著者

Jiro Sakamoto Yugo Yamashita Takeshi Morimoto Hidewo Amano Toru Takase Seiichi Hiramori Kitae Kim Maki Oi Masaharu Akao Yohei Kobayashi Mamoru Toyofuku Toshiaki Izumi Tomohisa Tada Po-Min Chen Koichiro Murata Yoshiaki Tsuyuki Syunsuke Saga Yuji Nishimoto Tomoki Sasa Minako Kinoshita Kiyonori Togi Hiroshi Mabuchi Kensuke Takabayashi Yusuke Yoshikawa Hiroki Shiomi Takao Kato Takeru Makiyama Koh Ono Toshihiro Tamura Yoshihisa Nakagawa Takeshi Kimura on behalf of the COMMAND VTE Registry Investigators

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-19-0515, (Released:2019-09-20)

参考文献数

28

被引用文献数

5 57

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Background:There is a paucity of data on the management and prognosis of cancer-associated venous thromboembolism (VTE), leading to uncertainty about optimal management strategies.Methods and Results:The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive acute symptomatic VTE patients in Japan between 2010 and 2014. We divided the entire cohort into 3 groups: active cancer (n=695, 23%), history of cancer (n=243, 8%), and no history of cancer (n=2089, 69%). The rate of anticoagulation discontinuation was higher in patients with active cancer (43.5%, 27.0%, and 27.0%, respectively, at 1 year, P<0.001). The cumulative 5-year incidences of recurrent VTE, major bleeding, and all-cause death were higher in patients with active cancer (recurrent VTE: 17.7%, 10.2%, and 8.6%, P<0.001; major bleeding: 26.6%, 8.8%, and 9.3%, P<0.001; all-cause death: 73.1%, 28.6%, 14.6%, P<0.001). Among the 4 groups classified according to active cancer status, the cumulative 1-year incidence of recurrent VTE was higher in the metastasis group (terminal stage group: 6.4%, metastasis group: 22.1%, under chemotherapy group: 10.8%, and other group: 5.8%, P<0.001).Conclusions:In a current real-world VTE registry, patients with active cancer had higher risk for VTE recurrence, bleeding, and death, with variations according to cancer status, than patients without active cancer. Anticoagulation therapy was frequently discontinued prematurely in patients with active cancer in discordance with current guideline recommendations.

著者

Megumi Fukuyama Minoru Horie Koichi Kato Hisaaki Aoki Shuhei Fujita Yoko Yoshida Hisanori Sakazaki Takako Toda Michihiko Ueno Gaku Izumi Nobuo Momoi Jun Muneuchi Takeru Makiyama Yoshihisa Nakagawa Seiko Ohno

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-23-0195, (Released:2023-06-28)

参考文献数

38

被引用文献数

1

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Background: Cardiac calmodulinopathy, characterized by a life-threatening arrhythmia and sudden death in the young, is extremely rare and caused by genes encoding calmodulin, namely calmodulin 1 (CALM1), CALM2, and CALM3.Methods and Results: We screened 195 symptomatic children (age 0–12 years) who were suspected of inherited arrhythmias for 48 candidate genes, using a next-generation sequencer. Ten probands were identified as carrying variants in any of CALM1–3 (5%; median age 5 years), who were initially diagnosed with long QT syndrome (LQTS; n=5), catecholaminergic polymorphic ventricular tachycardia (CPVT; n=3), and overlap syndrome (n=2). Two probands harbored a CALM1 variant and 8 probands harbored 6 CALM2 variants. There were 4 clinical phenotypes: (1) documented lethal arrhythmic events (LAEs): 4 carriers of N98S in CALM1 or CALM2; (2) suspected LAEs: CALM2 p.D96G and D132G carriers experienced syncope and transient cardiopulmonary arrest under emotional stimulation; (3) critical cardiac complication: CALM2 p.D96V and p.E141K carriers showed severe cardiac dysfunction with QTc prolongation; and (4) neurological and developmental disorders: 2 carriers of CALM2 p.E46K showed cardiac phenotypes of CPVT. Beta-blocker therapy was effective in all cases except cardiac dysfunction, especially in combination with flecainide (CPVT-like phenotype) and mexiletine (LQTS-like).Conclusions: Calmodulinopathy patients presented severe cardiac features, and their onset of LAEs was earlier in life, requiring diagnosis and treatment at the earliest age possible.

著者

Katsushige Ono Yu-ki Iwasaki Masaharu Akao Takanori Ikeda Kuniaki Ishii Yasuya Inden Kengo Kusano Yoshinori Kobayashi Yukihiro Koretsune Tetsuo Sasano Naokata Sumitomo Naohiko Takahashi Shinichi Niwano Nobuhisa Hagiwara Ichiro Hisatome Tetsushi Furukawa Haruo Honjo Toru Maruyama Yuji Murakawa Masahiro Yasaka Eiichi Watanabe Takeshi Aiba Mari Amino Hideki Itoh Hisashi Ogawa Yasuo Okumura Chizuko Aoki-Kamiya Jun Kishihara Eitaro Kodani Takashi Komatsu Yusuke Sakamoto Kazuhiro Satomi Tsuyoshi Shiga Tetsuji Shinohara Atsushi Suzuki Shinya Suzuki Yukio Sekiguchi Satoshi Nagase Noriyuki Hayami Masahide Harada Tadashi Fujino Takeru Makiyama Mitsunori Maruyama Junichiro Miake Shota Muraji Hiroshige Murata Norishige Morita Hisashi Yokoshiki Koichiro Yoshioka Kenji Yodogawa Hiroshi Inoue Ken Okumura Takeshi Kimura Hiroyuki Tsutsui Wataru Shimizu on behalf of the Japanese Circulation Society and Japanese Heart Rhythm Society Joint Working Group

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-20-1212, (Released:2022-03-11)

参考文献数

998

被引用文献数

44

著者

Koh Ono Satoshi Shizuta Erika Yamamoto Naritatsu Saito Neiko Ozasa Takao Kato Eri Kato Takahiro Horie Junichi Tazaki Hiroki Shiomi Shin Watanabe Hirotoshi Watanabe Yugo Yamashita Yusuke Yoshikawa Hideyuki Kinoshita Takeru Makiyama Yoshinori Yoshida Noboru Ashida Yasuaki Nakagawa Yasuhiro Nakashima Osamu Baba Hirohiko Kohjitani Masahiro Kimura Hideaki Inazumi Takashi Yoshizawa Akihiro Komasa Takeshi Kimura

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-21-0041, (Released:2021-01-30)

参考文献数

10

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Due to the COVID-19 pandemic, the 84thAnnual Meeting of the Japanese Circulation Society (JCS) was held in a web-based format for the first time in its history as “The Week for JCS 2020” from Monday, July 27 to Sunday, August 2, 2020. All sessions, including general abstracts, were streamed live or on-demand. The main theme of the meeting was “Change Practice!” and the aim was to organize the latest findings in the field of cardiovascular medicine and discuss how to change practice. The total number of registered attendees was over 16,800, far exceeding our expectations, and many of the sessions were viewed by far more people than at conventional face-to-face scientific meetings. At this conference, the power of online information dissemination was fully demonstrated, and the evolution of online academic meetings will be a direction that cannot be reversed in the future. The meeting was completed with great success, and we express our heartfelt gratitude to all affiliates for their enormous amount of work, cooperation, and support.

著者

Mari Ichikawa Takeshi Aiba Seiko Ohno Daichi Shigemizu Junichi Ozawa Keiko Sonoda Megumi Fukuyama Hideki Itoh Yoshihiro Miyamoto Tatsuhiko Tsunoda Takeru Makiyama Toshihiro Tanaka Wataru Shimizu Minoru Horie

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-16-0486, (Released:2016-10-25)

参考文献数

33

被引用文献数

1 17

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Background:Mutations inANK2have been reported to cause various arrhythmia phenotypes. The prevalence ofANK2mutation carriers in inherited primary arrhythmia syndrome (IPAS), however, remains unknown in Japanese. Using a next-generation sequencer, we aimed to identifyANK2mutations in our cohort of IPAS patients, in whom conventional Sanger sequencing failed to identify pathogenic mutations in major causative genes, and to assess the clinical characteristics ofANK2mutation carriers.Methods and Results:We screened 535 probands with IPAS and analyzed 46 genes including wholeANK2exons using a bench-top NGS (MiSeq, Illumina) or performed whole-exome-sequencing using HiSeq2000 (Illumina). As a result, 12 of 535 probands (2.2%, aged 0–61 years, 5 males) were found to carry 7 different heterozygousANK2mutations.ANK2-W1535R was identified in 5 LQTS patients and 1 symptomatic BrS and was predicted as damaging by multiple prediction software. In total, as to phenotype, there were 8 LQTS, 2 BrS, 1 IVF, and 1 SSS/AF. Surprisingly, 4/8 LQTS patients had the acquired type of LQTS (aLQTS) and suffered torsades de pointes. A total of 7 of 12 patients had documented malignant ventricular tachyarrhythmias.Conclusions:VariousANK2mutations are associated with a wide range of phenotypes, including aLQTS, especially with ventricular fibrillation, representing “ankyrin-B” syndrome.

著者

Yuji Nishimoto Yugo Yamashita Kitae Kim Takeshi Morimoto Syunsuke Saga Hidewo Amano Toru Takase Seiichi Hiramori Maki Oi Masaharu Akao Yohei Kobayashi Mamoru Toyofuku Toshiaki Izumi Tomohisa Tada Po-Min Chen Koichiro Murata Yoshiaki Tsuyuki Tomoki Sasa Jiro Sakamoto Minako Kinoshita Kiyonori Togi Hiroshi Mabuchi Kensuke Takabayashi Yusuke Yoshikawa Hiroki Shiomi Takao Kato Takeru Makiyama Koh Ono Yukihito Sato Takeshi Kimura on behalf of the COMMAND VTE Registry Investigators

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.84, no.11, pp.2006-2014, 2020-10-23 (Released:2020-10-23)

参考文献数

33

被引用文献数

21

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Background:Patients with cancer-associated venous thromboembolism (VTE) are at high risk for recurrent VTE and are recommended to receive prolonged anticoagulation therapy if they are at a low risk for bleeding. However, there are no established risk factors for bleeding during anticoagulation therapy.Methods and Results:The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3,027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 592 cancer-associated VTE patients with anticoagulation therapy. We constructed a multivariable Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the potential risk factors for major bleeding. During a median follow-up period of 199 days, major bleeding occurred in 72 patients. The cumulative incidence of major bleeding was 5.8% at 3 months, 13.8% at 1 year, 17.5% at 2 years, and 28.1% at 5 years. The most frequent major bleeding site was gastrointestinal tract (47%). Terminal cancer (adjusted HR, 4.17; 95% CI, 2.22–7.85, P<0.001), chronic kidney disease (adjusted HR, 1.89; 95% CI 1.06–3.37, P=0.031), and gastrointestinal cancer (adjusted HR, 1.78; 95% CI, 1.04–3.04, P=0.037) were independently associated with an increased risk of major bleeding.Conclusions:Major bleeding events were common during anticoagulation therapy in real-world cancer-associated VTE patients. Terminal cancer, chronic kidney disease, and gastrointestinal cancer were the independent risk factors for major bleeding.

著者

Keiichiro Yamane Yoshihiro Kato Junichi Tazaki Tomohisa Tada Takeru Makiyama Masao Imai Toshikazu Jinnai Tomoyuki Ikeda Ryutaro Shirakawa Takeshi Kimura Hisanori Horiuchi

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

vol.19, no.6, pp.559-569, 2012 (Released:2012-06-28)

参考文献数

30

被引用文献数

23 23

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Aim: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is essential after percutaneous coronary intervention (PCI). Clopidogrel is a prodrug and changed into active metabolite by cytochrome p450 enzymes (CYPs), especially CYP2C19. Proton pump inhibitors (PPIs) are used for the prevention of aspirin-induced gastrointestinal bleeding. PPIs are also metabolized by CYP2C19, although the degree of its contribution is dependent on the kind of PPI. Omeprazole, a PPI, has been reported to weaken the antiplatelet effects of clopidogrel. Famotidine, a histamine receptor type 2 (H2) blocker, could also be an alternative to PPIs. The aim of this study was to evaluate the effects of PPIs and an H2 blocker on the antiplatelet function of clopidogrel.Methods: Patients receiving DAPT due to prior PCI, who took either omeprazole or rabeprazole, were enrolled (n=25). The initial PPI was changed to the other PPI as a crossover study. In another study, patients undergoing DAPT without taking PPIs or H2 blockers were enrolled (n=30) and famotidine was added.Results: Platelet aggregability when taking omeprazole was higher than when taking rabeprazole, evaluated by an optical aggregometer using collagen as a stimulus (p=0.0051) and by the VerifyNow P2Y12 assay (p=0.0060). Platelet aggregability when taking rabeprazole was comparable to that in control patients (n=15). Concomitant use of famotidine had no effect.Conclusion: Omeprazole significantly reduced the antiplatelet effect of clopidogrel and this effect on clopidogrel was stronger than that of rabeprazole. Concomitant use of famotidine had no effect on the antiplatelet effect of clopidogrel.

著者

Mamoru Hayano Takeru Makiyama Tsukasa Kamakura Hiroshi Watanabe Kenichi Sasaki Shunsuke Funakoshi Yimin Wuriyanghai Suguru Nishiuchi Takeshi Harita Yuta Yamamoto Hirohiko Kohjitani Sayako Hirose Fumika Yokoi Jiarong Chen Osamu Baba Takahiro Horie Kazuhisa Chonabayashi Seiko Ohno Futoshi Toyoda Yoshinori Yoshida Koh Ono Minoru Horie Takeshi Kimura

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-17-0064, (Released:2017-06-20)

参考文献数

38

被引用文献数

23

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Background:TheSCN5Agene encodes the α subunit of the cardiac voltage-gated sodium channel, NaV1.5. The missense mutation, D1275N, has been associated with a range of unusual phenotypes associated with reduced NaV1.5 function, including cardiac conduction disease and dilated cardiomyopathy. Curiously, the reported biophysical properties ofSCN5A-D1275N channels vary with experimental system.Methods and Results:First, using a human embryonic kidney (HEK) 293 cell-based heterologous expression system, theSCN5A-D1275N channels showed similar maximum sodium conductance but a significantly depolarizing shift of activation gate (+10 mV) compared to wild type. Second, we generated human-induced pluripotent stem cells (hiPSCs) from a 24-year-old female who carried heterozygousSCN5A-D1275N and analyzed the differentiated cardiomyocytes (CMs). AlthoughSCN5Atranscript levels were equivalent between D1275N and control hiPSC-CMs, both the total amount of NaV1.5 and the membrane fractions were reduced approximately half in the D1275N cells, which were rescued by the proteasome inhibitor MG132 treatment. Electrophysiological assays revealed that maximum sodium conductance was reduced to approximately half of that in control hiPSC-CMs in the D1275N cells, and maximum upstroke velocity of action potential was lower in D1275N, which was consistent with the reduced protein level of NaV1.5.Conclusions:This study successfully demonstrated diminished sodium currents resulting from lower NaV1.5 protein levels, which is dependent on proteasomal degradation, using a hiPSC-based model forSCN5A-D1275N-related sodium channelopathy.

著者

Tsukasa Kamakura Takeru Makiyama Kenichi Sasaki Yoshinori Yoshida Yimin Wuriyanghai Jiarong Chen Tetsuhisa Hattori Seiko Ohno Toru Kita Minoru Horie Shinya Yamanaka Takeshi Kimura

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-12-0987, (Released:2013-02-09)

参考文献数

34

被引用文献数

28 221

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Background: In the short- to mid-term, cardiomyocytes generated from human-induced pluripotent stem cells (hiPSC-CMs) have been reported to be less mature than those of adult hearts. However, the maturation process in a long-term culture remains unknown. Methods and Results: A hiPSC clone generated from a healthy control was differentiated into CMs through embryoid body (EB) formation. The ultrastructural characteristics and gene expressions of spontaneously contracting EBs were analyzed through 1-year of culture after cardiac differentiation was initiated. The 14-day-old EBs contained a low number of myofibrils, which lacked alignment, and immature high-density Z-bands lacking A-, H-, I-, and M-bands. Through the long-term culture up to 180 days, the myofibrils became more tightly packed and formed parallel arrays accompanied by the appearance of mature Z-, A-, H-, and I-bands, but not M-bands. Notably, M-bands were finally detected in 360-day-old EBs. The expression levels of the M-band-specific genes in hiPSC-CMs remained lower in comparison with those in the adult heart. Immunocytochemistry indicated increasing number of MLC2v-positive/MLC2a-negative cells with decreasing number of MLC2v/MLC2a double-positive cells, indicating maturing of ventricular-type CMs. Conclusions: The structural maturation process of hiPSC-CMs through 1-year of culture revealed ultrastructural sarcomeric changes accompanied by delayed formation of M-bands. Our study provides new insight into the maturation process of hiPSC-CMs.