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

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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

Chitose Ishikawa Takayoshi Tsutamoto Masanori Fujii Hiroshi Sakai Toshinari Tanaka Minoru Horie

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.70, no.7, pp.857-863, 2006 (Released:2006-06-25)

参考文献数

31

被引用文献数

36 50

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Background The prognostic role of serum C-reactive protein (CRP) in chronic heart failure (CHF) patients, especially those with nonischemic dilated cardiomyopathy (DCM), remains unknown. In the present study, whether CRP provides prognostic information in DCM patients was evaluated. Methods and Results Neurohumoral factors and hemodynamics in 84 consecutive DCM patients were measured and these patients were followed up for a mean period of 42 months. During the follow-up period, 23 patients developed cardiac events and 18 patients died of cardiac causes. Using stepwise multivariate Cox proportional hazards regression analyses, log brain natriuretic peptide (BNP) (p=0.007) and high-sensitivity CRP (hsCRP) >1 mg/L (p=0.008) were significant independent predictors of cardiac events. The patients were stratified into 4 groups based on the normal serum concentration of hsCRP (1 mg/L) and median plasma concentration of BNP (110 pg/ml). Survival rates were significantly higher in patients with hsCRP <1 mg/L and BNP <110 pg/ml. The hazard ratio of patients with BNP >110 pg/ml and hsCRP >1 mg/L was 15.8 (95% confidence interval, 1.9-127.2) compared with those with BNP <110 pg/ml and hsCRP <1 mg/L for cardiac death. Conclusions Serum hsCRP level is an independent prognostic predictor in patients with DCM and the combination of hsCRP and BNP may be useful for the management of CHF patients with DCM. (Circ J 2006; 70: 857 - 863)

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 15

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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

Masao Yoshinaga Yumiko Ninomiya Yuji Tanaka Megumi Fukuyama Koichi Kato Seiko Ohno Minoru Horie Hiromitsu Ogata

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-23-0409, (Released:2023-12-01)

参考文献数

32

被引用文献数

1

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Background: This study was performed to clarify the clinical findings of pediatric patients diagnosed with long QT syndrome (LQTS) through electrocardiographic screening programs and to predict their outcome using Holter electrocardiographic approaches.Methods and Results: This retrospective study included pediatric patients with a Schwartz score of ≥3.5 who visited the National Hospital Organization Kagoshima Medical Center between April 2005 and March 2019. Resting 12-lead and Holter electrocardiograms were recorded at every visit. The maximum resting QTc and maximum Holter QTc values among all recordings were used for statistical analyses. To test the prognostic value of QTc for the appearance of cardiac events after the first hospital visit, receiver operating characteristic curves were used to calculate the area under the curve (AUC). Among 207 patients, 181 (87%) were diagnosed through screening programs. The prevalence of cardiac events after the first hospital visit was 4% (8/207). Among QTc at diagnosis, maximum resting QTc, and maximum Holter QTc, only maximum Holter QTc value was a predictor (P=0.02) of cardiac events after the hospital visit in multivariate regression analysis. The AUC of the maximum Holter QTc was significantly superior to that of maximum resting QTc.Conclusions: The maximum Holter QTc value can be used to predict the appearance of symptoms in pediatric patients with LQTS.

著者

Kazutaka Aonuma Tsuyoshi Shiga Hirotsugu Atarashi Kosuke Doki Hirotoshi Echizen Nobuhisa Hagiwara Junichi Hasegawa Hideharu Hayashi Kenzo Hirao Fukiko Ichida Takanori Ikeda Yorinobu Maeda Naoki Matsumoto Toshiyuki Sakaeda Wataru Shimizu Mitsuru Sugawara Kyoichi Totsuka Yoshimasa Tsuchishita Kazuyuki Ueno Eiichi Watanabe Masayuki Hashiguchi Sumio Hirata Hidefumi Kasai Yoshiaki Matsumoto Akihiko Nogami Yukio Sekiguchi Tokuko Shinohara Atsushi Sugiyama Naokata Sumitomo Atsushi Suzuki Naohiko Takahashi Eiji Yukawa Masato Homma Minoru Horie Hiroshi Inoue Hiroshi Ito Takanori Miura Tohru Ohe Kimikazu Shinozaki Kazuhiko Tanaka on behalf of the Japanese Circulation Society and the Japanese Society of Therapeutic Drug Monitoring Joint Working Group

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.81, no.4, pp.581-612, 2017-03-24 (Released:2017-03-24)

参考文献数

185

被引用文献数

33

著者

Kenji Nakatsuma Hiroki Shiomi Takeshi Morimoto Yutaka Furukawa Yoshihisa Nakagawa Kenji Ando Kazushige Kadota Takashi Yamamoto Satoru Suwa Minoru Horie Takeshi Kimura on behalf of the CREDO-Kyoto AMI investigators

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-16-0204, (Released:2016-06-28)

参考文献数

24

被引用文献数

2 22

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Background:Inter-facility transfer for primary percutaneous coronary intervention (PCI) from referring facilities to PCI centers causes a significant delay in treatment of ST-segment elevation acute myocardial infarction (STEMI) patients undergoing primary PCI. However, little is known about the clinical outcomes of STEMI patients undergoing inter-facility transfer in Japan.Methods and Results:In the CREDO-Kyoto acute myocardial infarction (AMI) registry that enrolled 5,429 consecutive AMI patients in 26 centers in Japan, the current study population consisted of 3,820 STEMI patients who underwent primary PCI within 24 h of symptom onset. We compared long-term clinical outcomes between inter-facility transfer patients and those directly admitted to PCI centers. The primary outcome measure was a composite of all-cause death or heart failure (HF) hospitalization. There were 1,725 (45.2%) inter-facility transfer patients, and 2,095 patients (54.8%) with direct admission to PCI centers. The cumulative 5-year incidence of death/HF hospitalization was significantly higher in the inter-facility transfer patients than in those with direct admission (26.9% vs. 22.2%; log-rank P<0.001). After adjusting for potential confounders, the risk for death/HF hospitalization was significantly higher (adjusted hazard ratio: 1.22, 95% confidence interval: 1.07–1.40, P<0.001) in the inter-facility transfer patients than in those directly admitted.Conclusions:Inter-facility transfer was associated with significantly worse long-term clinical outcomes for patients with STEMI undergoing primary PCI.

著者

Kenji Nakatsuma Hiroki Shiomi Takeshi Morimoto Kenji Ando Kazushige Kadota Hiroki Watanabe Tomohiko Taniguchi Takashi Yamamoto Yutaka Furukawa Yoshihisa Nakagawa Minoru Horie Takeshi Kimura on behalf of the CREDO-Kyoto AMI investigators

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-15-0870, (Released:2015-12-15)

参考文献数

19

被引用文献数

2 32

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Background:In the setting of elective percutaneous coronary intervention (PCI), intravascular ultrasound (IVUS)-guided PCI is associated with a reduction in the incidence of target vessel revascularization (TVR), but the impact of IVUS on long-term clinical outcome in the setting of emergency PCI for ST-segment elevation acute myocardial infarction (STEMI) is still unclear.Methods and Results:The subjects consisted of 3,028 STEMI patients who underwent primary PCI within 24 h of symptom onset in the CREDO-Kyoto acute myocardial infarction registry. Of these, 932 patients (31%) underwent IVUS-guided PCI. Compared with the angiography-guided PCI without IVUS, IVUS-guided PCI was associated with significantly lower incidences of TVR (primary outcome measure; 22% vs. 27%, log-rank P<0.001) and definite stent thrombosis (ST; 1.2% vs. 3.1%, log-rank P=0.003). The cumulative incidence of all-cause death was not significantly different between the 2 groups. After adjusting for confounders, however, there were no significant differences between the 2 groups in risk for TVR (adjusted HR, 1.14; 95% CI: 0.86–1.51, P=0.38) and definite ST (adjusted HR, 0.58; 95% CI: 0.19–1.72, P=0.33).Conclusions:IVUS-guided PCI was not associated with a lower risk for TVR or ST in STEMI patients undergoing primary PCI.

著者

Yuichi Sawayama Takashi Yamamoto Yukinori Tomita Kohei Asada Noriaki Yagi Megumi Fukuyama Akashi Miyamoto Hiroshi Sakai Tomoya Ozawa Tetsuichiro Isono Daiki Hira Tomohiro Terada Minoru Horie Yoshihisa Nakagawa

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.84, no.9, pp.1575-1581, 2020-08-25 (Released:2020-08-25)

参考文献数

18

被引用文献数

5 11

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Background:The association between cytochrome P450 (CYP) 2C19 genotypes and adverse events in patients treated with clopidogrel or prasugrel after percutaneous coronary intervention (PCI) in the Japanese population is unclear.Methods and Results:This study consisted of 1,580 patients whoseCYP2C19genotypes were assessed at Shiga University of Medical Science Hospital, and 193 clopidogrel-treated and 217 prasugrel-treated patients who were followed more than 1 year after receiving PCI were analyzed. Among 1,580 patients, the prevalence of normal, intermediate, and poor metabolizers was 32%, 49%, and 17%, respectively. Overall incidence of the primary outcome, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, ischemic stroke, or major bleeding was not significantly different between the clopidogrel and prasugrel groups (adjusted hazard ratio [HR] 1.98, 95% confidence interval [CI] 0.85–4.61, P=0.12). Among patients with theCYP2C19loss-of-function (LOF) allele, however, the incidence of the primary outcome was significantly higher in the clopidogrel group (adjusted HR 3.19, 95% CI 1.10–9.24, P=0.03), whereas no difference was observed among patients without theCYP2C19LOF allele (adjusted HR 0.67, 95% CI 0.14–3.26, P=0.62).Conclusions:Among patients with theCYP2C19LOF allele, the use of clopidogrel was significantly associated with increased adverse events. Thus, further investigation is needed to establish the practical use ofCYP2C19genotyping.

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

Toshiaki Toyota Takeshi Morimoto Hiroki Shiomi Kenji Ando Koh Ono Satoshi Shizuta Takao Kato Naritatsu Saito Yutaka Furukawa Yoshihisa Nakagawa Minoru Horie Takeshi Kimura on behalf of the CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-16-0987, (Released:2017-02-07)

参考文献数

31

被引用文献数

10

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Background:Few studies have evaluated the prevalence and clinical outcomes of ad hoc percutaneous coronary intervention (PCI), performing diagnostic coronary angiography and PCI in the same session, in stable coronary artery disease (CAD) patients.Methods and Results:From the CREDO-Kyoto PCI/CABG registry cohort-2, 6,943 patients were analyzed as having stable CAD and undergoing first PCI. Ad hoc PCI and non-ad hoc PCI were performed in 1,722 (24.8%) and 5,221 (75.1%) patients, respectively. The cumulative 5-year incidence and adjusted risk for all-cause death were not significantly different between the 2 groups (15% vs. 15%, P=0.53; hazard ratio: 1.15, 95% confidence interval: 0.98–1.35, P=0.08). Ad hoc PCI relative to non-ad hoc PCI was associated with neutral risk for myocardial infarction, any coronary revascularization, and bleeding, but was associated with a trend towards lower risk for stroke (hazard ratio: 0.78, 95% confidence interval: 0.60–1.02, P=0.06).Conclusions:Ad hoc PCI in stable CAD patients was associated with at least comparable 5-year clinical outcomes as with non-ad hoc PCI. Considering patients’ preference and the cost-saving, the ad hoc PCI strategy might be a safe and attractive option for patients with stable CAD, although the prevalence of ad hoc PCI was low in the current study population.

著者

Tomoko Sakaguchi Hideki Itoh Wei-Guang Ding Keiko Tsuji Iori Nagaoka Yuko Oka Takashi Ashihara Makoto Ito Yoshihiro Yumoto Naoko Zenda Yukei Higashi Youichi Takeyama Hiroshi Matsuura Minoru Horie

出版者

(公社)日本薬理学会

雑誌

Journal of Pharmacological Sciences (ISSN:13478613)

巻号頁・発行日

vol.108, no.4, pp.462-471, 2008 (Released:2008-12-20)

参考文献数

26

被引用文献数

14 30

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QT prolongation, a risk factor for arrhythmias, can result from genetic variants in one (or more) of the genes governing cardiac repolarization as well as intake of drugs known to affect a cardiac K+ channel encoded by human ether-a-go-go–related gene (HERG). In this paper, we will report a case of drug-induced long QT syndrome associated with an H1-receptor antagonist, hydroxyzine, in which a mutation was identified in the HERG gene. After taking 75 mg of hydroxyzine for several days, a 34-year-old female began to experience repetitive syncope. The deleterious effect of hydroxyzine was suspected because QTc interval shortened from 630 to 464 ms after cessation of the drug. Later on, the patient was found to harbor an A614V-HERG mutation. By using the patch-clamp technique in the heterologous expression system, we examined the functional outcome of the A614V mutation and confirmed a dominant-negative effect on HERG expression. Hydroxyzine concentration-dependently inhibited both wild-type (WT) and WT/A614V-HERG K+ currents. Half-maximum block concentrations of WT and WT/A614V-HERG K+ currents were 0.62 and 0.52 μM, respectively. Thus, accidental combination of genetic mutation and intake of hydroxyzine appeared to have led to a severe phenotype, probably, syncope due to torsade de pointes.

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.