論文 - 渡邉 望
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Yokoyama R., Kodama Y., Takamura K., Takahashi M., Tanaka M., Watanabe N., Moritake H.
Journal of Cardiology Cases 2025年
掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology Cases
Exercise stress echocardiography (ESE) is a feasible and valuable tool for evaluating subclinical pulmonary hypertension (PH). However, its utility in patients with unilateral pulmonary branch stenosis remains unclear. We present a case involving a 17-year-old patient with left pulmonary branch stenosis who exhibited exercise-induced PH in the contralateral pulmonary artery as detected by ESE. Standard echocardiography was unable to visualize the left pulmonary artery clearly; therefore, computed tomography was performed, revealing a left pulmonary branch stenosis with a minimum diameter of 4.2 mm. Resting echocardiography showed a pressure gradient of 17 mmHg, calculated using the tricuspid regurgitant velocity. During ESE with a prone ergometer, the slope of the mean pulmonary arterial pressure to systemic cardiac output was 3.1 mmHg/L/min, meeting the diagnostic criteria for exercise-induced PH. The patient underwent stent implantation to treat the left pulmonary branch stenosis. Follow-up ESE demonstrated improvement, with the slope of the mean pulmonary arterial pressure to systemic cardiac output decreasing to 1.5 mmHg/L/min. These findings underscore that ESE is both feasible and effective for assessing subclinical unilateral pulmonary branch stenosis. Learning objective: Patients with congenital unilateral peripheral branch pulmonary artery stenosis usually do not have pulmonary hypertension at rest, and identifying patients who require treatment is challenging. Exercise stress echocardiography can detect latent pulmonary hypertension of the contralateral pulmonary artery in some patients, providing valuable insights for determining treatment indications and evaluating the efficacy of catheter interventions for the stenotic lesion.
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Akashi J, Iwataki M, Nabeshima Y, Onoue T, Hayashi A, Tanaga T, Nishino S, Kimura T, Yano M, Watanabe N, Tsuda Y, Araki M, Shibata Y, Nishimura Y, Otsuji Y, Kataoka M.
Circ Cardiovasc Imaging. 17 ( 3 ) e016239 2024年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation: Cardiovascular Imaging
BACKGROUND: Patients with only moderate atrial secondary mitral regurgitation (asMR) frequently develop heart failure (HF). Mechanisms of HF with moderate asMR and the impact of mild asMR remain unclarified. Although mild/moderate primary mitral regurgitation is compensated by left ventricular (LV) dilatation, the LV is not dilated in asMR. We hypothesized that patients with mild asMR without LV dilatation may have impaired hemodynamics and higher risks of subsequent symptomatic HF deterioration. METHODS: Stroke volume, cardiac output, and systolic pulmonary artery pressure were measured by echocardiography in 142 patients with isolated atrial fibrillation and 30 healthy controls. The prognosis of patients with isolated atrial fibrillation was followed up. RESULTS: In the 142 patients with isolated atrial fibrillation, asMR was no/trivial in 55, mild in 83, moderate in 4, while none had severe asMR. Compared with controls and patients with no/trivial asMR, LV end-diastolic volume index was not increased and hemodynamic parameters were abnormal in patients with mild asMR (LV end-diastolic volume index, 65±6 versus 58±8 versus 60±8 mL/m²; stroke volume index, 42±4 versus 35±4 versus 29±6 mL/m²; P<0.001 versus other 2 groups; cardiac output index, 2.8±0.4 versus 2.8±0.5 versus 2.3±0.6 L/min per m²; P<0.001; systolic pulmonary artery pressure, 21±3 versus 26±5 versus 37±9 mm Hg; P<0.001). Although the event-free rate of HF symptomatic deterioration or hospitalization in patients with no/trivial asMR during a median 13.9 months follow-up was 86.9% and 100%, the rate in mild asMR was 59.4% and 85.0% (P<0.001 or P=0.032), respectively. CONCLUSIONS: In the presence of isolated AF and no compensatory LV dilatation, impaired hemodynamics and higher risks of symptomatic HF deterioration were associated with mild asMR, requiring further studies of causalities.
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Amano M, Izumi C, Toki M, Yanagi Y, Hayashida A, Kawamoto T, Hiraoka A, Fukushima S, Sakaguchi T, Watanabe N, Yoshida K.
Eur Heart J Cardiovasc Imaging 25 ( 6 ) 1 - 11 2024年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：European Heart Journal Cardiovascular Imaging
Aims Although systolic expansion of the annulus has been recognized in Barlow’s disease, the mechanisms of the unique pathological movement of the annulus and its relation to the leaflet augmentation have not yet been clarified. We aimed to investigate the detailed mechanisms of the characteristic mitral apparatus dynamics in Barlow’s disease by frame-by-frame sequential geometric analysis using real-time 3D transoesophageal echocardiography. Methods and results Fifty-three patients with Barlow’s disease and severe mitral regurgitation without torn chordae, as well as 10 controls, were included. We evaluated geometric changes in the mitral complex using 3D transoesophageal echocardiography at five points during systole. To identify early systolic billowing of leaflets, the annulo-leaflet angle was measured. We also performed a more detailed analysis in four consecutive frames just before and after leaflet free-edge prolapse above the annulus plane. The median annulo-leaflet angle of both leaflets in early systole was >0° (above annulus plane) in patients with Barlow’s disease, and billowing of the leaflet body was observed from early systole. The prolapse volume of both leaflets increased markedly from early to mid-systole [1.60 (0.85–2.80) to 4.00 (2.10–6.45) mL; analysis of variance (ANOVA), P < 0.001; post hoc, P < 0.05]. With frame-by-frame analysis, dynamic augmentation of the annulus and leaflets developed between frames just before and just after leaflet free-edge prolapse (ANOVA, P < 0.01; post hoc, P < 0.05). Conclusion In Barlow’s disease, early systolic billowing of the mitral leaflet induces systolic annulus expansion followed by leaflet augmentation and leaflet free-edge prolapse.
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Watanabe N., Ashikaga K.
Annals of Cardiothoracic Surgery 13 ( 1 ) 99 - 101 2024年
担当区分：筆頭著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Annals of Cardiothoracic Surgery
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Direct Oral Anticoagulants Would Be Best Choice for Atrial Fibrillation Patients After Coronary Stenting: Retrospective Study in a Japanese Population. 査読あり
Koiwaya H, Watanabe N, Kuriyama N, Shibata Y.
Kurume Medical Journal 68 ( 2 ) 97 - 106 2023年7月
記述言語：英語 掲載種別：研究論文（学術雑誌）
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Dynamic Nature of the Mitral Valve Morphology: Consideration of the Normal Ranges. 査読あり
Kagiyama N, Maekawara S, Izumi Y, Watanabe N, Otsuji Y, Yoshida K.
J Am Soc Echocardiogr 36 ( 1 ) 125 - 126 2023年6月
掲載種別：研究論文（学術雑誌）
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Leaflet tear or what? A challenging echocardiographic diagnosis after percutaneous mitral valve edge-to-edge repair. 査読あり
Furugen M, Watanabe N, Kimura T, Yano M, Shibata Y.
Journal of Echocardiography 21 ( 1 ) 61 - 62 2023年3月
記述言語：英語 掲載種別：症例報告
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Madhyastha H., Madhyastha R., Chakraborty E., Banerjee K., Shah K., Nakajima Y., Chauhan N.S., Sudhakaran S.L., Ohe K., Muthukaliannan G.K., Gopalakrishnan A.V., Maruyama M., Watanabe N.
International Journal of Molecular Sciences 24 ( 4 ) 2023年2月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Journal of Molecular Sciences
Currently, there is a great demand for the development of nanomedicine aided wound tissue regeneration via silver doped nanoceuticals. Unfortunately, very little research is being carried out on antioxidants-doped silver nanometals and their interaction on the signaling axis during the bio-interface mechanism. In this study, c-phycocyanin primed silver nano hybrids (AgcPCNP) were prepared and analyzed for properties such as cytotoxicity, metal decay, nanoconjugate stability, size expansion, and antioxidant features. Fluctuations in the expression of marker genes during cell migration phenomena in in vitro wound healing scenarios were also validated. Studies revealed that physiologically relevant ionic solutions did not exhibit any adverse effects on the nanoconjugate stability. However, acidic, alkali, and ethanol solutions completely denatured the AgcPCNP conjugates. Signal transduction RT2PCR array demonstrated that genes associated with NFĸB- and PI3K-pathways were significantly (p < 0.5%) altered between AgcPCNP and AgNP groups. Specific inhibitors of NFĸB (Nfi) and PI3K (LY294002) pathways confirmed the involvement of NFĸB signaling axes. In vitro wound healing assay demonstrated that NFĸB pathway plays a prime role in the fibroblast cell migration. In conclusion, the present investigation revealed that surface functionalized AgcPCNP accelerated the fibroblast cell migration and can be further explored for wound healing biomedical applications.
DOI： 10.3390/ijms24043184
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The emerging role of exosomes in innate immunity, diagnosis and therapy 査読あり
Gangadaran P., Madhyastha H., Madhyastha R., Rajendran R.L., Nakajima Y., Watanabe N., Velikkakath A.K.G., Hong C.M., Gopi R.V., Muthukalianan G.K., Valsala Gopalakrishnan A., Jeyaraman M., Ahn B.C.
Frontiers in Immunology 13 1085057 2023年1月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Frontiers in Immunology
Exosomes, which are nano-sized transport bio-vehicles, play a pivotal role in maintaining homeostasis by exchanging genetic or metabolic information between different cells. Exosomes can also play a vital role in transferring virulent factors between the host and parasite, thereby regulating host gene expression and the immune interphase. The association of inflammation with disease development and the potential of exosomes to enhance or mitigate inflammatory pathways support the notion that exosomes have the potential to alter the course of a disease. Clinical trials exploring the role of exosomes in cancer, osteoporosis, and renal, neurological, and pulmonary disorders are currently underway. Notably, the information available on the signatory efficacy of exosomes in immune-related disorders remains elusive and sporadic. In this review, we discuss immune cell-derived exosomes and their application in immunotherapy, including those against autoimmune connective tissue diseases. Further, we have elucidated our views on the major issues in immune-related pathophysiological processes. Therefore, the information presented in this review highlights the role of exosomes as promising strategies and clinical tools for immune regulation.
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Miyoshi M., Watanabe N., Fukuda T., Nishino S., Kimura T., Furugen M., Ashikaga K., Takahashi N., Shibata Y.
Journal of Echocardiography 20 ( 4 ) 201 - 207 2022年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Echocardiography
Background: Successful implantation of the WATCHMAN device requires an accurate understanding of left atrial appendage (LAA) anatomy and orifice dimensions. Racial differences are observed in LAA size when comparing Asians with non-Asians. Methods: A total of 170 patients (123 male, 67.4 ± 9.2 years) with paroxysmal or persistent atrial fibrillation (AF) underwent transesophageal echocardiography before catheter ablation or cardioversion (September 2018 to September 2019). As per the recommendations of the WATCHMAN device, the maximal LAA ostial diameters were measured at multiplane angles of 0°, 45°, 90°, and 135°. Results: The majority of patients (121/170, 71%) had an LAA orifice size within 17–25 mm. Fifteen (8.8%) patients had undersized (< 17 mm) and eight (0.5%) had oversized (> 31 mm) LAA. One patient in this population had no LAA. LAA size was significantly larger in patients with persistent AF than in those with paroxysmal AF (23.3 ± 4.2 mm vs. 20.0 ± 3.0 mm, p < 0.001) and in male patients than in female patients (22.4 ± 4.2 vs. 20.9 ± 3.7 mm, p = 0.03). LAA orifice dimension was significantly correlated with CHADS2 score, the left atrial volume (LAV), E/e′, and the left ventricular ejection fraction. Persistent AF, body mass index, and LAV were independently associated with LAA orifice dimension in multivariate analysis. Conclusion: This study demonstrated the distribution of LAA orifice dimension in the Japanese AF patients. This finding should be used as a reference to understand the racial characteristics of LAA size for the WATCHMAN procedure.
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JCS 2021 Guideline on the Clinical Application of Echocardiography
Ohte N., Ishizu T., Izumi C., Itoh H., Iwanaga S., Okura H., Otsuji Y., Sakata Y., Shibata T., Shinke T., Seo Y., Daimon M., Takeuchi M., Tanabe K., Nakatani S., Nii M., Nishigami K., Hozumi T., Yasukochi S., Yamada H., Yamamoto K., Izumo M., Inoue K., Iwano H., Okada A., Kataoka A., Kaji S., Kusunose K., Goda A., Takeda Y., Tanaka H., Dohi K., Hamaguchi H., Fukuta H., Yamada S., Watanabe N., Akaishi M., Akasaka T., Kimura T., Kosuge M., Masuyama T.
Circulation Journal 86 ( 12 ) 2045 - 2119 2022年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation Journal
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Prognostic impact of incident left ventricular systolic dysfunction after myocardial infarction 査読あり
Yoshioka G., Tanaka A., Watanabe N., Nishihira K., Natsuaki M., Kawaguchi A., Shibata Y., Node K.
Frontiers in Cardiovascular Medicine 9 1009691 2022年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Frontiers in Cardiovascular Medicine
Introduction: We sought to investigate the prognostic impact of incident left ventricular (LV) systolic dysfunction at the chronic phase of acute myocardial infarction (AMI). Materials and methods: Among 2,266 consecutive patients admitted for AMI, 1,330 patients with LV ejection fraction (LVEF) ≥ 40% during hospitalization who had LVEF data at 6 months after AMI were analyzed. Patients were divided into three subgroups based on LVEF at 6 months: reduced-LVEF (<40%), mid-range-LVEF (≥ 40% and < 50%) and preserved-LVEF (≥ 50%). Occurrence of a composite of hospitalization for heart failure or cardiovascular death after 6 months of AMI was the primary endpoint. The prognostic impact of LVEF at 6 months was assessed with a multivariate-adjusted Cox model. Results: Overall, the mean patient age was 67.5 ± 11.9 years, and LVEF during initial hospitalization was 59.4 ± 9.1%. The median (interquartile range) duration of follow-up was 3.0 (1.5–4.8) years, and the primary endpoint occurred in 35/1330 (2.6%) patients (13/69 [18.8%] in the reduced-LVEF, 9/265 [3.4%] in the mid-range-LVEF, and 13/996 [1.3%] in the preserved-LVEF category). The adjusted hazard ratio for the primary endpoint in the reduced-LVEF vs. mid-range-LVEF category and in the reduced-LVEF vs. preserved-LVEF category was 4.71 (95% confidence interval [CI], 1.83 to 12.13; p < 0.001) and 14.37 (95% CI, 5.38 to 38.36; p < 0.001), respectively. Conclusion: Incident LV systolic dysfunction at the chronic phase after AMI was significantly associated with long-term adverse outcomes. Even in AMI survivors without LV systolic dysfunction at the time of AMI, post-AMI reassessment and careful monitoring of LVEF are required to identify patients at risk.
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Honda Y., Watanabe N., Nishino S., Shibata Y.
Journal of Cardiology Cases 26 ( 3 ) 190 - 193 2022年9月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology Cases
A 57-year-old female presented to us with takotsubo cardiomyopathy. Echocardiogram revealed systolic anterior movement of the mitral valve (SAM) and severe mitral regurgitation (MR) with left ventricular (LV) dysfunction. After intensive medical treatment, SAM and MR almost disappeared along with the restoration of LV wall motion abnormality. We quantitatively analyzed three-dimensional mitral complex geometry at the acute phase and the recovery phase. At the initial examination when the transient SAM was observed, annulus diameters and area were significantly smaller, compared with the recovery phase. Excessive systolic movement of the annulus along with hyperdynamic LV basal wall may contribute to the transient SAM with severe MR. Learning objective: Recent studies have suggested systolic anterior movement of the mitral valve (SAM) causes acute mitral regurgitation in patients with takotsubo cardiomyopathy. However, the mechanism of transient SAM in Takotsubo cardiomyopathy remains unclear. This is the first report that assessed the unique geometric mechanisms of transient SAM in Takotsubo cardiomyopathy.
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Multiple asymptomatic coronary plaque ruptures and fissures in acute myocardial infarction. 査読あり
Gi T, Nishino S, Yamashita A, Watanabe N, Shibata Y, Asada Y.
Pathol Int. 72 ( 6 ) 355 - 357 2022年6月
記述言語：英語 掲載種別：研究論文（学術雑誌）
DOI： 10.1111/pin.13229.
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特集 心エコー計測/抽出のコツ,身につけたい考え方/進め方 Ⅱ 身につけたい考え方/進め方 3 病気を識る,病気を診る b. 僧帽弁狭窄症･僧帽弁逆流症(一次性) 査読あり
山村 善政, 渡邉 望
Heart View 25 ( 12 ) 122 - 129 2021年11月
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Furugen M., Watanabe N., Nishino S., Kimura T., Ashikaga K., Kuriyama N., Shibata Y.
Journal of Cardiology 78 ( 5 ) 423 - 430 2021年11月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology
Background: Previous studies have proposed that osteogenic and apoptotic processes of valve interstitial cells contribute to the mineralization and then calcification of the aortic valve. Osteoblast-like cells subsequently mediate calcification of the aortic valve as part of a highly regulated process analogous to skeletal bone formation. The objective of this study was to evaluate the pathogenesis of the sclerotic/calcific changes in the aortic valve from histological and biological findings, and investigate the role of osteoblasts in the calcified pathway of aortic stenosis. Methods: Preoperative echocardiography in 550 consecutive patients with osteoporotic hip fracture were retrospectively examined (475 females, mean 25th–75th, 89 [85–93] years). One hundred sixteen patients were under medical treatment with anti-osteoporosis drugs. We evaluated the prevalence and degree of degenerative changes in the aortic valve and examined the associations of bone turnover biomarkers N-terminal pro-peptide of type 1 collagen (P1NP) and serum tartrate-resistant acid phosphatase (TRACP-5b) with degenerative calcific changes in the aortic valve. Results: Of 550 patients, 112 patients (20.9%) showed no leaflet calcification; 296 (53.8%), 1 leaflet calcification; and 142 (25.8%), 2 ≥ leaflets calcification. Significant (peak velocity ≥ 3.0m/s) Aortic stenosis was found in 43 patients (7.8%). In patients who were not taking anti-osteoporotic drugs, P1NP was higher in the 2 ≥ leaflets calcification group than in the other groups (p < 0.01). TRACP-5b was not significantly different among the three groups (p = 0.15). Conclusions: Degenerative changes in the aortic valve were related to bone biomarker activation in osteoporotic hip fracture patients.
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Designer Exosomes: Smart Nano-Communication Tools for Translational Medicine. 査読あり
Harishkumar M, Radha M, Yuichi N, Muthukalianan GK, Kaoru O, Shiomori K, Sakai K, Nozomi W
Bioengineering (Basel, Switzerland) 8 ( 11 ) 158 2021年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：MDPI AG
<jats:p>Exosomes are the master transporters of genes, RNAs, microRNAs, proteins, and lipids. They have applications in major diseases, including cancer, cardiovascular diseases, neurological disorders, and diabetes mellitus. Delivery of the exosomes to recipient cells is governed by the functional heterogenicity of the tissues. Engineered exosomes are promising tools in tissue regeneration. In addition to their role as intracellular communication cargos, exosomes are increasingly primed as standard biomarkers in the progression of diseases, thereby solving the diagnostic dilemma. Futuristic empowerment of exosomes with OMICS strategy can undoubtedly be a bio-tool in translational medicine. This review discusses the advent transformation of exosomes in regenerative medicine and limitations that are caveats to broader applications in clinical use.</jats:p>
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Haruki Shinomiya, Hisakazu Kato, Yuki Kuramoto, Nozomi Watanabe, Toshihiro Tsuruda, Tadaaki Arimura, Yohei Miyashita, Yoshiki Miyasaka, Tomoji Mashimo, Ayako Takuwa, Daisuke Motook, Daisuke Okuzaki, Ken Matsuoka, Osamu Tsukamoto, Hideyuki Hakui,Noriaki Yamada,Jong-Kook Lee,Hidetaka Kioka,Masafumi Kitakaze,Seiji Takashima,Yasushi Sakata,Yoshihiro Asano
FASEB Journal 35 ( 11 ) e21994 2021年10月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：FASEB Journal
Arrhythmogenic cardiomyopathy (ACM) caused by TMEM43 p.S358L is a fully penetrant heart disease that results in impaired cardiac function or fatal arrhythmia. However, the molecular mechanism of ACM caused by the TMEM43 variant has not yet been fully elucidated. In this study, we generated knock-in (KI) rats harboring a Tmem43 p.S358L mutation and established induced pluripotent stem cells (iPSCs) from patients based on the identification of TMEM43 p.S358L variant from a family with ACM. The Tmem43-S358L KI rats exhibited ventricular arrhythmia and fibrotic myocardial replacement in the subepicardium, which recapitulated the human ACM phenotype. The four-transmembrane protein TMEM43 with the p.S358L variant (TMEM43S358L) was found to be modified by N-linked glycosylation in both KI rat cardiomyocytes and patient-specific iPSC-derived cardiomyocytes. TMEM43S358L glycosylation increased under the conditions of enhanced endoplasmic reticulum (ER) stress caused by pharmacological stimulation or age-dependent decline of the ER function. Intriguingly, the specific glycosylation of TMEM43S358L resulted from the altered membrane topology of TMEM43. Moreover, unlike TMEM43WT, which is mainly localized to the ER, TMEM43S358L accumulated at the nuclear envelope of cardiomyocytes with the increase in glycosylation. Finally, our comprehensive transcriptomic analysis demonstrated that the regional differences in gene expression patterns between the inner and outer layers observed in the wild type myocardium were partially diminished in the KI myocardium prior to exhibiting histological changes indicative of ACM. Altogether, these findings suggest that the aberrant accumulation of TMEM43S358L underlies the pathogenesis of ACM caused by TMEM43 p.S358L variant by affecting the transmural gene expression within the myocardium.
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Non-rheumatic giant left atrium: An illustrative case successfully treated by surgical intervention 査読あり
Honda Y., Watanabe N., Nishino S., Matsuura H., Nishimura M., Yano M., Kataoka H., Shibata Y.
Journal of Cardiology Cases 24 ( 2 ) 79 - 83 2021年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Cardiology Cases
A 45-year-old male presented to us with decompensated heart failure. He had been diagnosed as having atrial fibrillation when he was 31 years old. Transthoracic and transesophageal echocardiography revealed an excessive left atrial (LA) enlargement with left ventricular dysfunction and severe functional mitral regurgitation. There were no specific findings of rheumatic valve disease. He underwent surgical mitral valve replacement and LA volume reduction surgery after optimal medical therapy. Surgically-removed specimens of the LA and the anterior mitral leaflet were examined and there were no specific histopathological findings suggesting the specific etiology of the giant LA in this patient. The patient's condition significantly improved after the surgery without any cardiac events ever since. <Learning objective: Non-rheumatic giant left atrium (LA) is rare but can cause decompensated heart failure with various types of complications and hemodynamic problems. Mitral annular dilation and changes in the valve morphology often cause functional mitral regurgitation in giant LA, which adversely affect the hemodynamic condition. Valve surgery and surgical reduction of LA was effective in the present case.>
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Matsuura H., Watanabe N., Shibata Y., Asada Y.
Journal of Echocardiography 19 ( 2 ) 86 - 94 2021年6月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Echocardiography
Myocarditis is a fatal inflammatory disease of myocardium, diagnosed with clinical and histopathological findings by endomyocardial biopsy (EMB). Myocarditis has a variety of clinical presentations and a dynamic and sometimes rapid process of severity. Echocardiography plays an important role in the management of myocarditis because it has noninvasiveness and portability. Once acute myocarditis is suspected by an echocardiography, pathological information should be required as early as possible. In our cardiovascular center, emergency EMB suspecting myocarditis was performed in 19 cases (1.3%) among consecutive 1469 cases (70.1 ± 12.6 years old, male 67.5%) undergoing emergency coronary angiograms from April 2014 to September 2017. Hematoxylin–eosin stain of the biopsy specimens were prepared with microwave-accelerated histoprocessing within 3–5 hours after EMB for rapid pathological diagnosis of myocarditis. We reviewed the value of emergency echo-EMB combination leading to the early decision making of intensive care, corticosteroids and proper mechanical circulatory support prior to the possible sudden collapse in patients with myocarditis.
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ST-Elevation Myocardial Infarction With Cardiogenic Shock and Severe Acute Ischemic Mitral Regurgitation Rescued by Primary Coronary Intervention Under Hemodynamic Support With Impella. 査読あり
Koiwaya H, Watanabe N, Nishihira K, Goriki Y, Shibata Y
Circulation reports 3 ( 5 ) 304 - 305 2021年4月
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Nishihira K., Yoshioka G., Kuriyama N., Ogata K., Kimura T., Matsuura H., Furugen M., Koiwaya H., Watanabe N., Shibata Y.
European Heart Journal - Quality of Care and Clinical Outcomes 7 ( 2 ) 189 - 197 2021年4月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：European Heart Journal - Quality of Care and Clinical Outcomes
Aims: Frailty is characterized by reduced biological reserves and weakened resistance to stressors, and is common in older adults. This study evaluated the prognostic implications of frailty at hospitalization in elderly patients with acute myocardial infarction (AMI) who undergo percutaneous coronary intervention (PCI). Methods and results: We prospectively analysed 546 AMI patients aged ≥80 years undergoing PCI from 2009 to 2017. Frailty was classified based on impairment in walking (unassisted, assisted, and wheelchair/non-Ambulatory), cognition (normal, mildly impaired, moderately to severely impaired), and basic activities of daily living. Impairment in each domain was scored as 0, 1, or 2, and patients were categorized into the following three groups based on total score: no frailty (0), mild frailty (1-2), moderate-To-severe frailty (≥3). The median follow-up period was 589 days. Of the 546 patients, 27.8% were frail (mild or moderate-To-severe), and this proportion significantly increased to 35.5% at discharge (P < 0.001). Compared to non-frail patients, frail patients were older, less likely to be male, and had a higher rate of advanced Killip class. Major bleeding (no frailty, 9.6%; mild frailty, 16.9%; moderate-To-severe frailty, 31.8%; P < 0.001) and in-hospital mortality (no frailty, 8.4%; mild frailty, 15.4%; moderate-To-severe frailty, 27.3%; P < 0.001) increased as frailty worsened. After adjusting for confounders, frailty was independently associated with higher mid-Term all-cause mortality (hazard ratio, 1.81; 95% confidence interval, 1.23-2.65; P = 0.002). Conclusion: Frailty in AMI patients aged ≥80 years undergoing PCI was associated with major bleeding, in-hospital death, and mid-Term mortality.
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Designer Exosomes: Smart Nano-Communication Tools for Translational Medicine 査読あり 国際共著
Madhyastha H, Madhyastha R, Nakajima Y, Gothandam KM, Ohe K, Shiomori K and Watanabe N
Bioengineering 2021年
担当区分：最終著者 記述言語：英語 掲載種別：研究論文（学術雑誌）
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Prognostic impact of follow-up serum albumin after acute myocardial infarction 査読あり
Yoshioka G., Tanaka A., Nishihira K., Natsuaki M., Kawaguchi A., Watanabe N., Shibata Y., Node K.
ESC Heart Failure 8 ( 6 ) 5456 - 5465 2021年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：ESC Heart Failure
Aims: Previous studies have suggested that low serum albumin (LSA) at admission for acute myocardial infarction (AMI) is associated with adverse in-hospital outcomes. The aim of this study was to investigate whether LSA in the remote phase after AMI is prognostic for long-term outcomes. Methods and results: This was a single-centre, retrospective study of consecutive patients admitted for AMI from 2008 to 2016. Serum albumin concentrations were measured serially at admission and 1 year after discharge in Japanese patients. Occurrence of a composite of hospitalization for heart failure and cardiovascular death was the primary endpoint. The prognostic impact of remote LSA, defined as a serum albumin level < 3.8 g/dL at 1 year after discharge, was investigated with a multivariate-adjusted Cox model. Among 1424 subjects analysed, 289 (20.3%) had LSA at admission, and 165 (11.6%) had LSA at 1 year after discharge. During follow-up (median: 4.1 years), the primary endpoint occurred in 31/165 (18.8%) patients with remote LSA and 42/1259 (3.3%) patients without it [adjusted hazard ratio (aHR), 2.76; 95% confidence interval (CI), 1.32 to 5.72; P = 0.007]. The all-cause death rate was 29.7% (49/165) in patients with remote LSA and 4.3% (54/1259) in patients without it (aHR, 4.02; 95% CI, 2.36 to 6.87; P < 0.001). The prognostic impact of remote LSA was consistent across albumin status in the acute phase of AMI. Conclusions: Regardless of albumin status in the acute phase of AMI, LSA in the remote phase after AMI was significantly associated with long-term adverse outcomes.
DOI： 10.1002/ehf2.13640
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Retinoic acid attenuates nuclear factor kappaB mediated induction of NLRP3 inflammasome 査読あり
Purbasari B., Madhyastha R., Madhyastha H., Nurrahmah Q.I., Maruyama M., Nakajima Y., Kataoka H., Watanabe N.
Pharmacological Reports 74 ( 1 ) 189 - 203 2021年
担当区分：最終著者 記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Pharmacological Reports
Background: Acetylcholine (ACh), a neurotransmitter and a part of the cholinergic system, can modify immune responses. Expression of acetylcholine receptors (AChR) in immune cells, including macrophages, leads to modulation of their function. Inflammasomes are part of the innate immune system and have been linked to a variety of inflammatory diseases. The NLRP3/ASC/caspase-1/IL-1 axis has emerged as a critical signaling pathway in inflammation process initiation. The role of ACh in modulating inflammasomes in macrophages remains relatively under-explored. Methods: The effect of AChR agonist carbachol on inflammasome expression was investigated using murine and human macrophages. Cell lysates were assessed by western blot for protein analysis. Immunofluorescence studies were used to study the translocation of p65. The experiments were conducted in the presence of NF-ĸB inhibitor, AChR antagonists, and retinoic acid (RA) to study the role of NF-ĸB, ACh receptors, and RA, respectively. Results: We found that carbachol increased the expression of NLRP3 inflammasome (NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18). The treated cells also showed an increase in NF-ĸB activation. The effect of carbachol was diminished by NF-ĸB inhibitor and atropine, a mAChR antagonist. The addition of RA also significantly reduced the effect of carbachol on NLRP3 inflammasomes. Conclusions: Our current study suggests that carbachol induces NLRP3 inflammasome activation through mAChR and NF-ĸB, and that RA abolishes the inflammatory response. It reveals the potentials of co-administration of RA with cholinergic drugs to prevent inflammatory responses during cholinergic medications.
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Seo Y., Daimon M., Yamada H., Kagiyama N., Ohta M., Izumi C., Yamamoto K., Nakatani S., Sakata Y., Toide H., Akasaka K., Inoue K., Ohnishi T., Dohi K., Yoshimuta T., Watanabe N., Koitabashi T., Iino T., Komuro K., Kobayashi A., Hayashida A., Mizukami N., Hirata K., Wada Y., Kotani A., Takigiku K., Miyake M., Okaniwa H., Hirano Y., Murata M., Suzuki K.
Journal of Echocardiography 18 ( 4 ) 226 - 233 2020年12月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Echocardiography
Under the coronavirus disease 2019 (COVID-19) pandemic, the Japanese Society of Echocardiography (JSE) has been working to protect medical staff involved in echocardiographic examinations and to prevent secondary infections caused by the examinations since mid-March 2020. This review aims to describe the footprint of the JSE's responses, focusing on the 3 months in which the initial outbreak of COVID-19 pandemic occurred in Japan. We summarized the six parts as follows: (1) the initial actions for COVID-19 of JSE, (2) JSE’s actions for infection control-associated echocardiographic examinations, (3) statements from the American Society of Echocardiography during the COVID-19 pandemic and their Japanese translation by JSE, (4) making videos for explaining the practice of echocardiography during the COVID-19 pandemic, (5) attempts with the JSE members’ opinions by the communication platform and surveys, and (6) efforts of final statement during the initial spread of COVID-19. We look forward that this review will help daily practices associated with echocardiography under the COVID-19 pandemic and in the future event of an unknown infectious disease pandemic.
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JCS/JSCS/JATS/JSVS 2020 Guidelines on the Management of Valvular Heart Disease 査読あり
Izumi C., Eishi K., Ashihara K., Arita T., Otsuji Y., Kunihara T., Komiya T., Shibata T., Seo Y., Daimon M., Takanashi S., Tanaka H., Nakatani S., Ninami H., Nishi H., Hayashida K., Yaku H., Yamaguchi J., Yamamoto K., Watanabe H., Abe Y., Amaki M., Amano M., Obase K., Tabata M., Miura T., Miyake M., Murata M., Watanabe N., Akasaka T., Okita Y., Kimura T., Sawa Y., Yoshida K.
Circulation Journal 84 ( 11 ) 2037 - 2119 2020年10月
記述言語：日本語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation Journal
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Anatomical and physiological assessment of a symptomatic anomalous origin of the right coronary artery from the pulmonary artery by noninvasive imaging examinations. 査読あり
Nishino S, Watanabe N, Komatsu M, Yano M, Shibata Y
Journal of cardiology cases 22 ( 2 ) 72 - 76 2020年8月
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Nishihira K, Watanabe N, Kuriyama N, Shibata Y
European heart journal. Acute cardiovascular care 9 ( 5 ) 488 - 495 2020年8月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：European Heart Journal: Acute Cardiovascular Care
Background: With increases in life expectancy, percutaneous coronary intervention is being performed more often, even in elderly patients with acute myocardial infarction. However, the optimal management of nonagenarians with acute myocardial infarction is uncertain. This study sought to investigate clinical outcomes of nonagenarians who undergo percutaneous coronary intervention. Methods: Of 2640 consecutive patients with acute myocardial infarction hospitalised within 24 hours after symptom onset in 2009–2018, we prospectively analysed 96 nonagenarians (median age 92 years; interquartile range 91–94) who underwent percutaneous coronary intervention. Results: The median follow-up period was 375 days. Inhospital major bleeding (Bleeding Academic Research Consortium type 3 or 5) and inhospital death occurred in 15.6% and 17.7% of patients, respectively. The proportion of patients with frailty increased during hospitalisation, from 43.8% (mild frailty 37.5%; moderate to severe frailty 6.3%) at admission to 60.7% (mild frailty 46.8%; moderate to severe frailty 13.9%) at discharge (P < 0.01). The cumulative incidence of all-cause mortality was 22.2% at 180 days and 27.5% at 365 days. After adjusting for confounders, cardiogenic shock (hazard ratio (HR) 2.85; 95% confidence interval (CI) 1.07–7.64) and final thrombolysis in myocardial infarction flow grade less than 3 (HR 2.45; 95% CI 1.03–5.58) were associated with higher mid-term mortality and cardiac rehabilitation (HR 0.25; 95% CI, 0.13–0.50) was associated with lower mid-term mortality. Conclusions: The mid-term mortality of selected nonagenarians with acute myocardial infarction who undergo percutaneous coronary intervention is reasonable, but older patients have high rates of inhospital major bleeding and progression of frailty. This study provides physicians, patients and families with important information for therapeutic decision-making.
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Anomalous band in the left atrium: a rare embryologic remnant causing severe mitral regurgitation. 査読あり
Nishino S, Watanabe N, Yano M, Shibata Y
European heart journal. Case reports 4 ( 4 ) 1 - 2 2020年8月
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Lost in the Woods? Then We Need a Bird's-Eye View: Integrative Approach for the Doppler Assessment of Mitral Regurgitation. 査読あり
Watanabe N
Circulation. Cardiovascular imaging 13 ( 5 ) e010788 2020年5月
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Goriki Y., Tanaka A., Nishihira K., Kawaguchi A., Natsuaki M., Watanabe N., Ashikaga K., Kuriyama N., Shibata Y., Node K.
Journal of Clinical Medicine 9 ( 3 ) 2020年3月
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Journal of Clinical Medicine
In emergency clinical settings, it may be beneficial to use rapidly measured objective variables for the risk assessment for patient outcome. This study sought to develop an easy-to-measure and objective risk-score prediction model for in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI). A total of 1027 consecutive STEMI patients were recruited and divided into derivation (n = 669) and validation (n = 358) cohorts. A risk-score model was created based on the combination of blood test parameters obtained immediately after admission. In the derivation cohort, multivariate analysis showed that the following 5 variables were significantly associated with in-hospital death: estimated glomerular filtration rate <45 mL/min/1.73 m2, platelet count <15 × 104/µL, albumin ≤3.5 g/dL, high-sensitivity troponin I >1.6 ng/mL, and blood sugar ≥200 mg/dL. The risk score was weighted for those variables according to their odds ratios. An incremental change in the scores was significantly associated with elevated in-hospital mortality (p < 0.001). Receiver operating characteristic curve analysis showed adequate discrimination between patients with and without in-hospital death (derivation cohort: area under the curve (AUC) 0.853; validation cohort: AUC 0.879), and there was no significant difference in the AUC values between the laboratory-based and Global Registry of Acute Coronary Events (GRACE) score (p = 0.721). Thus, our laboratory-based model might be helpful in objectively and accurately predicting in-hospital mortality in STEMI patients.
DOI： 10.3390/jcm9030852
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Unique mechanism of mitral valve prolapse in atrial septal defect: Three-dimensional insights into mitral complex geometry using real-time transesophageal echocardiography. 査読あり
Furugen M, Watanabe N, Nishino S, Kimura T, Ashikaga K, Kuriyama N, Shibata Y
Echocardiography (Mount Kisco, N.Y.) 37 ( 3 ) 445 - 452 2020年3月
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Nishino S., Watanabe N., Gi T., Kuriyama N., Shibata Y., Asada Y.
Circulation: Cardiovascular Imaging 13 ( 12 ) e011396 2020年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：Circulation: Cardiovascular Imaging
Background: Recent animal studies have suggested that mitral valve (MV) leaflet remodeling can occur even without significant tethering force and that the postinfarct biological reaction would contribute to the histopathologic changes of the leaflet. We serially evaluated the MV remodeling in patients with anterior and inferior acute myocardial infarction (MI), by using 2-And 3-dimensional transthoracic echocardiography. Additional histopathologic examinations were performed to assess the leaflet pathology. Methods: Sixty consecutive first-onset acute MI (anterior MI, n=30; inferior MI, n=30) patients who underwent successful primary percutaneous coronary intervention were examined (1) before primary percutaneous coronary intervention, (2) at 6-month follow-up, and (3) at follow-up 1 year or later after onset. MV complex geometry including MV leaflet area and thickness was analyzed using dedicated software. Additional histopathologic study compared 18 valves harvested during surgery for ischemic mitral regurgitation (MR). Results: MV area and thickness incrementally increased during the follow-up period. MV leaflet area significantly increased (anterior MI: 5.59 [5.28-5.98] to 6.54 [6.20-7.26] cm2/m2, P<0.001; inferior MI: 5.60 [4.76-6.08] to 6.32 [5.90-6.90] cm2/m2, P<0.001), and leaflet thickness also increased (anterior MI: 1.09 [0.92-1.24] to 1.45 [1.28-1.60] mm/m2, P<0.001; inferior MI: 1.15 [1.03-1.25] to 1.44 [1.27-1.59] mm/m2, P<0.001); data represent onset versus ≥1 year. Larger annuls, larger tenting, and a reduced leaflet area/annular ratio with smaller coaptation index were observed in patients with persistent ischemic MR compared with those without significant ischemic MR. Histopathologic examinations revealed that MV thickness was significantly greater in chronic ischemic MR compared with acute ischemic MR (1432.6±490.5 versus 628.7±278.7 μm; P=0.001), with increased smooth muscle cells and fibrotic materials. Conclusions: MV leaflet remodeling progressed both in area and thickness after MI. This is the first clinical study to record the longitudinal course of MV leaflet remodeling by serial echocardiography.
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Hei S., Iwataki M., Jang J.Y., Kuwaki H., Fukuda S., Kim Y.J., Toki M., Onoue T., Hayashi A., Nishino S., Watanabe N., Hayashida A., Tsuda Y., Araki M., Nishimura Y., Song J.K., Yoshida K., Levine R.A., Otsuji Y.
International Heart Journal 61 ( 5 ) 970 - 978 2020年
記述言語：英語 掲載種別：研究論文（学術雑誌） 出版者・発行元：International Heart Journal
The mechanism of systolic annular expansion in mitral valve prolapse (MVP) is not clarified. Since annular expansion is systolic outward shift of MV leaflet/chorda tissue complex at superior and outer ends, annular expansion could be related to inward (superior) shift of the complex at another inferior and inner end of the papillary muscle (PM) tip and/or systolic lengthening of the tissue complex, especially MV leaflets. MV annulus systolic expansion, PMs’ systolic superior shift, and MV leaflets’ systolic lengthening were evaluated by echocardiography with a speckle tracking analysis in 25 normal subjects, 25 subjects with holo-systolic MVP and 20 subjects with late-systolic MVP. PMs’ superior shift, MV leaflets’ lengthening, MV annular area at the onset of systole and subsequent MV annulus expansion were significantly greater in late-systolic MVP than in holo-systolic MVP (4.6 ± 1.6 versus 1.5 ± 0.7 mm/m2, 2.5 ± 1.4 versus 0.6 ± 2.0 mm/m2, 6.8 ± 2.5 versus 5.7 ± 1.0 cm2/m2 and 1.6 ± 0.8 versus 0.1 ± 0.5 cm2/m2, P < 0.001, respectively). Multivariate analysis identified MV leaflets’ lengthening and PMs’ superior shift as independent factors associated with MV annular expansion. Conclusions: These results suggest that systolic MV annular expansion in MVP is related to abnormal MV leaflets’ lengthening and PMs’ superior shift.
DOI： 10.1536/ihj.20-236