-1 was not correlated with fasting glucose, AUC-glucose, serum lipids or indices of insulin sensitivity. In multivariate logistic regression analysis for GS ≥ 10, AUC-GLP-1 < median, age and hypertension were selected as explanatory variables, though fasting GLP-1 level was not selected. The findings suggest that reduction in GLP-1 secretory capacity is a novel independent risk factor of coronary stenosis.

DOI PubMed

Does renin-angiotensin system inhibition have impacts on muscle mass and bone mineral density in heart failure patients?

Satoshi Katano, Toshiyuki Yano, Masaki Shimizu, Katsuhiko Ohori, Hidemichi Kouzu, Masayuki Koyama, Ryohei Nagaoka, Takuya Inoue, Yuhei Takamura, Tomoyuki Ishigo, Hiroyuki Takashima, Masaki Katayose, Hirofumi Ohnishi, Tetsuji Miura

ESC heart failure 8 ( 4 ) 2617 - 2624 2021年08月 [国際誌]

AIMS: Results of experimental studies have indicated the possibility of muscle and bone mass being negatively regulated by renin-angiotensin system (RAS) activation, but that possibility has not been analysed in patients with heart failure (HF). METHODS AND RESULTS: Data for HF patients who received a dual-energy X-ray absorptiometry scan in our hospital were reviewed. Propensity scores for the use of RAS inhibitors (RASIs) were calculated using a multivariate logistic regression model to minimize selection bias. One hundred sixty pairs of patients were extracted. Plasma aldosterone concentration was significantly lower in the RASIs group than in the no-RASIs group (119 [IQR 71-185] vs. 94 [IQR 60-131] pg/mL, P = 0.003), confirming RAS inhibition in the RASIs group. Skeletal muscle mass index tended to be higher in the RASIs group than in the non-RASIs group (15.6 [IQR 14.0-17.2] vs. 15.0 [IQR 13.3-16.6] pg/mL, P = 0.065). The proportion of patients with muscle wasting, defined as appendicular skeletal muscle mass indexes of <7.00 and <5.40 kg/m2 for males and females, respectively, was significantly lower in the RASIs group than in the non-RASIs group (53% vs. 64%, P = 0.041). Multivariate logistic regression analysis showed that the no use of RASIs was associated with presence of muscle wasting independently of age, presence of diabetes, renal function, and severity of HF. Bone mineral densities and proportions of patients with osteoporosis were similar in the two groups. CONCLUSIONS: Renin-angiotensin system inhibition is associated with a lower prevalence of muscle wasting in HF patients independently of established risk factors.

DOI PubMed

入院中のエネルギー摂取は高齢心不全患者の栄養状態とは無関係に退院後の全死因死亡率を予測する【JST・京大機械翻訳】

Katano Satoshi, Yano Toshiyuki, Kouzu Hidemichi, Ohori Katsuhiko, Ohori Katsuhiko, Shimomura Kanako, Honma Suguru, Nagaoka Ryohei, Inoue Takuya, Takamura Yuhei, Ishigo Tomoyuki, Watanabe Ayako, Koyama Masayuki, Koyama Masayuki, Nagano Nobutaka, Fujito Takefumi, Nishikawa Ryo, Ohwada Wataru, Hashimoto Akiyoshi, Hashimoto Akiyoshi, Katayose Masaki, Miura Tetsuji

Clinical Research in Cardiology 110 ( 8 ) 1202 - 1220 2021年08月 [国際誌]

OBJECTIVE: Malnutrition is associated with an increased risk of mortality in heart failure (HF) patients. Here, we examined the hypothesis that assessment of energy intake in addition to nutritional status improves the stratification of mortality risk in elderly HF patients. METHODS: We retrospectively examined 419 HF patients aged ≥ 65 years (median 78 years, 49% female). Nutritional status was assessed by the Mini Nutritional Assessment Short Form (MNA-SF), and daily energy intake was calculated from intake during 3 consecutive days before discharge. RESULTS: During a median 1.52-year period (IQR 0.96-2.94 years), 110 patients (26%) died. Kaplan-Meier survival curves showed that patients with low tertile of daily energy intake had a higher mortality rate than did patients with high or middle tertile of daily energy intake. In multivariate Cox regression analyses, low daily energy intake was independently associated with higher mortality after adjustment for the model including age, sex, BNP, Charlson Comorbidity Index, history of HF hospitalization, and cachexia in addition to MNA-SF. Inclusion of both MNA-SF and energy intake into the adjustment model improved the accuracy of prediction of the mortality after discharge (continuous net reclassification improvement, 0.355, p = 0.003; integrated discrimination improvement, 0.029, p = 0.003). Results of a fully adjusted dose-dependent association analysis showed that risk of all-cause mortality was lowest among HF patients who consumed 31.5 kcal/kg/day of energy. CONCLUSIONS: Energy intake during hospital stay is an independent predictor of the mortality in elderly HF patients, and its assessment together with established predictors improves the mortality risk stratification.

DOI PubMed J-GLOBAL

キサンチンオキシドレダクターゼ仲介損傷は圧力過負荷条件下の2型糖尿病ラット心臓における上方制御AMPデアミナーゼにより増幅される【JST・京大機械翻訳】

Igaki Yusuke, Tanno Masaya, Sato Tatsuya, Kouzu Hidemichi, Ogawa Toshifumi, Osanami Arata, Yano Toshiyuki, Kuno Atsushi, Miki Takayuki, Nakamura Takashi, Miura Tetsuji

Journal of Molecular and Cellular Cardiology 154 21 - 31 2021年05月 [国際誌]

BACKGROUND: We previously reported that upregulated AMP deaminase (AMPD) contributes to diastolic ventricular dysfunction via depletion of the adenine nucleotide pool in a rat model of type 2 diabetes (T2DM), Otsuka Long-Evans-Tokushima Fatty rats (OLETF). Meanwhile, AMPD promotes the formation of substrates of xanthine oxidoreductase (XOR), which produces ROS as a byproduct. Here, we tested the hypothesis that a functional link between upregulated AMPD and XOR is involved in ventricular dysfunction in T2DM rats. METHODS AND RESULTS: Pressure-volume loop analysis revealed that pressure overloading by phenylephrine infusion induced severer left ventricular diastolic dysfunction (tau: 14.7 ± 0.8 vs 12.5 ± 0.7 msec, left ventricular end-diastolic pressure: 18.3 ± 1.5 vs 12.2 ± 1.3 mmHg, p < 0.05) and ventricular-arterial uncoupling in OLETF than in LETO, non-diabetic rats, though the baseline parameters were comparable in the two groups. While the pressure overload did not affect AMPD activity, it increased XOR activity both in OLETF and LETO, with OLETF showing significantly higher XOR activity than that in LETO (347.2 ± 17.9 vs 243.2 ± 6.1 μg/min/mg). Under the condition of pressure overload, myocardial ATP level was lower, and levels of xanthine and uric acid were higher in OLETF than in LETO. Addition of exogenous inosine, a product of AMP deamination, to the heart homogenates augmented XOR activity. OLETF showed 68% higher tissue ROS levels and 47% reduction in mitochondrial state 3 respiration compared with those in LETO. Overexpression of AMPD3 in H9c2 cells elevated levels of hypoxanthine and ROS and reduced the level of ATP. Inhibition of XOR suppressed the production of tissue ROS and mitochondrial dysfunction and improved ventricular function under the condition of pressure overload in OLETF. CONCLUSIONS: The results suggest that increases in the activity of XOR and the formation of XOR substrates by upregulated AMPD contribute to ROS-mediated diastolic ventricular dysfunction at the time of increased cardiac workload in diabetic hearts.

DOI PubMed J-GLOBAL

心不全患者における形態指標から推定した四肢骨格筋量の予後予測能の検討

本間傑, 片野唆敏, 矢野俊之, 長岡凌平, 神津英至, 大堀克彦, 渡辺絢子, 石郷友之, 大和田渉, 西川諒, 永野伸卓, 小山雅之, 片寄正樹, 橋本暁佳, 小林史, 善岡信博, 三浦哲嗣

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 ) 85回 CP06 - 7 2021年03月

高体脂肪量は心不全患者の心臓事象のより低いリスクを予測する:肥満パラドックスの説明【JST・京大機械翻訳】

Ohori Katsuhiko, Ohori Katsuhiko, Yano Toshiyuki, Katano Satoshi, Kouzu Hidemichi, Honma Suguru, Shimomura Kanako, Inoue Takuya, Takamura Yuhei, Nagaoka Ryohei, Koyama Masayuki, Koyama Masayuki, Nagano Nobutaka, Fujito Takefumi, Nishikawa Ryo, Ishigo Tomoyuki, Watanabe Ayako, Hashimoto Akiyoshi, Hashimoto Akiyoshi, Miura Tetsuji

BMC Geriatrics (Web) 21 ( 1 ) 16 - 16 2021年01月 [国際誌]

BACKGROUND: Although high body mass index (BMI) is a risk factor of heart failure (HF), HF patients with a higher BMI had a lower mortality rate than that in HF patients with normal or lower BMI, a phenomenon that has been termed the "obesity paradox". However, the relationship between body composition, i.e., fat or muscle mass, and clinical outcome in HF remains unclear. METHODS: We retrospectively analyzed data for 198 consecutive HF patients (76 years of age; males, 49%). Patients who were admitted to our institute for diagnosis and management of HF and received a dual-energy X-ray absorptiometry scan were included regardless of left ventricular ejection fraction (LVEF) categories. Muscle wasting was defined as appendicular skeletal muscle mass index < 7.0 kg/m2 in males and < 5.4 kg/m2 in females. Increased percent body fat mass (increased FM) was defined as percent body fat > 25% in males and > 30% in females. RESULTS: The median age of the patients was 76 years (interquartile range [IQR], 67-82 years) and 49% of them were male. The median LVEF was 47% (IQR, 33-63%) and 33% of the patients had heart failure with reduced ejection fraction. Increased FM and muscle wasting were observed in 58 and 67% of the enrolled patients, respectively. During a 180-day follow-up period, 32 patients (16%) had cardiac events defined as cardiac death or readmission by worsening HF or arrhythmia. Kaplan-Meier survival curves showed that patients with increased FM had a lower cardiac event rate than did patients without increased FM (11.4% vs. 22.6%, p = 0.03). Kaplan-Meier curves of cardiac event rates did not differ between patients with and those without muscle wasting (16.5% vs. 15.4%, p = 0.93). In multivariate Cox regression analyses, increased FM was independently associated with lower cardiac event rates (hazard ratio: 0.45, 95% confidence interval: 0.22-0.93) after adjustment for age, sex, diabetes, muscle wasting, and renal function. CONCLUSIONS: High percent body fat mass is associated with lower risk of short-term cardiac events in HF patients.

DOI PubMed J-GLOBAL

Distinct determinants of muscle wasting in nonobese heart failure patients with and without type 2 diabetes mellitus.

Toshiyuki Yano, Satoshi Katano, Hidemichi Kouzu, Ryohei Nagaoka, Takuya Inoue, Yuhei Takamura, Tomoyuki Ishigo, Ayako Watanabe, Katsuhiko Ohori, Masayuki Koyama, Nobutaka Nagano, Takefumi Fujito, Ryo Nishikawa, Akiyoshi Hashimoto, Tetsuji Miura

Journal of diabetes 13 ( 1 ) 7 - 18 2021年01月 [国際誌]

BACKGROUND: Muscle wasting, that is, reduction in muscle mass, is frequently observed in patients with chronic heart failure (CHF) and diabetes mellitus (DM). METHODS: We retrospectively examined 185 patients with CHF (median age of 71 years [interquartile range, 61-78 years]; 64% male) who received a dual-energy X-ray absorptiometry scan for assessment of appendicular skeletal muscle mass index (ASMI). RESULTS: Seventy patients with CHF (38%) had DM. Patients with DM had higher prevalences of ischemic heart disease and hypertension, lower levels of estimated glomerular filtration rate (eGFR) and ASMI, and higher levels of plasma renin activity (PRA) than did patients without DM. In simple regression analyses, ASMI was positively correlated with the Mini Nutritional Assessment Short Form (MNA-SF) score and levels of hemoglobin, eGFR, and fasting plasma insulin and was negatively correlated with levels of N-terminal pro B-type natriuretic peptide, PRA, and cortisol. In multiple linear regression analyses, age, MNA-SF score, DM, fasting plasma insulin level, and PRA were independently associated with ASMI. When multiple linear regression analyses were separately performed in a non-DM group and a DM group, MNA-SF score and fasting plasma insulin level were independent variables for ASMI in both groups. PRA was independently associated with ASMI in the DM group but not in the non-DM group, whereas cortisol concentration was independently associated with ASMI only in the non-DM group. CONCLUSIONS: In addition to malnutrition and reduction in plasma insulin, renin-angiotensin system activation may be responsible for the development of muscle wasting in CHF patients with DM.

DOI PubMed

慢性心不全患者での骨粗鬆症の臨床的リスク因子と予後への影響

Katano Satoshi, Yano Toshiyuki, Tsukada Takanori, Kouzu Hidemichi, Honma Suguru, Inoue Takuya, Takamura Yuhei, Nagaoka Ryohei, Ishigo Tomoyuki, Watanabe Ayako, Ohori Katsuhiko, Ohori Katsuhiko, Koyama Masayuki, Nagano Nobutaka, Fujito Takefumi, Nishikawa Ryo, Takashima Hiroyuki, Hashimoto Akiyoshi, Hashimoto Akiyoshi, Katayose Masaki, Katayose Masaki, Miura Tetsuji

Circulation Journal ( (一社)日本循環器学会 ) 84 ( 12 ) 2224 - 2234 2020年11月 [国内誌]

BACKGROUND: The clinical significance of osteoporosis in chronic heart failure (CHF) remains unclear.Methods and Results:A total of 303 CHF patients (75 years, [interquartile range (IQR) 66-82 years]; 41% female) were retrospectively examined. Bone mineral densities (BMDs) at the lumbar spine, femoral neck, and total femur were measured by using dual-energy X-ray absorptiometry (DEXA), and osteoporosis was diagnosed when the BMD at any of the 3 sites was <70% of the Young Adult Mean percentage (%YAM). The prevalence of osteoporosis in CHF patients was 40%. Patients with osteoporosis were older (79 [IQR, 74-86] vs. 72 [IQR, 62-80] years), included a large percentage of females, had slower gait speed and had a lower body mass index. Multivariate logistic regression analysis indicated that sex, BMI, gait speed, loop diuretics use and no use of direct oral anticoagulants (DOACs) were independently associated with osteoporosis. Kaplan-Meier survival curves showed that the rate of death and heart failure hospitalization was higher in patients with osteoporotic BMD at 2 or 3 sites than in patients without osteoporosis (hazard ratio 3.45, P<0.01). In multivariate Cox regression analyses, osteoporotic BMD at 2 or 3 sites was an independent predictor of adverse events after adjustment for prognostic markers. CONCLUSIONS: Loop diuretics use and no DOACs use are independently associated with osteoporosis in CHF patients. Osteoporosis is a novel predictor of worse outcome in patients with CHF.

DOI PubMed J-GLOBAL

Reply to the comments on "Utility of the sarcopenia index for assessment of muscle mass and nutritional status in patients with chronic heart failure: Comparison with anthropometric parameters".

Koki Abe, Toshiyuki Yano, Satoshi Katano, Katsuhiko Ohori, Tomoyuki Ishigo, Hidemichi Kouzu, Norihito Moniwa, Tetsuji Miura

Geriatrics & gerontology international ( John Wiley & Sons Australia, Ltd ) 20 ( 10 ) 998 - 999 2020年10月 [国内誌]

DOI PubMed

インフルエンザワクチン接種後の血液動態崩壊:ワクチン誘発劇症心筋炎?【JST・京大機械翻訳】

Nagano Nobutaka, Yano Toshiyuki, Fujita Yugo, Koyama Masayuki, Koyama Masayuki, Hasegawa Ryo, Nakata Jun, Nishikawa Ryo, Murakami Naoto, Fujito Takefumi, Mochizuki Atsushi, Kouzu Hidemichi, Muranaka Atsuko, Kokubu Nobuaki, Miura Tetsuji

Canadian Journal of Cardiology 36 ( 9 ) 1554.e5-1554.e7 2020年09月 [国際誌]

A 14-year-old girl with cardiopulmonary arrest was referred to our hospital. She had received an injection of inactivated influenza vaccine 7 days before the referral. Her cardiac rhythm was pulseless wide QRS tachycardia, and mechanical circulatory support was immediately begun. Results of endomyocardial biopsy showed that there was massive infiltration of CD3- and CD68-positive cells and various degrees of cardiomyocyte necrosis in all of 3 endomyocardial specimens, whereas infiltration of eosinophils or giant cells was not observed. A histologic diagnosis of lymphocytic myocarditis was made. Acute myocarditis is a rare but potentially fatal complication of the influenza vaccination.

DOI PubMed J-GLOBAL

心不全患者におけるクレアチニンベースの方程式による糸球体濾過率の過大評価は,新規スコアリングシステムにより予測される

Ishigo Tomoyuki, Katano Satoshi, Yano Toshiyuki, Kouzu Hidemichi, Ohori Katsuhiko, Ohori Katsuhiko, Nakata Hiromasa, Nonoyama Masatoshi, Inoue Takuya, Takamura Yuhei, Nagaoka Ryohei, Kondo Fuki, Nakano Keita, Takada Ryo, Kitagawa Manabu, Kimyo Tomoko, Miura Tetsuji

Geriatrics & Gerontology International ( John Wiley & Sons Australia, Ltd ) 20 ( 8 ) 752 - 758 2020年08月 [国内誌]

AIMS: Creatinine-based estimated glomerular filtration rate (eGFRcre) has been shown to overestimate the glomerular filtration rate (GFR) when it is compared with cystatin C-based estimated GFR (eGFRcys) in older people. We investigated clinical determinants of GFR overestimation by eGFRcre and developed a score for prediction of GFR overestimation (OE) in heart failure patients. METHODS: We retrospectively examined 244 Japanese heart failure patients (aged 72.2 ± 13.1 years; 48% women) who had no known extrarenal factors that affect serum cystatin C concentration. eGFR OE by eGFRcre was defined as eGFRcre being ≥120% of cystatin C-based eGFR. RESULTS: The proportion of heart failure patients with OE was 14.3%. Patients with OE were older, had lower body weight and total skeletal muscle mass than those in patients without OE. Laboratory examinations showed that hemoglobin concentration was lower, and the ratio of blood urea nitrogen-to-creatinine was higher in patients with OE than in patients without OE. In multivariate regression analysis, body weight (<63.0 kg in men and <42.0 kg in women), hemoglobin level (<12.4 g/dL in men and <11.0 g/dL in women) and ratio of blood urea nitrogen-to-creatinine (>26.5) in addition to skeletal muscle mass were independently associated with OE. A score calculated by using cut-off levels of body weight, hemoglobin concentration and ratio of blood urea nitrogen-to-creatinine predicted OE with a sensitivity of 97.1% and a specificity of 98.1%. CONCLUSION: Overestimation of GFR by eGFRcre is predictable by a novel scoring system, which might be useful for the detection of patients who require cystatin C-based eGFR measurement for accurate assessment of renal function. Geriatr Gerontol Int 2020; 20: 752-758.

DOI PubMed J-GLOBAL

重症心不全の免疫グロブリン軽鎖アミロイドーシス患者における予後の評価:右心室機能の予測値

Nagano Nobutaka, Yano Toshiyuki, Fujita Yugo, Kouzu Hidemichi, Koyama Masayuki, Koyama Masayuki, Ikeda Hiroshi, Yasui Kenji, Muranaka Atsuko, Nishikawa Ryo, Takahashi Ryo, Kishiue Naohiro, Yuda Satoshi, Miura Tetsuji

Heart and Vessels (Web) ( シュプリンガー・ジャパン(株) ) 35 ( 4 ) 521 - 530 2020年04月 [国内誌]

Although the benefit of updated therapeutic regimens, including bortezomib, on the survival of immunoglobulin light chain (AL) amyloidosis patients with heart failure (HF) has been reported, predictors of mortality in the patients treated with the updated therapy remain unclear. We retrospectively enrolled AL amyloidosis patients who had severe HF at the time of diagnosis and received the updated therapy, including bortezomib (n = 19, 61 ± 6 years old, 68% male). Severe HF was defined as the presence of both NYHA functional class III or IV and BNP > 200 pg/ml or NT-pro-BNP > 900 pg/ml. One-year mortality rate during follow-up after commencement of the treatment was 37%. Left ventricular morphological parameters and indexes of left ventricular diastolic function on admission were similar in the non-survivors and survivors. However, non-survivors had higher incidences of atrial fibrillation and ventricular tachycardia, higher serum total bilirubin levels (1.34 ± 0.55 vs. 0.61 ± 0.29 mg/dl), higher right atrial volume index (RAVI 49.7 ± 29.9 vs. 27.3 ± 6.8 ml/m2), lower tricuspid annular peak velocities during systole (RVs' 8.0 ± 1.8 vs. 11.6 ± 3.7 cm/sec) and late diastole (RVa' 3.4 ± 0.9 vs. 11.4 ± 5.3 cm/sec), and larger inferior vena cava dimension (22.7 ± 6.4 vs. 16.3 ± 4.9 mm) than those in survivors. Kaplan-Meier curve analyses showed that larger RAVI and lower RVs' and RVa', but not left ventricular systolic/diastolic dysfunction, predicted higher mortality during 1-year follow-up. The present results suggest that the presence of right-sided heart abnormality on admission is associated with high 1-year mortality in AL amyloidosis patients with severe HF under the updated therapeutic regimens.

DOI PubMed J-GLOBAL

Novel prediction equation for appendicular skeletal muscle mass estimation in patients with heart failure: Potential application in daily clinical practice.

European journal of preventive cardiology 2047487320904236 - 2047487320904236 2020年02月 [国際誌]

DOI PubMed

mTORC1阻害はRIP1阻害媒介TFeB活性化を介して壊死症を減弱する【JST・京大機械翻訳】

Abe Koki, Yano Toshiyuki, Tanno Masaya, Miki Takayuki, Kuno Atsushi, Kuno Atsushi, Sato Tatsuya, Sato Tatsuya, Kouzu Hidemichi, Nakata Kei, Ohwada Wataru, Kimura Yukishige, Sugawara Hirohito, Shibata Satoru, Igaki Yusuke, Ino Shoya, Miura Tetsuji

Biochimica et Biophysica Acta 1865 ( 12 ) 165552 - 165552 2019年12月 [国際誌]

Accumulating evidence indicates that necroptosis contributes to cardiovascular diseases. We recently reported suppression of autophagy by necroptotic signals in cardiomyocytes and protective action of rapamycin. Here we examined the mechanism by which mTORC1 inhibition protects cardiomyocytes from necroptosis. Necroptosis of H9c2 cells was induced by treatment with tumor necrotic factor-α (TNF) and z-VAD-fmk (zVAD), and the extent of necroptosis was determined as the level of LDH release (as % of total). TNF/zVAD increased RIP1-RIP3 interaction and LDH release from 3.4 ± 1.3% to 46.1 ± 2.3%. The effects of TNF/zVAD were suppressed by an mTORC1 inhibitor, rapamycin, and an mTORC1/2 inhibitor, Ku-0063794, but not by a p70s6K inhibitor, PF-4708671. Protection by rapamycin was not abolished by inhibitors of TAK1, IKKα/β, and cIAP, endogenous necroptosis suppressors upstream of RIP1. Rapamycin and Ku-0063794 suppressed TNF/zVAD-induced RIP1-Ser166 phosphorylation and increased phosphorylation of RIP1-Ser320, an inhibitory phosphorylation site, though such an effect on RIP1-Ser320 was not observed for PF-4708671. Protective effects of rapamycin on TNF/zVAD-induced RIP1-RIP3 binding and necroptosis were undetected in cells transfected with RIP1-S320A. In TNF/zVAD-treated cells, rapamycin and a RIP1 inhibitor, necrostatin-1, increased nuclear localization of transcriptional factor EB (TFEB) and promoted autolysosome formation from autophagosomes in a TFEB-dependent manner. Knockdown of TFEB expression attenuated rapamycin-induced protection from necroptosis in TNF/zVAD-treated cells. The results suggest that mTORC1 inhibition promotes autophagy and protects cardiomyocytes from necroptosis by a TFEB-dependent mechanism and that inhibition of RIP1 by increased phosphorylation at Ser320 is crucial in the cardiomyocyte protection afforded by mTORC1 inhibition.

DOI PubMed J-GLOBAL

肺血管抵抗と右心室機能の心エコーでの組み合わせ評価による肺動脈高血圧症のリスク分類

Kawamukai Mina, Kawamukai Mina, Hashimoto Akiyoshi, Hashimoto Akiyoshi, Koyama Masayuki, Nagano Nobutaka, Nishida Junichi, Mochizuki Atsushi, Kouzu Hidemichi, Muranaka Atsuko, Kokubu Nobuaki, Nagahara Daigo, Yuda Satoshi, Tsuchihashi Kazufumi, Tsuchihashi Kazufumi, Miura Tetsuji

Heart and Vessels (Web) ( シュプリンガー・ジャパン(株) ) 34 ( 11 ) 1789 - 1800 2019年11月 [国内誌]

Which combination of clinical parameters improves the prediction of prognosis in patients with pulmonary arterial hypertension (PAH) remains unclear. We examined whether combined assessment of pulmonary vascular resistance and right ventricular function by echocardiography is useful for classifying risks in PAH. In 41 consecutive patients with PAH (mean age of 48.9 ± 17.3 years, 31 females), a 6-min walk test, pulmonary function test, and echocardiography were performed at baseline and during PAH-specific therapies. The study endpoint was defined as a composite of cardiovascular death and hospitalization for PAH and/or right ventricular failure. During a follow-up period of 9.2 ± 8.7 months, 18 patients reached the endpoint. Multivariate regression analysis showed that the ratio of tricuspid regurgitation pressure gradient to the time-velocity integral of the right ventricular outflow tract (TRPG/TVI) and tricuspid annular plane systolic excursion (TAPSE) during PAH-specific treatment were independent prognostic predictors of the endpoint. Using cutoff values indicated by receiver operating characteristic analysis, the patients were divided into four subsets. Multivariate analyses by Cox's proportional hazards model adjusted for age, sex and body mass index indicated that subset 4 (TRPG/TVI ≥ 3.89 and TAPSE ≤ 18.9 mm) had a significantly higher event risk than did subset 1 (TRPG/TVI < 3.89 and TAPSE > 18.9 mm): HR = 25.49, 95% CI 4.70-476.97, p < 0.0001. Combined assessment of TRPG/TVI and TAPSE during adequate PAH-specific therapies enables classification of risks for death and/or progressive right heart failure in PAH.

DOI PubMed J-GLOBAL

Vanishing Cardiac Tumor: Cardiac Involvement in Methotrexate-Associated Lymphoproliferative Disorders.

Naohiro Kishiue, Toshiyuki Yano, Masayuki Koyama, Ryo Nishikawa, Nobutaka Nagano, Hidemichi Kouzu, Nobuaki Kokubu, Ryota Kawamura, Atsuko Muranaka, Shohei Kikuchi, Akihito Tsuchida, Tetsuji Miura

Circulation. Cardiovascular imaging 12 ( 11 ) e009689 2019年11月 [国際誌]

DOI PubMed

Utility and safety of tocilizumab in Takayasu arteritis with severe heart failure and muscle wasting.

Toshiyuki Yano, Arata Osanami, Masaki Shimizu, Satoshi Katano, Nobutaka Nagano, Hidemichi Kouzu, Masayuki Koyama, Atsuko Muranaka, Ryo Harada, Hirosato Doi, Nobuyoshi Kawaharada, Tetsuji Miura

ESC heart failure 6 ( 4 ) 894 - 897 2019年08月 [国際誌]

Takayasu arteritis (TA) is a large vessel vasculitis of unknown aetiology characterized by chronic inflammatory changes of the aorta and its major branches. We report the active TA case who had severe heart failure due to acute myocardial infarction and aortic regurgitation. Bentall procedure was successfully performed, but he had severely depressed left ventricular function and muscle wasting together with vascular inflammation. The treatment with tocilizumab, an interleukin-6 receptor monoclonal antibody, in addition to prednisolone and standard heart failure therapy led to prompt remission of TA activity and improvement of left ventricular function and muscle wasting. Taken together with possible involvement of interleukin-6 in the pathogenesis of heart failure and muscle wasting, inhibition of interleukin-6 receptor signalling by tocilizumab may be a safe and reasonable approach in the treatment of active TA with heart failure and muscle wasting.

DOI PubMed

甲状腺炎を合併した分娩後心不全:周産期心筋症の隠された悪化因子?【JST・京大機械翻訳】

Kouzu Hidemichi, Yano Toshiyuki, Nagano Nobutaka, Koyama Masayuki, Ogawa Toshifumi, Fujita Yugo, Muranaka Atsuko, Miura Tetsuji

Canadian Journal of Cardiology 35 ( 6 ) 796.e1-796.e3 2019年06月 [国際誌]

The etiology of peripartum cardiomyopathy (PPCM) remains unestablished, but the involvement of abnormal autoimmunity has been suggested. We report a case of PPCM that was triggered by postpartum thyroiditis. Despite the presence of myocardial damage indicated by cardiac magnetic resonance imaging, the patient's cardiac function completely recovered with the addition of bromocriptine to standard therapies. We discuss the role of thyroid hormones in the development of PPCM through aggravation of a prolactin-dependent antiangiogenic effect, and we argue that more attention should be paid to postpartum thyroiditis as a novel risk factor for PPCM.

DOI PubMed J-GLOBAL

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