著者
Shin-ichi Momomura Yoshihiko Saito Yoshio Yasumura Kazuhiro Yamamoto Yasushi Sakata Masao Daimon Koichiro Kinugawa Hiroshi Okamoto Naoki Dohi Issei Komuro
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-17-0532, (Released:2017-08-02)
参考文献数
10
被引用文献数
5 8

Background:TY-0201 (TY) is a transdermal formulation of bisoprolol that is the free base of bisoprolol fumarate (BO), a drug widely used to treat chronic heart failure (CHF). The objectives of this phase II study were to evaluate the efficacy and safety of TY when switching from oral BO to TY in patients with CHF whose drug therapy was optimized, and to determine the dose conversion rate of BO to TY.Methods and Results:The efficacy and safety of once daily TY patch use for 16 weeks was investigated in 40 patients with CHF who were stabilized with an optimized drug treatment, including BO, after switching from BO to TY at the dose conversion rate of 5:8. The pre-switch left ventricular ejection fraction was 50.13±11.09% (mean±SD). The post-switch value was 50.87±10.79% after 16 weeks, which was not significantly different, with similar results for other efficacy and safety parameters. The 16-week study was continued for all patients without changing doses after switching to TY. No cardiovascular deaths, hospitalizations for worsening HF, or significant safety concerns were observed.Conclusions:Efficacy was maintained without significant safety concerns in patients with CHF who were stabilized with BO treatment after switching to TY, suggesting the appropriateness of the dose conversion rate.
著者
Shinobu Sugihara Ichiro Hisatome Masanari Kuwabara Koichiro Niwa Nani Maharani Masahiko Kato Kazuhide Ogino Toshihiro Hamada Haruaki Ninomiya Yukihito Higashi Kimiyoshi Ichida Kazuhiro Yamamoto
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.79, no.5, pp.1125-1132, 2015-04-24 (Released:2015-04-24)
参考文献数
41
被引用文献数
24 82

Background:Uric acid (UA) serves as an antioxidant in vascular endothelial cells. UA transporter 1 (URAT1) encoded by SLC22A12 is expressed in the kidney and vessels and its loss of function causes hypouricemia. The purpose of this study was to examine whether there is any endothelial dysfunction in patients with hypouricemia.Methods and Results:Twenty-six patients with hypouricemia (<2.5 mg/dl) and 13 healthy control subjects were enrolled. Endothelial function was evaluated using flow-mediated dilation (FMD). mRNA of UA transporters expressed in cultured human umbilical endothelial cells (HUVEC) was detected on RT-PCR. There was a positive correlation between FMD and serum UA in the hypouricemia group. URAT1 loss-of-function mutations were found in the genome of 21 of 26 patients with hypouricemia, and not in the other 5. In the hypouricemia groups, serum UA in homozygous and compound heterozygous patients was significantly lower than in other groups, suggesting that severity of URAT1 dysfunction may influence the severity of hypouricemia. Thirteen of 16 hypouricemia subjects with homozygous and compound heterozygote mutations had SUA <0.8 mg/dl and their FMD was lower than in other groups. HUVEC do not express mRNA of URAT1, suggesting the null role of URAT1 in endothelial function.Conclusions:Depletion of UA due to SLC22A12/URAT1 loss-of-function mutations causes endothelial dysfunction in hypouricemia patients. (Circ J 2015; 79: 1125–1132)
著者
Hiroyuki Tsutsui Shin-ichi Momomura Yoshihiko Saito Hiroshi Ito Kazuhiro Yamamoto Tomomi Ohishi Naoko Okino Toshihito Kitamura Weinong Guo
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.82, no.10, pp.2575-2583, 2018-09-25 (Released:2018-09-25)
参考文献数
17
被引用文献数
1 15

Background: The objective of the present analyses was to describe the baseline characteristics and treatment of the Japanese patients with HFrEF in THE PARALLEL-HF study. Methods and Results: Key demographic, clinical and laboratory findings, along with treatment, were reported and compared with patients enrolled in the PARADIGM-HF trial and other contemporary randomized clinical trials and registries of Japanese patients with HFrEF. In addition, the MAGGIC and EMPHASIS-HF risk scores were calculated. A total of 225 Japanese patients were randomized in PARALLEL-HF with a mean age of 67.9 years and the majority of the patients being male (85.8%) and in NYHA Class II (93.8%). Key baseline characteristics in PARALLEL-HF were generally comparable with PARADIGM-HF, and other contemporary clinical trials and registries of Japanese HFrEF patients. Patients enrolled in PARALLEL-HF were well treated with conventional evidence-based therapy at baseline (angiotensin-converting enzyme inhibitor inhibitor/angiotensin receptor blocker, 62.7%/37.3%; β-blockers, 94.7%; mineralocorticoid receptor antagonist, 59.1%). Despite the evidence-based treatment and most patients being in NYHA Class II, these patients had a low LVEF (mean 28.1%) and were at high risk of cardiovascular mortality and morbidity as assessed by the MAGGIC and EMPHASIS-HF risk scores. Conclusions: Overall, the patients in PARALLEL-HF were largely representative of contemporary ambulatory patients with HFrEF who are well treated with evidence-based therapies. PARALLEL-HF will determine whether sacubitril/valsartan provides similar improvements in clinical outcomes in Japanese HFrEF patients as observed in the PARADIGM-HF study.
著者
Hiroyuki Tsutsui Shin-ichi Momomura Yoshihiko Saito Hiroshi Ito Kazuhiro Yamamoto Tomomi Ohishi Naoko Okino Toshihito Kitamura Weinong Guo
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-17-1424, (Released:2018-07-26)
参考文献数
17
被引用文献数
15

Background:The objective of the present analyses was to describe the baseline characteristics and treatment of the Japanese patients with HFrEF in THE PARALLEL-HF study.Methods and Results:Key demographic, clinical and laboratory findings, along with treatment, were reported and compared with patients enrolled in the PARADIGM-HF trial and other contemporary randomized clinical trials and registries of Japanese patients with HFrEF. In addition, the MAGGIC and EMPHASIS-HF risk scores were calculated. A total of 225 Japanese patients were randomized in PARALLEL-HF with a mean age of 67.9 years and the majority of the patients being male (85.8%) and in NYHA Class II (93.8%). Key baseline characteristics in PARALLEL-HF were generally comparable with PARADIGM-HF, and other contemporary clinical trials and registries of Japanese HFrEF patients. Patients enrolled in PARALLEL-HF were well treated with conventional evidence-based therapy at baseline (angiotensin-converting enzyme inhibitor inhibitor/angiotensin receptor blocker, 62.7%/37.3%; β-blockers, 94.7%; mineralocorticoid receptor antagonist, 59.1%). Despite the evidence-based treatment and most patients being in NYHA Class II, these patients had a low LVEF (mean 28.1%) and were at high risk of cardiovascular mortality and morbidity as assessed by the MAGGIC and EMPHASIS-HF risk scores.Conclusions:Overall, the patients in PARALLEL-HF were largely representative of contemporary ambulatory patients with HFrEF who are well treated with evidence-based therapies. PARALLEL-HF will determine whether sacubitril/valsartan provides similar improvements in clinical outcomes in Japanese HFrEF patients as observed in the PARADIGM-HF study.
著者
Shota Fukuda Hiroyuki Watanabe Masao Daimon Yukio Abe Akihiro Hirashiki Kumiko Hirata Hiroshi Ito Masumi Iwai-Takano Katsuomi Iwakura Chisato Izumi Takayuki Hidaka Toshinori Yuasa Kazuya Murata Satoshi Nakatani Kazuaki Negishi Kazuhiro Nishigami Tomoko Nishikage Takahiro Ota Akihiro Hayashida Konomi Sakata Nobuhiro Tanaka Satoshi Yamada Kazuhiro Yamamoto Junichi Yoshikawa
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.76, no.5, pp.1177-1181, 2012 (Released:2012-04-25)
参考文献数
27
被引用文献数
27 67

Background: The recently developed real-time 3-dimensional echocardiography (RT3DE) is a promising imaging method to quantify cardiac chamber volumes and their functions in clinical practice. However, normal reference values of RT3DE parameters have not been fully investigated in a large, healthy Japanese population. Methods and Results: This study consisted of 410 healthy subjects aged from 20 to 69 years who had a RT3DE at one of the 23 collaborating institutions. All subjects had no history of cardiac disease and no risk factors. The mean values in men and women were as follows: 50±12ml/m2 and 46±9ml/m2 for left ventricular (LV) end-diastolic volume index, 19±5ml/m2 and 17±4ml/m2 for end-systolic volume index, 61±4% and 63±4% for ejection fraction, 64±12g/m2 and 56±11g/m2 for mass index, 23±6ml/m2 and 24±6ml/m2 for left atrial (LA) maximum volume index, 10±3ml/m2 and 10±3ml/m2 for minimum volume index, and 58±6% and 58±6% for percent volume change. LV sizes decreased with age, whereas LV mass index did not change. LA sizes slightly increased with age. Conclusions: This multicenter investigation determined normal reference values for LV and LA sizes, and their functional parameters on RT3DE in a large, healthy Japanese population. The results of the present study support the use of RT3DE for the diagnosis and management of cardiovascular disease. (Circ J 2012; 76: 1177-1181)
著者
Toshiaki Mano Kazuhiro Yamamoto
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-16-0368, (Released:2016-05-06)
参考文献数
22
被引用文献数
1

The 65thAnnual Scientific Sessions of the American College of Cardiology (ACC) were held at McCormick Place, Chicago, from April 2–4, 2016. The ACC Scientific Sessions are one of the 2 major scientific cardiology meetings in the USA and one of the major scientific meetings of cardiology in the world. It had an attendance of 18,769 and over 2,000 oral and poster abstracts, including 8 late-breaking clinical trials. This report presents the key presentations and the highlights from the ACC Scientific Sessions 2016 in Chicago.
著者
Shinobu Sugihara Ichiro Hisatome Masanari Kuwabara Koichiro Niwa Nani Maharani Masahiko Kato Kazuhide Ogino Toshihiro Hamada Haruaki Ninomiya Yukihito Higashi Kimiyoshi Ichida Kazuhiro Yamamoto
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-14-1267, (Released:2015-02-23)
参考文献数
41
被引用文献数
10 82

Background:Uric acid (UA) serves as an antioxidant in vascular endothelial cells. UA transporter 1 (URAT1) encoded by SLC22A12 is expressed in the kidney and vessels and its loss of function causes hypouricemia. The purpose of this study was to examine whether there is any endothelial dysfunction in patients with hypouricemia.Methods and Results:Twenty-six patients with hypouricemia (<2.5 mg/dl) and 13 healthy control subjects were enrolled. Endothelial function was evaluated using flow-mediated dilation (FMD). mRNA of UA transporters expressed in cultured human umbilical endothelial cells (HUVEC) was detected on RT-PCR. There was a positive correlation between FMD and serum UA in the hypouricemia group. URAT1 loss-of-function mutations were found in the genome of 21 of 26 patients with hypouricemia, and not in the other 5. In the hypouricemia groups, serum UA in homozygous and compound heterozygous patients was significantly lower than in other groups, suggesting that severity of URAT1 dysfunction may influence the severity of hypouricemia. Thirteen of 16 hypouricemia subjects with homozygous and compound heterozygote mutations had SUA <0.8 mg/dl and their FMD was lower than in other groups. HUVEC do not express mRNA of URAT1, suggesting the null role of URAT1 in endothelial function.Conclusions:Depletion of UA due to SLC22A12/URAT1 loss-of-function mutations causes endothelial dysfunction in hypouricemia patients.
著者
Hiroshi Fujii Yu Ikeuchi Yasutaka Kurata Nobuhito Ikeda Udin Bahrudin Peili Li Yuji Nakayama Ryo Endo Akira Hasegawa Kumi Morikawa Junichiro Miake Akio Yoshida Kyoko Hidaka Takayuki Morisaki Haruaki Ninomiya Yasuaki Shirayoshi Kazuhiro Yamamoto Ichiro Hisatome
出版者
日本循環器学会
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-12-0126, (Released:2012-09-04)
参考文献数
27
被引用文献数
3 2

Background: The prion protein (PrP) has been reported to serve as a surface maker for isolation of cardiomyogenic progenitors from murine embryonic stem (ES) cells. Although PrP-positive cells exhibited automaticity, their electrophysiological characteristics remain unresolved. The aim of the present study was therefore to investigate the electrophysiological properties of PrP-positive cells in comparison with those of HCN4p-or Nkx2.5-positive cells. Methods and Results: Differentiation of AB1, HCN5p-EGFP and hcgp7 ES cells into cardiac progenitors was induced by embryoid body (EB) formation. EBs were dissociated and cells expressing PrP, HCN4-EGFP and/or Nkx2.5-GFP were collected via flow cytometry. Sorted cells were subjected to reverse transcriptase-polymerase chain reaction, immunostaining and patch-clamp experiments. PrP-positive cells expressed mRNA of undifferentiation markers, first and second heart field markers, and cardiac-specific genes and ion channels, indicating their commitment to cardiomyogenic progenitors. PrP-positive cells with automaticity showed positive and negative chronotropic responses to isoproterenol and carbamylcholine, respectively. Hyperpolarization-activated cation current (If) was barely detectable, whereas Na+ and L-type Ca2+ channel currents were frequently observed. Their spontaneous activity was slowed by inhibition of sarcoplasmic reticulum Ca2+ uptake and release but not by blocking If. The maximum diastolic potential of their spontaneous firings was more depolarized than that of Nkx2.5-GFP-positive cells. Conclusions: PrP-positive cells contained cardiac progenitors that separated from the lineage of sinoatrial node cells. PrP can be used as a marker to enrich nascent cardiac progenitors.