Updated on 2022/10/01

写真a

 
MORITA Hiroshi
 
Organization
Faculty of Medicine, Dentistry and Pharmaceutical Sciences Professor
Position
Professor
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Research Interests

  • Cardiovascular Medicine

  • Arrhythmia

  • 突然死

  • 不整脈学

  • 循環器内科学

  • Sudden cardiac death

Research Areas

  • Life Science / Cardiology

Education

  • Okayama University   医学研究科   循環器内科

    1992.4 - 1996.3

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  • Okayama University   医学部   医学科

    1986.4 - 1992.3

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    Country: Japan

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Research History

  • - Professor,Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University

    2013.4

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  • Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,Okayama University   Cardiovascular Therapeutics   Professor

    2013.4

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    Country:Japan

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  • 岡山大学大学院医歯薬学総合研究科   准教授

    2010.4 - 2013.3

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  • 岡山大学大学院医歯薬学総合研究科   助教

    2008.4

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  • 岡山大学医学部・歯学部附属病院   医員

    2007.7 - 2008.3

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  • Krannert Institute of Cardiology, Indiana University School of Medicine 研究員

    2004 - 2007

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  • Medical Staff,Osaka City General Hospital

    1996 - 1997

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  • 大阪市立総合医療センター 職員(医療系)

    1996 - 1997

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Professional Memberships

Committee Memberships

  • 日本不整脈心電学会   利益相反部会 部会長  

    2020.12   

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  • 日本不整脈心電学会   中国・四国支部 運営委員  

    2019.9   

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    Committee type:Academic society

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  • Journal of Cardiology   Associate Editor  

    2018.9   

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  • 日本不整脈心電学会   利益相反委員会委員  

    2016.9   

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  • 日本不整脈心電学会   評議員  

    2015.5   

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  • Trend in Cardiovascular Medicine   Trend in Cardiovascular Medicine  

    2014.4   

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  • 日本内科学会   中国地方会評議員  

    2013   

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    Committee type:Academic society

    日本内科学会

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  • 日本循環器学会   中国地方会評議員  

    2013   

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    Committee type:Academic society

    日本循環器学会

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  • 日本心電学会   評議員  

    2009.1 - 2015.4   

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    Committee type:Academic society

    日本不整脈心電学会

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  • Heart Rhythm Society   Editorial board  

    2008   

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    Committee type:Academic society

    Heart Rhythm Society

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Papers

  • Fragmented QRS as a predictor of cardiac events in patients with cardiac sarcoidosis. International journal

    Soichiro Ogura, Kazufumi Nakamura, Hiroshi Morita, Koji Nakagawa, Nobuhiro Nishii, Satoshi Akagi, Norihisa Toh, Yoichi Takaya, Masashi Yoshida, Toru Miyoshi, Atsuyuki Watanabe, Hiroshi Ito

    Journal of cardiology   2021.11

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    BACKGROUND: Multiple spikes within the QRS complex, known as fragmented QRS (fQRS), are associated with the occurrences of ventricular arrhythmic events (VAEs) in patients with Brugada syndrome and hypertrophic cardiomyopathy. However, the association between fQRS and occurrence of VAEs in patients with cardiac sarcoidosis (CS) has not been elucidated. METHODS: We evaluated the associations between fQRS and cardiac events including VAEs [non-sustained ventricular tachycardia (NSVT), sustained ventricular tachycardia (VT), and ventricular fibrillation (VF)], hospitalization for heart failure, and all-cause death in 68 patients with CS (30 patients with fQRS vs. 38 patients without fQRS) over a 5-year period. RESULTS: Cardiac events occurred in 22 patients with fQRS and 18 patients without fQRS (73% vs. 47%, p=0.009). Of the cardiac events that occurred in CS patients, VAEs occurred more frequently in patients with fQRS than in patients without fQRS (VAEs: 70% vs. 45%, p=0.017; NSVT: 70% vs. 45%, p=0.010; VT: 43% vs. 18%, p=0.011, and VF: 6.7% vs. 2.6%, p=0.34), whereas there was no significant difference in hospitalization for heart failure or all-cause death between patients with and those without fQRS (hospitalization for heart failure: 6.7% vs. 5.3%, p=0.75; all-cause death: 6.7% vs. 5.3%, p=0.64). Multivariate analysis showed that fQRS in the baseline electrocardiogram was independently associated with VAEs (hazard ratio: 2.21, 95% confidence interval: 1.15-4.25, p=0.017). CONCLUSION: fQRS is a predictor of VAEs in patients with CS.

    DOI: 10.1016/j.jjcc.2021.10.022

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  • Successful ablation of a superior fast-slow atrioventricular reentrant tachycardia in a patient with congenitally corrected transposition of great arteries. International journal

    Satoshi Kawada, Nobuhiro Nishii, Saori Asada, Koji Nakagawa, Hiroshi Morita, Hiroshi Ito

    HeartRhythm case reports   7 ( 10 )   698 - 701   2021.10

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  • Effect of preprocedural pharmacologic cardioversion on pulmonary vein isolation in patients with persistent atrial fibrillation. International journal

    Keisuke Okawa, Shohei Hara, Takeshi Morimoto, Ryu Tsushima, Yuya Sudo, Masahiro Sogo, Masatomo Ozaki, Masahiko Takahashi, Masayuki Doi, Hiroshi Morita, Hiroshi Ito

    Heart rhythm   18 ( 9 )   1473 - 1479   2021.9

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    BACKGROUND: The optimal strategy for catheter ablation of persistent atrial fibrillation (PeAF) remains unknown. A preprocedural additive treatment for patients undergoing pulmonary vein isolation (PVI) alone to optimize catheter ablation should be investigated. OBJECTIVE: The purpose of this study was to determine whether pharmacologic cardioversion with a fixed low-dose antiarrhythmic drug (AAD) before ablation could stratify the long-term outcome of a PVI-alone strategy. METHODS: We conducted a prospective cohort study of PeAF patients who underwent PVI using contact force-sensing catheters. No substrate modification was performed. Fixed low-dose bepridil was administered before ablation for cardioversion and patients were classified into 2 groups based on obtaining sinus rhythm (SR). The rate of recurrence of atrial fibrillation (AF) and/or atrial tachycardia (AT) within 36 months was compared between the 2 groups. RESULTS: Among the 303 PeAF patients who received the AAD, 102 returned to SR (SR group), and the other 201 had persistence of AF (non-SR group). AF persistence duration at baseline and during bepridil administration was similar between the 2 groups. The SR group had a significantly lower 36-month AF/AT recurrence rate than the non-SR group (17 [22.2%] vs 55 [34.0%], log-rank P = .022). AT-type recurrence was observed in 16 patients (2 [3.3%] in the SR group vs 14 [8.9%] in the non-SR group; log-rank P = .051). Nonresponse to AAD was an independent predictor of AF/AT recurrence after adjusting for other risk factors (hazard ratio 1.34; 95% confidence interval 1.01-1.77; P = .040). CONCLUSION: Preprocedural pharmacologic cardioversion could be a useful determinant for patients with treatable PeAF by PVI alone.

    DOI: 10.1016/j.hrthm.2021.04.027

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  • Who is at high-risk in J wave syndromes? International journal

    Hiroshi Morita, Masakazu Miyamoto

    Trends in cardiovascular medicine   2021.8

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  • Pathological and clinical effects of interleukin-6 on human myocarditis. International journal

    Naofumi Amioka, Kazufumi Nakamura, Tomonari Kimura, Keiko Ohta-Ogo, Takehiro Tanaka, Tomohiro Toji, Satoshi Akagi, Koji Nakagawa, Norihisa Toh, Masashi Yoshida, Toru Miyoshi, Nobuhiro Nishii, Atsuyuki Watanabe, Ryotaro Asano, Takeshi Ogo, Yoshikazu Nakaoka, Hiroshi Morita, Hiroyuki Yanai, Hiroshi Ito

    Journal of cardiology   78 ( 2 )   157 - 165   2021.8

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    BACKGROUND: Numerous basic studies have shown a relationship between interleukin-6 (IL-6) and the development or severity of myocarditis. However, there has been no study in which the effect of IL-6 levels in patients with myocarditis was evaluated. METHODS: We enrolled control patients (n = 12) and consecutive patients with acute myocarditis (n = 13), including lymphocytic, eosinophilic, and giant cell myocarditis, and investigated the pathological and clinical effects of IL-6 on human myocarditis. RESULTS: The serum IL-6 level in patients with myocarditis (16.7 [9.9, 103.8] pg/mL) was significantly higher than that in the control patients (1.4 [1.0, 1.9] pg/mL) (P<0.001). Immunohistochemical analysis showed that IL-6 was expressed in infiltrating inflammatory cells of endomyocardial biopsy samples from all patients with myocarditis. Moreover, the log-transformed value of serum IL-6 level showed significant positive correlations with serum creatine kinase (CK) level, CK-MB level, peak CK level, peak CK-MB level and C-reactive protein level (all P ≤ 0.005) and a negative correlation with the left ventricular (LV) ejection fraction (p = 0.014). We divided the patients with myocarditis into a low IL-6 group (9.9 [4.5, 14.2] pg/dL, n = 7) and a high IL-6 group (108.9 [51.1, 130.9] pg/dL, n = 6). The degree of infiltration of IL-6-expressing inflammatory cells in myocardial samples obtained from patients in the high IL-6 group was significantly more severe than that in samples obtained from patients in the low IL-6 group. Furthermore, patients in the high IL-6 group significantly more frequently received catecholamine therapy (P = 0.005), venoarterial extracorporeal membrane oxygenation (P = 0.029), and artificial respirator support (P = 0.021) in the acute phase of myocarditis. CONCLUSION: The results suggest that there is a strong impact of IL-6 on cardiac injury and dysfunction in patients with myocarditis.

    DOI: 10.1016/j.jjcc.2021.03.003

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  • Functionally validated SCN5A variants allow interpretation of pathogenicity and prediction of lethal events in Brugada syndrome. International journal

    Taisuke Ishikawa, Hiroki Kimoto, Hiroyuki Mishima, Kenichiro Yamagata, Soshiro Ogata, Yoshiyasu Aizawa, Kenshi Hayashi, Hiroshi Morita, Tadashi Nakajima, Yukiko Nakano, Satoshi Nagase, Nobuyuki Murakoshi, Shinya Kowase, Kimie Ohkubo, Takeshi Aiba, Shimpei Morimoto, Seiko Ohno, Shiro Kamakura, Akihiko Nogami, Masahiko Takagi, Matilde Karakachoff, Christian Dina, Jean-Jacques Schott, Koh-Ichiro Yoshiura, Minoru Horie, Wataru Shimizu, Kunihiro Nishimura, Kengo Kusano, Naomasa Makita

    European heart journal   42 ( 29 )   2854 - 2863   2021.7

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    AIMS: The prognostic value of genetic variants for predicting lethal arrhythmic events (LAEs) in Brugada syndrome (BrS) remains controversial. We investigated whether the functional curation of SCN5A variations improves prognostic predictability. METHODS AND RESULTS: Using a heterologous expression system and whole-cell patch clamping, we functionally characterized 22 variants of unknown significance (VUSs) among 55 SCN5A mutations previously curated using in silico prediction algorithms in the Japanese BrS registry (n = 415). According to the loss-of-function (LOF) properties, SCN5A mutation carriers (n = 60) were divided into two groups: LOF-SCN5A mutations and non-LOF SCN5A variations. Functionally proven LOF-SCN5A mutation carriers (n = 45) showed significantly severer electrocardiographic conduction abnormalities and worse prognosis associated with earlier manifestations of LAEs (7.9%/year) than in silico algorithm-predicted SCN5A carriers (5.1%/year) or all BrS probands (2.5%/year). Notably, non-LOF SCN5A variation carriers (n = 15) exhibited no LAEs during the follow-up period. Multivariate analysis demonstrated that only LOF-SCN5A mutations and a history of aborted cardiac arrest were significant predictors of LAEs. Gene-based association studies using whole-exome sequencing data on another independent SCN5A mutation-negative BrS cohort (n = 288) showed no significant enrichment of rare variants in 16 985 genes including 22 non-SCN5A BrS-associated genes as compared with controls (n = 372). Furthermore, rare variations of non-SCN5A BrS-associated genes did not affect LAE-free survival curves. CONCLUSION: In vitro functional validation is key to classifying the pathogenicity of SCN5A VUSs and for risk stratification of genetic predictors of LAEs. Functionally proven LOF-SCN5A mutations are genetic burdens of sudden death in BrS, but evidence for other BrS-associated genes is elusive.

    DOI: 10.1093/eurheartj/ehab254

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  • Incremental prognostic value of non-alcoholic fatty liver disease over coronary computed tomography angiography findings in patients with suspected coronary artery disease. International journal

    Keishi Ichikawa, Toru Miyoshi, Kazuhiro Osawa, Takashi Miki, Hironobu Toda, Kentaro Ejiri, Masashi Yoshida, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    European journal of preventive cardiology   2021.7

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    AIMS: This study aimed to investigate additional risk stratification benefits of hepatic steatosis (HS) concurrently assessed during coronary computed tomography angiography (CTA) in a large patient cohort with suspected stable coronary artery disease (CAD). METHODS AND RESULTS: In this prospective study, 1148 Japanese outpatients without a history of CAD who underwent coronary CTA for suspected stable CAD (mean age 64 ± 14 years) were included. HS, defined on CT as a hepatic-to-spleen attenuation ratio of <1.0, was examined just before the evaluation of adverse CTA findings, defined as obstructive and/or high-risk plaque. The major adverse cardiac events (MACE) were the composite of cardiac death, acute coronary syndrome, and late revascularization. The incremental predictive value of HS was evaluated using the global χ2 test and C-statistic. HS was identified in 247 (22%) patients. During a median follow-up of 3.9 years, MACE was observed in 40 (3.5%) patients. HS was significantly associated with MACE in a model that included adverse CTA findings (hazard ratio 4.01, 95% confidence interval 2.12-7.59, P < 0.001). By adding HS to the Framingham risk score and adverse CTA findings, the global χ2 score and C-statistic significantly increased from 29.0 to 49.5 (P < 0.001) and 0.74 to 0.81 (P = 0.026), respectively. In subgroup analyses in patients with diabetes mellitus and metabolic syndrome, HS had significant additive predictive value for MACE over the Framingham risk score and adverse CTA findings. CONCLUSION: In patients with suspected stable CAD, concurrent evaluation of HS during coronary CTA enables more accurate detection of patients at higher risk of MACE.

    DOI: 10.1093/eurjpc/zwab120

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  • Higher oxidized high-density lipoprotein to apolipoprotein A-I ratio is associated with high-risk coronary plaque characteristics determined by CT angiography. International journal

    Kazuki Suruga, Toru Miyoshi, Kazuhiko Kotani, Keishi Ichikawa, Takashi Miki, Kazuhiro Osawa, Kentaro Ejiri, Hironobu Toda, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    International journal of cardiology   324   193 - 198   2021.2

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    BACKGROUND: Oxidized high-density lipoprotein (oxHDL), unlike native HDL, is characterized by reduced cholesterol efflux capability and anti-inflammatory properties. The ratio of oxHDL to apolipoprotein A-I (oxHDL/apoAI) is a possible marker of dysfunctional HDL. The aim of this study was to evaluate the association between oxHDL/apoAI and coronary plaque characteristics that increase the likelihood of cardiovascular events as determined by coronary computed tomography (CT) angiography. METHODS: A total of 297 patients (mean age; 67 years, men; 63%) who underwent coronary CT angiography for suspected stable coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined by three characteristics: positive remodeling; low-density plaques; and spotty calcification. Significant stenosis was defined as a luminal narrowing of >70%. Serum concentrations of oxHDL were measured using an enzyme-linked immunosorbent assay. RESULTS: Patients with higher oxHDL/ApoAI showed significantly greater prevalence of HRP (p = 0.03) and significant stenosis (p < 0.01) compared with patients with low oxHDL/ ApoAI. The multivariate logistic analysis demonstrated that oxHDL/ApoAI significantly associated with the presence of HRP and significant coronary stenosis (p = 0.01 and < 0.01). In the follow-up study including 243 patients for a median period of 1.8 years, univariate cox regression analysis showed that oxHDL/ApoAI, HRP and significant stenosis were significant predictors of cardiovascular events. CONCLUSIONS: A high oxHDL/apoAI was associated with the presence of HRP and significant stenosis determined by coronary CT angiography, which can lead to cardiovascular events in patients with suspected stable CAD.

    DOI: 10.1016/j.ijcard.2020.09.060

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  • Prognosis of patients with severe left ventricular dysfunction after transvenous lead extraction and the need for additional hemodynamic support in the perioperative period. International journal

    Nobuhiro Nishii, Takashi Nishimoto, Tomofumi Mizuno, Takuro Masuda, Saori Asada, Masakazu Miyamoto, Satoshi Kawada, Koji Nakagawa, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Morimatsu, Shingo Kasahara, Hiroshi Ito

    Heart rhythm   18 ( 6 )   962 - 969   2021.1

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    BACKGROUND: Transvenous lead extraction (TLE) is necessary because of system infection, lead malfunction, or system upgrade. Patients with severe left ventricular dysfunction (SLVD) undergoing TLE may be at a higher risk because hemodynamic parameters may change unfavorably during or after TLE; however, this has not yet been clarified. OBJECTIVE: The purpose of this study was to examine whether patients with SLVD undergoing TLE have higher mortality. METHODS: All patients who underwent TLE were stratified as follows: patients with ejection fraction ≤ 35% (SLVD group) and those with ejection fraction > 35% (non-SLVD group). RESULTS: We assessed the data of 200 patients (SLVD group, 36; non-SLVD group, 164). Brain natriuretic peptide level and cardiac resynchronization therapy rate were higher in the SLVD group than in the non-SLVD group. There were no significant between-group differences in major complications and clinical success rates. Patients with SLVD were more likely to require additional hemodynamic support, such as catecholamine infusion, temporary atrial-ventricle sequential pacing, and temporary cardiac resynchronization therapy pacing (27.8% vs 1.2%; P < .001). The survival rate was not significantly different between the groups at 30 days and 1 year after TLE (SLVD vs non-SLVD: 30 days: 97.2% vs 99.4%; P = .215; 1 year: 80.6% vs 91.5%; P = .053). Multivariate Cox regression analysis revealed log brain natriuretic peptide and serum hemoglobin levels as predictors for 1-year mortality. CONCLUSION: The prognosis after TLE was comparable between patients with and without SLVD. However, additional hemodynamic support was often necessary for patients with SLVD.

    DOI: 10.1016/j.hrthm.2021.01.026

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  • Prognostic value of non-alcoholic fatty liver disease for predicting cardiovascular events in patients with diabetes mellitus with suspected coronary artery disease: a prospective cohort study. International journal

    Keishi Ichikawa, Toru Miyoshi, Kazuhiro Osawa, Takashi Miki, Hironobu Toda, Kentaro Ejiri, Masatoki Yoshida, Yusuke Nanba, Masashi Yoshida, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    Cardiovascular diabetology   20 ( 1 )   8 - 8   2021.1

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    BACKGROUND: Risk stratification of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) has not been established. Coronary artery calcium score (CACS) and non-alcoholic fatty liver disease (NAFLD) are independently associated with cardiovascular events in T2DM patients. This study examined the incremental prognostic value of NAFLD assessed by non-enhanced computed tomography (CT) in addition to CACS and Framingham risk score (FRS) for cardiovascular events in T2DM patients. METHODS: This prospective pilot study included 529 T2DM outpatients with no history of cardiovascular disease who underwent CACS measurement because of suspected coronary artery disease. NAFLD was defined on CT images as a liver:spleen attenuation ratio < 1.0. Cardiovascular events were defined as cardiovascular death, nonfatal myocardial infarction, late coronary revascularization, nonfatal stroke, or hospitalization for heart failure. RESULTS: Among 529 patients (61% men, mean age 65 years), NAFLD was identified in 143 (27%). Forty-four cardiovascular events were documented during a median follow-up of 4.4 years. In multivariate Cox regression analysis, NAFLD, CACS, and FRS were associated with cardiovascular events (hazard ratios and 95% confidence intervals 5.43, 2.82-10.44, p < 0.001; 1.56, 1.32-1.86, p < 0.001; 1.23, 1.08-1.39, p = 0.001, respectively). The global χ2 score for predicting cardiovascular events increased significantly from 27.0 to 49.7 by adding NAFLD to CACS and FRS (p < 0.001). The addition of NAFLD to a model including CACS and FRS significantly increased the C-statistic from 0.71 to 0.80 (p = 0.005). The net reclassification achieved by adding CACS and FRS was 0.551 (p < 0.001). CONCLUSIONS: NAFLD assessed by CT, in addition to CACS and FRS, could be useful for identifying T2DM patients at higher risk of cardiovascular events.

    DOI: 10.1186/s12933-020-01192-4

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  • Usefulness of right ventriculography compared with computed tomography for ruling out the possibility of lead perforation before lead extraction. International journal

    Saori Asada, Nobuhiro Nishii, Takayoshi Shinya, Akihito Miyoshi, Yoshimasa Morimoto, Masakazu Miyamoto, Koji Nakagawa, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    PloS one   16 ( 3 )   e0245502   2021

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    PURPOSE: High-risk patients can be identified by preprocedural computed tomography (CT) before lead extraction. However, CT evaluation may be difficult especially for lead tip identification due to artifacts in the leads. Selective right ventriculography (RVG) may enable preprocedural evaluation of lead perforation. We investigated the efficacy of RVG for identifying right ventricular (RV) lead perforation compared with CT in patients who underwent lead extraction. METHODS: Ninety-five consecutive patients who were examined by thin-section non-ECG-gated multidetector CT and RVG before lead extraction were investigated retrospectively. Newly recognized pericardial effusion after lead extraction was used as a reference standard for lead perforation. We analyzed the prevalence of RV lead perforation diagnosed by each method. The difference in the detection rates of lead perforation by RVG and CT was evaluated. RESULTS: Of the 115 RV leads in the 95 patients, lead perforation was diagnosed for 35 leads using CT, but the leads for 29 (83%) of those 35 leads diagnosed as lead perforation by CT were shown to be within the right ventricle by RVG. Three patients with 5 leads could not be evaluated by CT due to motion artifacts. The diagnostic accuracies of RVG and CT were significantly different (p < 0.001). There was no complication of pericardial effusion caused by RV lead extraction. CONCLUSION: RVG for identification of RV lead perforation leads to fewer false-positives compared to non-ECG-gated CT. However, even in cases in which lead perforation is diagnosed, most leads may be safely extracted by transvenous lead extraction.

    DOI: 10.1371/journal.pone.0245502

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  • Significance of Exercise-Related Ventricular Arrhythmias in Patients With Brugada Syndrome. International journal

    Hiroshi Morita, Saori T Asada, Masakazu Miyamoto, Yoshimasa Morimoto, Tomonari Kimura, Tomofumi Mizuno, Koji Nakagawa, Atsuyuki Watanabe, Nobuhiro Nishii, Hiroshi Ito

    Journal of the American Heart Association   9 ( 23 )   e016907   2020.12

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    Background Sinus tachycardia during exercise attenuates ST-segment elevation in patients with Brugada syndrome, whereas ST-segment augmentation after an exercise test is a high-risk sign. Some patients have premature ventricular contractions (PVCs) related to exercise, but the significance of exercise-related PVCs in patients with Brugada syndrome is still unknown. The objective of this study was to determine the significance of exercise-related PVCs for predicting occurrence of ventricular fibrillation (VF) in patients with Brugada syndrome. Methods and Results The subjects were 307 patients with Brugada syndrome who performed a treadmill exercise test. We evaluated the occurrence of PVCs at rest, during exercise and at the peak of exercise, and during recovery after exercise (0-5 minutes). We followed the patients for 92±68 months and evaluated the occurrence of VF. PVCs occurred in 82 patients (27%) at the time of treadmill exercise test: PVCs appeared at rest in 14 patients (4%), during exercise in 60 patients (20%), immediately after exercise (0-1.5 minutes) in 28 patients (9%), early after exercise (1.5-3 minutes) in 18 patients (6%), and late after exercise (3-5 minutes) in 12 patients (4%). Thirty patients experienced VF during follow-up. Multivariable analysis including symptoms, spontaneous type 1 ECG, and PVCs in the early recovery phase showed that these factors were independently associated with VF events during follow-up. Conclusions PVCs early after an exercise test are associated with future occurrence of VF events. Rebound of vagal nerve activity at the early recovery phase would promote ST-segment augmentation and PVCs in high-risk patients with Brugada syndrome.

    DOI: 10.1161/JAHA.120.016907

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  • Improvement in renal and endothelial function after catheter ablation in patients with persistent atrial fibrillation. International journal

    Keisuke Okawa, Toru Miyoshi, Masahiro Sogo, Shohei Hara, Yuya Sudo, Satoko Ugawa, Masahiko Takahashi, Masayuki Doi, Hiroshi Morita, Hiroshi Ito

    Journal of cardiology   76 ( 6 )   610 - 617   2020.12

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    BACKGROUND: Cardiovascular events in patients with atrial fibrillation (AF) can be lowered by catheter ablation. We hypothesized the underlying mechanism was improvement in renal and endothelial function corresponding to AF burden, and investigated whether restoration of sinus rhythm (SR) after ablation affected these functions according to AF type. METHODS AND RESULTS: We prospectively measured estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), and reactive hyperemia index (RHI) in 358 consecutive patients with AF before and 6 and 12 months after the ablation. For each AF type [paroxysmal AF (PAF), n = 229, and persistent AF (PeAF), n = 129], we evaluated changes in these markers and influence of chronic kidney disease (CKD). The eGFR and natural logarithm-transformed (ln) UACR improved at 6 months in the PeAF group (68.7 ± 18.7-71.8 ± 18.9 mL/min/1.73 m2, p = 0.003 and 3.1±1.6 to 2.8±1.5, p < 0.001, respectively) and remained unchanged in the PAF group. Among the PeAF patients, recurrent AF was identified in 41, but only transiently in 38 patients. PeAF at baseline independently predicted increased eGFR [odds ratio (OR)=2.13, 95 % confidence interval (CI) 1.35-3.40, p = 0.001] and decreased UACR (OR=1.94, 95 % CI 1.05-3.58, p = 0.033). In the PeAF patients with CKD, ln-RHI significantly increased at 6 months after the ablation, and the change (Δ) in ln-RHI was significantly correlated with the ΔeGFR (r=0.35, p = 0.03). CONCLUSIONS: SR restoration after ablation was associated with an improved eGFR and UACR in PeAF patients, but not PAF patients. In PeAF patients with CKD, an improved endothelial function after ablation was associated with an improved renal function.

    DOI: 10.1016/j.jjcc.2020.07.002

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  • Improved Risk Stratification of Patients With Brugada Syndrome by the New Japanese Circulation Society Guideline - A Multicenter Validation Study.

    Akinori Wakamiya, Tsukasa Kamakura, Tetsuji Shinohara, Kenji Yodogawa, Nobuyuki Murakoshi, Hiroshi Morita, Naohiko Takahashi, Yasuya Inden, Wataru Shimizu, Akihiko Nogami, Minoru Horie, Kenzaburo Nakajima, Naoya Kataoka, Mitsuru Wada, Kenichiro Yamagata, Kohei Ishibashi, Yuko Inoue, Koji Miyamoto, Satoshi Nagase, Takashi Noda, Takeshi Aiba, Satoshi Yasuda, Masaki Ieda, Kengo Kusano

    Circulation journal : official journal of the Japanese Circulation Society   84 ( 12 )   2158 - 2165   2020.11

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    BACKGROUND: The new guideline (NG) published by the Japanese Circulation Society (JCS) places emphasis on previous arrhythmic syncope and inducibility of ventricular fibrillation (VF) by ≤2 extrastimuli during programmed electrical stimulation (PES) for deciding the indication of an implantable cardioverter-defibrillator in patients with Brugada syndrome (BrS). This study evaluated the usefulness of the NG and compared it with the former guideline (FG) for risk stratification of patients with BrS.Methods and Results:This was a multicenter (7 Japanese hospitals) retrospective study involving 234 patients with BrS who underwent PES at baseline (226 males; mean age at diagnosis: 44.9±13.4 years). At diagnosis, 46 patients (20%) had previous VF, 100 patients (43%) had previous syncope, and 88 patients (37%) were asymptomatic. We evaluated the difference in the incidence of VF in each indication according to the new and FGs. During the follow-up period (mean: 6.9±5.2 years), the incidence of VF was higher in patients with Class IIa indication according to the NG (NG: 16/45 patients [35.6%] vs. FG: 16/104 patients [15.4%]), while the incidence of VF in patients with other than class I or IIa indication was similarly low in both guidelines (NG: 2/143 patients [1.4%] vs. FG: 2/84 patients [2.4%]). CONCLUSIONS: This study validated the usefulness of the NG for risk stratification of BrS patients.

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  • 救急外来での見逃し(Missed)を避けるべき心原性失神10 real cases approach

    藤本 竜平, 森田 宏, 間瀬 浩, 三木 崇史, 戸田 洋伸, 杜 徳尚, 西井 伸洋, 中村 一文, 鈴木 洋, 伊藤 浩

    日本救急医学会雑誌   31 ( 11 )   2280 - 2280   2020.11

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  • Ablation for idiopathic left ventricular tachycardia in a patient with double outlet right ventricle who underwent Fontan operation: a case report. International journal

    Masakazu Miyamoto, Nobuhiro Nishii, Hiroshi Morita, Hiroshi Ito

    European heart journal. Case reports   4 ( 5 )   1 - 6   2020.10

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    Background: The incidence of ventricular tachycardia (VT) in patients following Fontan operation is reported as 3.5%. Furthermore, in patients with repaired double outlet right ventricle (DORV), scar-related VT and outflow tract VT have been reported; however, Purkinje-related VT has not previously been reported. In this report, we present the case of idiopathic left VT (ILVT) in a patient with DORV who underwent Fontan operation. Case summary: A 31-year-old man was diagnosed as having DORV with complete atrioventricular defect at birth. When he was 17 years old, he underwent surgical repair, including extracardiac Fontan operation and common atrioventricular valve replacement. Five years later, VT was detected. Since some medications were ineffective in suppressing VT, he was referred to our hospital for definitive treatment. Ventricular tachycardia was induced by atrial and ventricular programmed electrical stimulations. The mechanism of the VT was determined to be re-entry. The earliest activation site was located at the mid-inferior septum of the hypoplastic left ventricle, in which Purkinje potentials were observed before the local ventricular electrogram. Radiofrequency catheter ablation (RFCA) was performed at this site to eliminate VT. Discussion: Most VTs originate from surgical scars in patients with congenital heart disease. Catheter ablation was feasible in scar-related VT. To the best of our knowledge, this is the first report of ILVT treated successfully with RFCA in a DORV patient who had undergone Fontan operation.

    DOI: 10.1093/ehjcr/ytaa264

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  • Systematic Evaluation of KCNQ1 Variant Using ACMG/AMP Guidelines and Risk Stratification in Long QT Syndrome Type 1. International journal

    Asami Kashiwa, Takeshi Aiba, Hisaki Makimoto, Keiko Shimamoto, Kenichiro Yamagata, Tsukasa Kamakura, Mitsuru Wada, Koji Miyamoto, Yuko Inoue-Yamada, Kohei Ishibashi, Takashi Noda, Satoshi Nagase, Aya Miyazaki, Heima Sakaguchi, Isao Shiraishi, Nobue Yagihara, Hiroshi Watanabe, Yoshifusa Aizawa, Takeru Makiyama, Hideki Itoh, Kenshi Hayashi, Masakazu Yamagishi, Naotaka Sumitomo, Masao Yoshinaga, Hiroshi Morita, Tohru Ohe, Yoshihiro Miyamoto, Naomasa Makita, Satoshi Yasuda, Kengo Kusano, Seiko Ohno, Minoru Horie, Wataru Shimizu

    Circulation. Genomic and precision medicine   2020.9

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    Background - Mutation/variant-site specific risk stratification in long-QT syndrome type 1 (LQT1) has been well investigated, but it is still challenging to adapt current enormous genomic information to clinical aspects caused by each mutation/variant. We assessed a novel variant-specific risk stratification in LQT1 patients. Methods - We classified a pathogenicity of 141 KCNQ1 variants among 927 LQT1 patients (536 probands) based on the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP) guidelines and evaluated whether the ACMG/AMP-based classification was associated with arrhythmic risk in LQT1 patients. Results - Among 141 KCNQ1 variants, 61 (43.3%), 55 (39.0%), and 25 (17.7%) variants were classified into pathogenic (P), likely pathogenic (LP), and variant of unknown significance (VUS), respectively. Multivariable analysis showed that proband (HR = 2.53; 95%CI = 1.94-3.32; p <0.0001), longer QTc (≥500ms) (HR = 1.44; 95%CI = 1.13-1.83; p = 0.004), variants at membrane spanning (MS) (vs. those at N/C terminus) (HR = 1.42; 95%CI = 1.08-1.88; p = 0.01), C-loop (vs. N/C terminus) (HR = 1.52; 95%CI = 1.06-2.16; p = 0.02), and P variants [(vs. LP) (HR = 1.72; 95%CI = 1.32-2.26; p <0.0001), (vs. VUS) (HR = 1.81; 95%CI = 1.15-2.99; p = 0.009)] were significantly associated with syncopal events. The ACMG/AMP-based KCNQ1 evaluation was useful for risk stratification not only in family members but also in probands. A clinical score (0~4) based on proband, QTc (≥500ms), variant location (MS or C-loop) and P variant by ACMG/AMP guidelines allowed identification of patients more likely to have arrhythmic events. Conclusions - Comprehensive evaluation of clinical findings and pathogenicity of KCNQ1 variants based on the ACMG/AMP-based evaluation may stratify arrhythmic risk of congenital long-QT syndrome type 1.

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  • Indication and prognostic significance of programmed ventricular stimulation in asymptomatic patients with Brugada syndrome. International journal

    Saori Asada, Hiroshi Morita, Atsuyuki Watanabe, Koji Nakagawa, Satoshi Nagase, Masakazu Miyamoto, Yoshimasa Morimoto, Satoshi Kawada, Nobuhiro Nishii, Hiroshi Ito

    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology   22 ( 6 )   972 - 979   2020.6

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    AIMS: To establish the indication for programmed ventricular stimulation (PVS) for asymptomatic patients with Brugada syndrome (BrS), we evaluated the prognostic significance of PVS based on abnormal electrocardiogram (ECG) markers. METHODS AND RESULTS: One hundred and twenty-five asymptomatic patients with BrS were included. We performed PVS at two sites of the right ventricle with up to three extrastimuli [two pacing cycle lengths and minimum coupling interval (MCI) of 180 ms]. We followed the patients for 133 months and evaluated ventricular fibrillation (VF) events. Fragmented QRS (fQRS) and Tpeak-Tend (Tpe) interval were evaluated as ECG markers for identifying high-risk patients. Fragmented QRS and long Tpe interval (≥100 ms) were observed in 66 and 37 patients, respectively. Ventricular fibrillation was induced by PVS in 60 patients. During follow-up, 10 patients experienced VF events. Fragmented QRS, long Tpe interval, and PVS-induced VF with an MCI of 180 ms or up to two extrastimuli were associated with future VF events (fQRS: P = 0.015, Tpe ≥ 100 ms: P = 0.038, VF induction: P < 0.001). However, PVS-induced VF with an MCI of 200 ms was less specific (P = 0.049). The frequencies of ventricular tachyarrhythmia events during follow-up were 0%/year with no ECG markers and 0.1%/year with no VF induction. The existence of two ECG factors with induced VF was strongly associated with future VF events (event rate: 4.4%/year, P < 0.001), and the existence of one ECG factor with induced VF was also associated (event rate: 1.3%/year, P = 0.011). CONCLUSION: We propose PVS with a strict protocol for asymptomatic patients with fQRS and/or long Tpe interval to identify high-risk patients.

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  • Identification of transmembrane protein 168 mutation in familial Brugada syndrome. International journal

    Akio Shimizu, Dimitar P Zankov, Akira Sato, Masahiro Komeno, Futoshi Toyoda, Satoru Yamazaki, Toshinori Makita, Taichi Noda, Masahito Ikawa, Yoshihiro Asano, Yohei Miyashita, Seiji Takashima, Hiroshi Morita, Taisuke Ishikawa, Naomasa Makita, Masahito Hitosugi, Hiroshi Matsuura, Seiko Ohno, Minoru Horie, Hisakazu Ogita

    FASEB journal : official publication of the Federation of American Societies for Experimental Biology   34 ( 5 )   6399 - 6417   2020.5

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    Brugada syndrome (BrS) is an inherited channelopathy responsible for almost 20% of sudden cardiac deaths in patients with nonstructural cardiac diseases. Approximately 70% of BrS patients, the causative gene mutation(s) remains unknown. In this study, we used whole exome sequencing to investigate candidate mutations in a family clinically diagnosed with BrS. A heterozygous 1616G>A substitution (R539Q mutation) was identified in the transmembrane protein 168 (TMEM168) gene of symptomatic individuals. Similar to endogenous TMEM168, both TMEM168 wild-type (WT) and mutant proteins that were ectopically induced in HL-1 cells showed nuclear membrane localization. A significant decrease in Na+ current and Nav 1.5 protein expression was observed in HL-1 cardiomyocytes expressing mutant TMEM168. Ventricular tachyarrhythmias and conduction disorders were induced in the heterozygous Tmem168 1616G>A knock-in mice by pharmacological stimulation, but not in WT mice. Na+ current was reduced in ventricular cardiomyocytes isolated from the Tmem168 knock-in heart, and Nav 1.5 expression was also impaired. This impairment was dependent on increased Nedd4-2 binding to Nav 1.5 and subsequent ubiquitination. Collectively, our results show an association between the TMEM168 1616G>A mutation and arrhythmogenesis in a family with BrS.

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  • Effects of Bisoprolol Transdermal Patches for Prevention of Perioperative Myocardial Injury in High-Risk Patients Undergoing Non-Cardiac Surgery - Multicenter Randomized Controlled Study.

    Hironobu Toda, Kazufumi Nakamura, Kazuyoshi Shimizu, Kentaro Ejiri, Takayuki Iwano, Toru Miyoshi, Koji Nakagawa, Masashi Yoshida, Atsuyuki Watanabe, Nobuhiro Nishii, Yukiko Hikasa, Masao Hayashi, Hiroshi Morita, Hiroshi Morimatsu, Hiroshi Ito

    Circulation journal : official journal of the Japanese Circulation Society   84 ( 4 )   642 - 649   2020.3

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    BACKGROUND: The aim of this study was to evaluate the efficacy and safety of transdermal β-blocker patches, which offer stable blood concentration and easy availability during operation, for prevention of perioperative myocardial injury (PMI) in high-risk patients.Methods and Results:In this randomized controlled trial, patients aged >60 years with hypertension and high revised cardiac risk index (≥2) undergoing non-cardiac surgery were randomly assigned to a bisoprolol patch or control group. Primary efficacy outcome was incidence of PMI, defined as postoperative high-sensitivity cardiac troponin T (hs-cTnT) >0.014ng/mL and relative hs-cTnT change ≥20%. Secondary efficacy outcomes were number of cardiovascular events and 30-day mortality. From November 2014 to February 2019, 240 patients from 5 hospitals were enrolled in this study. The incidence of PMI was 35.7% in the bisoprolol patch group and 44.5% in the control group (P=0.18). Incidence of major adverse cardiac events including non-critical myocardial infarction, strokes, decompensated heart failure and tachyarrhythmia was similar between the 2 groups. Tachyarrhythmia tended to be higher in the control group. There were no significant differences in safety outcomes including significant hypotension and bradycardia requiring any treatment between the 2 groups. CONCLUSIONS: Bisoprolol patches do not influence the incidence of PMI and cardiovascular events in high-risk patients undergoing non-cardiac surgery, but perioperative use of these patches is safe.

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  • Lifestyle Modification or Medication to Improve Condition of Patients With Asymptomatic Heart Failure - Monitoring and Management of OptiVol Alert to Reduce Heart Failure Hospitalization II (MOMOTARO II) Study.

    Akihito Miyoshi, Nobuhiro Nishii, Yoji Okamoto, Shinpei Fujita, Kenji Kawamoto, Keisuke Okawa, Shigeki Hiramatsu, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    Circulation journal : official journal of the Japanese Circulation Society   84 ( 3 )   456 - 462   2020.2

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    BACKGROUND: In heart failure (HF) patients implanted with high-energy devices, worsening of HF can be diagnosed from intrathoracic impedance (ITI) before symptoms appear. Early therapeutic intervention can prevent HF worsening, but the optimal intervention remains unknown. This study aimed to examine which lifestyle modifications or medications can improve HF indicators in asymptomatic HF patients diagnosed from ITI.Methods and Results:This multicenter, prospective, randomized study included patients with high-energy devices, left ventricular ejection fraction <40%, or with a history of HF hospitalization. After the OptiVol alert was evoked by decreased ITI, patients underwent examinations. If they were diagnosed with HF, they were randomly assigned to 3 groups: lifestyle modification, diuretic, or nitrate. After 1 week, they underwent the same examinations. The primary endpoint was change in ITI and serum B-type natriuretic peptide (BNP). Totally, 57 patients were randomized. In all 3 groups, ITI was significantly increased post-intervention compared with pre-intervention. In the diuretic and nitrate groups, logBNP post-intervention was significantly lower than pre-intervention, but not in the lifestyle modification group. CONCLUSIONS: Compared with lifestyle modifications, diuretic and nitrate therapy for 1 week may be more effective management of HF detected by decreased ITI. However, lifestyle modification may have the additional benefits of reducing the workload or cost.

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  • New Appearance of Fragmented QRS as a Predictor of Ventricular Arrhythmic Events in Patients With Hypertrophic Cardiomyopathy.

    Soichiro Ogura, Kazufumi Nakamura, Hiroshi Morita, Norihisa Toh, Koji Nakagawa, Masashi Yoshida, Atsuyuki Watanabe, Nobuhiro Nishii, Toru Miyoshi, Hiroshi Ito

    Circulation journal : official journal of the Japanese Circulation Society   84 ( 3 )   487 - 494   2020.2

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    BACKGROUND: Multiple spikes in the QRS complex (fragmented QRS [fQRS]) on 12-lead electrocardiography have been associated with ventricular arrhythmic events (VAEs) in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to assess the association between new appearances of fQRS and cardiac events in patients with HCM.Methods and Results:The association between baseline fQRS and cardiac events, namely VAEs, heart failure-related hospitalization, and all-cause death, was evaluated retrospectively in 146 HCM patients (46 patients with fQRS, 100 without fQRS). The median follow-up was 5.3 years. Cardiac events occurred in 29 patients with baseline fQRS and 32 patients without baseline fQRS (63% vs. 32%; P<0.001). VAEs occurred in a significantly larger percentage of patients with than without baseline fQRS (54% vs. 23%, respectively; P<0.001). Of the 100 patients without baseline fQRS, 33 had a new appearance of fQRS during the 4.6-year follow-up, whereas 67 did not. VAEs occurred more frequently in the 33 patients with the appearance of fQRS than in those without (42% vs. 13%, respectively; P=0.001). Multivariable analysis showed that the new appearance of fQRS documented before VAEs was associated with VAEs (hazard ratio 4.29, 95% confidence interval 1.81-10.2; P=0.001). CONCLUSIONS: The new appearance of fQRS was associated with an increased risk of VAEs in HCM patients.

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  • Long-term prognosis of patients withJ-wave syndrome. International journal

    Tsukasa Kamakura, Tetsuji Shinohara, Kenji Yodogawa, Nobuyuki Murakoshi, Hiroshi Morita, Naohiko Takahashi, Yasuya Inden, Wataru Shimizu, Akihiko Nogami, Minoru Horie, Takeshi Aiba, Kengo Kusano

    Heart (British Cardiac Society)   106 ( 4 )   299 - 306   2020.2

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    OBJECTIVE: Limited data are currently available regarding the long-term prognosis of patients with J-wave syndrome (JWS). The aim of this study was to investigate the long-term prognosis of patients with JWS and identify predictors of the recurrence of ventricular fibrillation (VF). METHODS: This was a multicentre retrospective study (seven Japanese hospitals) involving 134 patients with JWS (Brugada syndrome (BrS): 85; early repolarisation syndrome (ERS): 49) treated with an implantable cardioverter defibrillator. All patients had a history of VF. All patients with ERS underwent drug provocation testing with standard and high intercostal ECG recordings to rule out BrS. The impact of global J waves (type 1 ECG or anterior J waves and inferolateral J waves in two or more leads) on the prognosis was evaluated. RESULTS: During the 91±66 months of the follow-up period, 52 (39%) patients (BrS: 37; ERS: 15) experienced recurrence of VF. Patients with BrS and ERS with global J waves showed a significantly higher incidence of VF recurrence than those without (BrS: log-rank, p=0.014; ERS: log-rank, p=0.0009). The presence of global J waves was a predictor of VF recurrence in patients with JWS (HR: 2.16, 95% CI 1.21 to 3.91, p=0.0095), while previously reported high-risk electrocardiographic parameters (high-amplitude J waves ≥0.2 mV and J waves associated with a horizontal or descending ST segment) were not predictive of VF recurrence. CONCLUSIONS: This multicentre long-term study showed that the presence of global J waves was associated with a higher incidence of VF recurrence in patients with JWS.

    DOI: 10.1136/heartjnl-2019-315007

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  • Low Consultation Rate of General Population with Atrial Fibrillation.

    Hiroaki Matsumi, Kazufumi Nakamura, Eri Eguchi, Toru Miyoshi, Koji Nakagawa, Nobuhiro Nishii, Atsuyuki Watanabe, Akira Ueoka, Masashi Yoshida, Naoto Tokunaga, Naofumi Amioka, Nobuyuki Yamada, Daiji Saito, Hiroshi Morita, Keiki Ogino, Hiroshi Ito

    International heart journal   60 ( 6 )   1303 - 1307   2019.11

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    In order to prevent ischemic stroke, it is important to identify and treat patients with atrial fibrillation (AF) who do not consult a doctor in a medical institution. The aim of this study was to determine the consultation rate at medical institutions for patients with AF in group medical examinations conducted in a city in western Japan. Of 6101 examinees of group medical examinations (40 years of age or older) conducted in Ibara City, Okayama Prefecture, Japan, from 2012 to 2014, 4338 participants (71.1%) who were evaluated by electrocardiogram (ECG) gave written informed consent and responded to surveys in the form of questionnaires through a personal interview conducted by nurses were included in the Ibara-AF study. A cumulative total of 82 subjects were diagnosed as having AF by ECG (prevalence of AF = 1.89%), and 51 individuals had AF during the three-year period.15 (29.4%) of the 51 patients with AF did not regularly visit medical institutions. Among them, 46.7% (n = 7) and 53.3% (n = 8) of the patients were symptomatic and asymptomatic, respectively, and 73.3% of the patients had a CHADS2 score of more than one point. There were no significant differences in patients' characteristics between regular and non-regular visit groups. In conclusion, about one-third of the patients with AF did not regularly see a doctor in a medical institution and most of them had a CHADS2 score of more than one point in a Japanese rural area. Educating the public about the risks of AF is required.

    DOI: 10.1536/ihj.19-062

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  • Efficacy of catheter ablation for paroxysmal atrial fibrillation in patients with atrial septal defect: a comparison with transcatheter closure alone. International journal

    Koji Nakagawa, Teiji Akagi, Satoshi Nagase, Yoichi Takaya, Yasufumi Kijima, Norihisa Toh, Atsuyuki Watanabe, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Morita, Kengo Kusano, Hiroshi Ito

    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology   21 ( 11 )   1663 - 1669   2019.11

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    AIMS: There is no valid treatment strategy for addressing paroxysmal atrial fibrillation (AF) in patients with unclosed atrial septal defect (ASD). We aimed to assess the efficacy of catheter ablation (CA) compared with transcatheter ASD closure alone for treating pre-existing paroxysmal AF in patients with ASD. METHODS AND RESULTS: Among 908 patients who underwent transcatheter ASD closure, we evaluated 50 consecutive patients (63 ± 12 years) with paroxysmal AF. We compared the AF outcomes of these patients after transcatheter ASD closure between those with and without CA prior to ASD closure. Thirty (60%) patients underwent CA. During the follow-up period after ASD closure (mean: 49 ± 23 months), recurrence of AF was observed in 6/30 (20%) patients with upfront CA and 12/20 (60%) patients with ASD closure alone. Kaplan-Meier analysis showed that the AF-free survival rate was significantly higher for patients with CA than for those with ASD closure alone (79% vs. 37% at 5 years, P = 0.002). Upfront CA and previous heart failure hospitalization were associated with recurrence of AF after ASD closure [hazard ratio (HR) 0.18, 95% confidence interval (CI) 0.06-0.53; P = 0.002 and HR 4.64, 95% CI 1.60-13.49; P = 0.005, respectively]. CONCLUSION: In ASD patient with paroxysmal AF, transcatheter ASD closure alone demonstrated high AF recurrence rate after ASD closure. On the other hand, upfront CA prior to ASD closure substantially suppressed AF recurrence over the long term. A combination of CA and transcatheter ASD closure may be a feasible treatment strategy for paroxysmal AF in patients with ASD.

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  • Open chest epicardial mapping in an asymptomatic patient with Brugada syndrome. International journal

    Atsuyuki Watanabe, Hiroshi Morita, Satoshi Kawada, Motomi Tachibana, Yoshimasa Morimoto, Hiroshi Ito

    HeartRhythm case reports   5 ( 10 )   501 - 504   2019.10

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  • A Low Critical Event Rate Despite a High Abnormal Event Rate in Patients with Cardiac Implantable Electric Devices Followed Up by Remote Monitoring.

    Yoshimasa Morimoto, Nobuhiro Nishii, Saori Tsukuda, Satoshi Kawada, Masakazu Miyamoto, Akihito Miyoshi, Koji Nakagawa, Atsuyuki Watanabe, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    Internal medicine (Tokyo, Japan)   58 ( 16 )   2333 - 2340   2019.8

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    Objective Remote monitoring (RM) of cardiac implantable electric devices (CIEDs) has been advocated as a healthcare standard. However, expert consensus statements suggest that all patients require annual face-to-face follow-up consultations at outpatient clinics even if RM reveals no episodes. The objective of this study was to determine the critical event rate after CIED implantation through RM. Methods This multicenter, retrospective, cohort study evaluated patients with pacemakers (PMs), implantable cardioverter defibrillators (ICDs), or cardiac resynchronization therapy defibrillator (CRT-Ds) and analyzed whether or not the data drawn from RM included abnormal or critical events. Patients A total of 1,849 CIED patients in 12 hospitals who were followed up by the RM center in Okayama University Hospital were included in this study. Results During the mean follow-up period of 774.9 days, 16,560 transmissions were analyzed, of which 11,040 (66.7%) were abnormal events and only 676 (4.1%) were critical events. The critical event rate in the PM group was significantly lower than that in the ICD or CRT-D groups (0.9% vs. 5.0% or 5.9%, p<0.001). A multivariate analysis revealed that ICD, CRT-D, and a low ejection fraction were independently associated with critical events. In patients with ICD, the independent risk factors for a critical event were old age, low ejection fraction, Brugada syndrome, dilated phase hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. Conclusion Although abnormal events were observed in two-thirds of the transmitted RM data, the critical event rate was <1% in patients with a PM, which was lower in comparison to the rates in patients with ICDs or CRT-Ds. A low ejection fraction was an independent predictor of critical events.

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  • Prognosis after lead extraction in patients with cardiac implantable electronic devices infection: Comparison of lead-related infective endocarditis with pocket infection in a Japanese single-center experience.

    Nobuhiro Nishii, Yoshimasa Morimoto, Akihito Miyoshi, Saori Tsukuda, Masakazu Miyamoto, Satoshi Kawada, Koji Nakagawa, Atsuyuki Watanabe, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Morimatsu, Nobuchika Kusano, Shingo Kasahara, Morio Shoda, Hiroshi Ito

    Journal of arrhythmia   35 ( 4 )   654 - 663   2019.8

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    Background: The increase in the use of cardiac implantable electronic devices (CIEDs) has been associated with an increase in CIED-related infections. Transvenous lead extraction is safe and effective for patients with CIED-related infections; however, the mortality rate in these patients is high. The prognosis after transvenous lead extraction in Japanese patients, especially those with lead-related infective endocarditis, has not been evaluated. Then, the purpose of this study is to clarify the prognosis after transvenous lead extraction in Japanese patients with CIED-related infections at a single Japanese center. Methods: A total of 107 patients who underwent transvenous lead extraction were retrospectively reviewed. The patients were divided into a lead-related infective endocarditis group (n = 32) and a pocket infection group (n = 75). Procedure success rate and prognosis after lead extraction were evaluated between the two groups. Results: Procedure success rate was not significantly different between the groups. There were no deaths associated with the procedure or with infection. The survival rate was not significantly different at 1 year or at a median of 816 days (lead-related infective endocarditis vs pocket infection; 93.7% vs 94.7%, P = 1.000; 78.1% vs 81.3%, P = 0.791) Time to reimplantation and duration of hospital stay and antibiotics therapy were significantly longer for patients with lead-related infective endocarditis. Conclusion: In this study, the prognosis for patients with lead-related infective endocarditis after transvenous lead extraction was favorable. Thus, extraction should be strongly recommended, even if the general condition of the patient is poor.

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  • Combination of Renal Angioplasty and Angiotensin-converting-enzyme Inhibitor Can Reduce Proteinuria in Patients with Bilateral Renal Artery Disease.

    Hironobu Toda, Haruhito Uchida, Kazufumi Nakamura, Hidemi Takeuchi, Masaru Kinomura, Koji Nakagawa, Atsuyuki Watanabe, Toru Miyoshi, Nobuhiro Nishii, Hiroshi Morita, Jun Wada, Hiroshi Ito

    Internal medicine (Tokyo, Japan)   58 ( 13 )   1917 - 1922   2019.7

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    Recent large clinical trials failed to show clear benefits of percutaneous transluminal renal angioplasty (PTRA) as compared with medical therapy on patients with renal artery stenosis. It was also reported that proteinuria is an adverse prognostic factor after PTRA, and PTRA is less effective in patients with overt proteinuria. From the renoprotective point of view, to reduce proteinuria after PTRA is an important therapeutic goal in patients with renal artery stenosis with overt proteinuria. We hereby describe two patients successfully treated by combination therapy with PTRA and administration of angiotensin-converting enzyme (ACE) inhibitor for bilateral renal artery disease with overt proteinuria.

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  • Emerging Role of Coronary Computed Tomography Angiography in Lipid-Lowering Therapy: a Bridge to Image-Guided Personalized Medicine. Reviewed International journal

    Toru Miyoshi, Kazuhiro Osawa, Keishi Ichikawa, Kazuki Suruga, Takashi Miki, Masashi Yoshida, Koji Nakagawa, Hironobu Toda, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    Current cardiology reports   21 ( 8 )   72 - 72   2019.6

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    PURPOSE OF REVIEW: To summarize the current status of coronary computed tomography angiography (CTA) in the assessment of coronary plaques and discuss the ability of serial coronary CTA to quantitatively measure changes in the plaque burden in response to lipid-lowering therapy. RECENT FINDINGS: Recent advances in coronary CTA have allowed identification of high-risk coronary features in acute coronary syndrome and measurement of changes in the coronary plaque burden with good reproducibility. Statin therapy may delay plaque progression and change some plaque features. However, the clinical relevance of quantitative changes in coronary plaques and the optimal methods to reduce the plaque burden remain unclear. Despite guideline-directed lipid-lowering therapy, adverse events still occur in substantial numbers of patients receiving statins. Coronary CTA is noninvasive and has high diagnostic performance in patients with coronary artery disease, making change in the plaque burden an applicable biomarker for individualized assessment of future risk.

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  • Successful radiofrequency catheter ablation of a premature ventricular contraction triggering ventricular fibrillation in a patient with short QT syndrome. International journal

    Yoshimasa Morimoto, Atsuyuki Watanabe, Hiroshi Morita, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Ito

    HeartRhythm case reports   5 ( 5 )   262 - 265   2019.5

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  • CLI診療(循環器内科医に求められる役割について) Reviewed

    大塚 寛昭, 戸田 洋伸, 江尻 健太郎, 三好 亨, 中村 一文, 森田 宏, 伊藤 浩

    日本下肢救済・足病学会誌   11 ( 1 )   58 - 58   2019.4

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  • Radiofrequency catheter ablation prior to percutaneous coronary intervention in patients with atrial fibrillation coexisting with stable coronary artery disease: a single-center pilot study.

    Satoshi Kawada, Atsuyuki Watanabe, Yoshimasa Morimoto, Koji Nakagawa, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    Heart and vessels   34 ( 4 )   632 - 640   2019.4

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    Atrial fibrillation (AF) frequently coexists with cardiovascular disease (CAD) in a clinical setting. However, the optimum therapy for AF patients who have concomitant CAD is unclear. We retrospectively examined the efficacy and safety of radiofrequency catheter ablation (RFCA) prior to percutaneous coronary intervention (PCI) in patients with AF who had concomitant stable CAD. Between January 2014 and December 2015, a total 264 patients (179 men; mean age, 65.5 ± 10.1 years) who were referred to undergo a first RFCA procedure were reviewed in this study. Of the 264 patients, 41 (15.5%) had stable CAD detected by multi-detector computed tomography before RFCA. Thirty-seven patients who had AF with stable CAD were divided into two treatment arms: (1) RFCA prior to PCI (n = 13) and (2) PCI prior to RFCA (n = 24) [four patients excluded because of left main coronary artery disease (LMCA) or triple vessel disease (TVD)]. The median follow-up was 14 (IQR 8-19) months. There was no significant difference in AF recurrence rate after the procedure between the RFCA first group and PCI first group (P = 0.515). No symptomatic cardiovascular events occurred the during follow-up period. The PCI first group had a significantly longer duration of triple therapy (188.5 ± 167 days vs 5.6 ± 24.5 days, P = 0.01) and all of the four bleeding events occurred during triple therapy (P = 0.01). The results of this single-center pilot study suggested that prior RFCA in patients with AF coexisting with CAD could have fewer serious bleeding events than prior PCI.

    DOI: 10.1007/s00380-018-1280-8

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  • Association of Genetic and Clinical Aspects of Congenital Long QT Syndrome With Life-Threatening Arrhythmias in Japanese Patients. International journal

    Wataru Shimizu, Hisaki Makimoto, Kenichiro Yamagata, Tsukasa Kamakura, Mitsuru Wada, Koji Miyamoto, Yuko Inoue-Yamada, Hideo Okamura, Kohei Ishibashi, Takashi Noda, Satoshi Nagase, Aya Miyazaki, Heima Sakaguchi, Isao Shiraishi, Takeru Makiyama, Seiko Ohno, Hideki Itoh, Hiroshi Watanabe, Kenshi Hayashi, Masakazu Yamagishi, Hiroshi Morita, Masao Yoshinaga, Yoshiyasu Aizawa, Kengo Kusano, Yoshihiro Miyamoto, Shiro Kamakura, Satoshi Yasuda, Hisao Ogawa, Toshihiro Tanaka, Naotaka Sumitomo, Nobuhisa Hagiwara, Keiichi Fukuda, Satoshi Ogawa, Yoshifusa Aizawa, Naomasa Makita, Tohru Ohe, Minoru Horie, Takeshi Aiba

    JAMA cardiology   4 ( 3 )   246 - 254   2019.3

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    Importance: Long QT syndrome (LQTS) is caused by several ion channel genes, yet risk of arrhythmic events is not determined solely by the responsible gene pathogenic variants. Female sex after adolescence is associated with a higher risk of arrhythmic events in individuals with congenital LQTS, but the association between sex and genotype-based risk of LQTS is still unclear. Objective: To examine the association between sex and location of the LQTS-related pathogenic variant as it pertains to the risk of life-threatening arrhythmias. Design, Setting, and Participants: This retrospective observational study enrolled 1124 genotype-positive patients from 11 Japanese institutions from March 1, 2006, to February 28, 2013. Patients had LQTS type 1 (LQT1), type 2 (LQT2), and type 3 (LQT3) (616 probands and 508 family members), with KCNQ1 (n = 521), KCNH2 (n = 487) and SCN5A (n = 116) genes. Clinical characteristics such as age at the time of diagnosis, sex, family history, cardiac events, and several electrocardiographic measures were collected. Statistical analysis was conducted from January 18 to October 10, 2018. Main Outcomes and Measures: Sex difference in the genotype-specific risk of congenital LQTS. Results: Among the 1124 patients (663 females and 461 males; mean [SD] age, 20 [15] years) no sex difference was observed in risk for arrhythmic events among those younger than 15 years; in contrast, female sex was associated with a higher risk for LQT1 and LQT2 among those older than 15 years. In patients with LQT1, the pathogenic variant of the membrane-spanning site was associated with higher risk of arrhythmic events than was the pathogenic variant of the C-terminus of KCNQ1 (HR, 1.60; 95% CI, 1.19-2.17; P = .002), although this site-specific difference in the incidence of arrhythmic events was observed in female patients only. In patients with LQT2, those with S5-pore-S6 pathogenic variants in KCNH2 had a higher risk of arrhythmic events than did those with others (HR, 1.88; 95% CI, 1.44-2.44; P < .001). This site-specific difference in incidence, however, was observed in both sexes. Regardless of the QTc interval, however, female sex itself was associated with a significantly higher risk of arrhythmic events in patients with LQT2 after puberty (106 of 192 [55.2%] vs 19 of 94 [20.2%]; P < .001). In patients with LQT3, pathogenic variants in the S5-pore-S6 segment of the Nav1.5 channel were associated with lethal arrhythmic events compared with others (HR, 4.2; 95% CI, 2.09-8.36; P < .001), but no sex difference was seen. Conclusions and Relevance: In this retrospective analysis, pathogenic variants in the pore areas of the channels were associated with higher risk of arrhythmic events than were other variants in each genotype, while sex-associated differences were observed in patients with LQT1 and LQT2 but not in those with LQT3. The findings of this study suggest that risk for cardiac events in LQTS varies according to genotype, variant site, age, and sex.

    DOI: 10.1001/jamacardio.2018.4925

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  • 肺癌患者に対する化学放射線療法は大動脈石灰化を増悪させる(Chemoradiation Therapy to Patients with Lung Cancer Exacerbates Aortic Calcification)

    三木 崇史, 三好 亨, 市川 啓之, 宮内 俊策, 宗 淳一, 豊岡 伸一, 中村 一文, 森田 宏, 伊藤 浩

    日本循環器学会学術集会抄録集   83回   OJ33 - 4   2019.3

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  • 2018年の日本循環器学会の遺伝性不整脈の診療に関するガイドラインのBrugada症候群患者のリスク層別化に関する評価(Evaluation of the 2018 Japanese Circulation Society Guidelines of Inherited Arrhythmias for the Risk Stratification in Patients with Brugada Syndrome)

    若宮 輝宜, 鎌倉 令, 篠原 徹二, 淀川 顕司, 村越 伸行, 森田 宏, 高橋 尚彦, 因田 恭也, 清水 渉, 野上 昭彦, 堀江 稔, 中島 健三郎, 片岡 直也, 和田 暢, 山形 研一郎, 石橋 耕平, 井上 優子, 宮本 康二, 永瀬 聡, 野田 崇, 相庭 武司, 安田 聡, 草野 研吾

    日本循環器学会学術集会抄録集   83回   PJ071 - 5   2019.3

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  • SMART pass will prevent inappropriate operation of S-ICD.

    Motomi Tachibana, Nobuhiro Nishii, Kimikazu Banba, Shinpei Fujita, Etsuko Ikeda, Keisuke Okawa, Hiroshi Morita, Hiroshi Ito

    Journal of arrhythmia   35 ( 1 )   86 - 91   2019.2

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    Background: Compared to screening ECG before implantation of a subcutaneous implantable cardioverter-defibrillator (S-ICD), selectable vectors without T-wave oversensing increase after S-ICD implantation. Newer algorithms have recently become available to reduce T-wave oversensing, such as SMART pass (SP). With this function, more selectable vectors are identified after S-ICD implantation. However, this improvement in eligibility utilizing SP has not yet been well validated. We aimed to clarify S-ICD eligibility before and after S-ICD implantation with and without SP. Methods: Participants comprised 34 patients implanted with an S-ICD at Okayama University Hospital and its affiliated hospitals between February 2016 and August 2017. A total of 102 S-ICD vectors were assessed for eligibility before and after S-ICD implantation, at rest and during exercise testing. Vector availability was evaluated in the presence and absence of SP after S-ICD implantation. Results: Subcutaneous implantable cardioverter-defibrillator eligibility was significantly better after implantation even without SP than S-ICD screening before S-ICD implantation, both at rest (before 65.7% vs after 95.1%, P < 0.01) and during exercise (before 59.3% vs after 90.6%, P < 0.01). SP improved S-ICD eligibility during exercise (SP on 97.9% vs off 90.6%, P = 0.03). Multivariate analysis showed the prevalence of S-ICD eligibility increased significantly after S-ICD implantation compared to screening before implantation. SP further increased selectable vectors in multivariate analysis. Conclusion: Available vectors increased significantly after S-ICD implantation compared to preoperative vectors as assessed by S-ICD screening ECG. T-wave oversensing during exercise has been an unresolved issue for S-ICD, but SP will help prevent inappropriate operation with S-ICD.

    DOI: 10.1002/joa3.12141

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  • Gender difference in Brugada syndrome: Mirror images of long QT syndrome? International journal

    Hiroshi Morita

    Heart rhythm   16 ( 2 )   268 - 269   2019.2

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  • Radiofrequency catheter ablation for drug-refractory atrial tachyarrhythmias in a patient with catecholaminergic polymorphic ventricular tachycardia: A case report.

    Satoshi Kawada, Hiroshi Morita, Atsuyuki Watanabe, Hiroshi Ito

    Journal of cardiology cases   19 ( 1 )   36 - 39   2019.1

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    Patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) frequently have atrial arrhythmias, such as atrial tachycardia (AT) and fibrillation (AF), in addition to the ventricular tachyarrhythmias. The development of AT/AF in patients with CPVT is associated with adverse outcomes, and its management is still challenging. A 43-year-old woman with CPVT underwent radiofrequency catheter ablation (RFCA) for drug-refractory AT/AF. Pulmonary vein isolation (PVI) was carried out prior to AT ablation. Repetitive rapid firing from the left superior PV occurred frequently during PVI. After completion of PVI, the firing disappeared, but both polymorphic VT and multifocal ATs were induced by infusion of isoproterenol (ISP) (0.5 mcg/min). The origins of the two ATs were in the right atrium (RA) posterior septum [cycle length (CL), 285 ms] and ostium of the coronary sinus (CS) (CL, 235 ms). Electrophysiologic evaluation revealed that the earliest activation occurred at the RA posterior septum and CS ostium, preceding the onset of P waves by 52 ms and 84 ms, respectively. Application of radiofrequency energy at the site terminated ATs. After RFCA of the two ATs and PVI, no atrial tachyarrhythmias were induced by continuous ISP administration (0.5 mcg/min). <Learning objective: A 43-year-old woman with catecholaminergic polymorphic ventricular tachycardia (CPVT) underwent radiofrequency catheter ablation (RFCA) for drug-refractory atrial tachyarrhythmias (AT/AF). Catecholamine hypersensitivities were observed in the right atrium and pulmonary veins (PVs) as well as the ventricle. Multiple ATs originating from not only a PV but also non-PVs should be considered for elimination of AT/AF in CPVT patients.>.

    DOI: 10.1016/j.jccase.2018.09.004

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  • Percutaneous lead extraction for patients with large vegetations using an unusual technique. International journal

    Nobuhiro Nishii, Akihito Miyoshi, Yoshimasa Morimoto, Hiroshi Morita, Shingo Kasahara, Hiroshi Ito

    HeartRhythm case reports   5 ( 1 )   40 - 43   2019.1

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  • Fontan患者の上室性不整脈に対し、アブレーション、デバイス、薬物療法を行った一例(A case of ablation, pacemaker implantation and medication for supraventricular tachycardia in patient with Fontan operation)

    西井 伸洋, 栄徳 隆裕, 重光 祐輔, 森本 芳正, 浅田 早央莉, 宮本 真和, 杜 徳尚, 中川 晃志, 渡辺 敦之, 森田 宏, 笠原 真悟, 伊藤 浩

    日本成人先天性心疾患学会雑誌   8 ( 1 )   137 - 137   2019.1

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  • Different responses to exercise between Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia. Reviewed

    Inoue YY, Aiba T, Kawata H, Sakaguchi T, Mitsuma W, Morita H, Noda T, Takaki H, Toyohara K, Kanaya Y, Itoi T, Mitsuhashi T, Sumitomo N, Cho Y, Yasuda S, Kamakura S, Kusano K, Miyamoto Y, Horie M, Shimizu W

    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology   20 ( 10 )   1675 - 1682   2018.10

  • Progression of electrocardiographic abnormalities associated with initial ventricular fibrillation in asymptomatic patients with Brugada syndrome. International journal

    Hiroshi Morita, Masakazu Miyamoto, Atsuyuki Watanabe, Saori Tsukuda, Yoshimasa Morimoto, Satoshi Kawada, Koji Nakagawa, Nobuhiro Nishii, Hiroshi Ito

    Heart rhythm   15 ( 10 )   1468 - 1474   2018.10

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    BACKGROUND: Various risk stratifications in asymptomatic patients with Brugada syndrome (BrS) have been proposed, but the electrophysiological change that promotes ventricular fibrillation (VF) is still unknown. OBJECTIVE: The aim of this study was to clarify the changes in electrocardiographic (ECG) markers at the onset of VF from ECGs recorded when patients were still asymptomatic. METHODS: The subjects of this study included 14 patients with VF and 48 consecutive asymptomatic patients with BrS. We compared ECGs before the initial VF events (>6 months; early phase) with ECGs at the initial VF events (late phase). In asymptomatic patients, we evaluated ECGs at 2 time points with an interval of >6 months. We evaluated various ECG markers including type 1 ECG and fragmented QRS (fQRS; multiple spikes within the QRS complex). RESULTS: ECG parameters of the early and late phases were not different except for decreased ST voltage and low incidence of type 1 ECG in asymptomatic patients. There were no differences in ECG parameters of the early phase between patients with VF and asymptomatic patients. In patients with VF, ECGs at the late phase had longer QRS intervals and intervals between the peak and the end of the T wave and more frequent type 1 ECG and fQRS than did ECGs at the early phase. Those changes were associated with initial VF events (QRS widening: odds ratio [OR] 11.5, P < .01; interval between the peak and the end of the T wave: OR 11.6, P < .01; fQRS: odds ratio 15.3, P < .01; type 1 ECG: OR 6.6, P < .05). CONCLUSION: QRS and ST-T wave abnormalities developed in association with the initial VF events. Aggravation of the conduction disturbance in addition to BrS-ECG promotes VF.

    DOI: 10.1016/j.hrthm.2018.06.035

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  • A new approach for implantation of a cardiac resynchronization therapy-defibrillator in a patient with bilateral pectoral neurostimulation devices. International journal

    Saori Tsukuda, Nobuhiro Nishii, Yoshiaki Inoue, Tatsuya Sasaki, Hiroshi Morita, Hiroshi Ito

    HeartRhythm case reports   4 ( 10 )   444 - 446   2018.10

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  • Coral reef aorta一連の病変と考えられた移植腎動脈狭窄に対する血管内治療の1例 Reviewed

    戸田 洋伸, 大塚 寛昭, 江尻 健太郎, 内田 治仁, 杜 徳尚, 中川 晃志, 渡邊 敦之, 三好 亨, 西井 伸洋, 中村 一文, 森田 宏, 伊藤 浩

    脈管学   58 ( Suppl. )   S206 - S206   2018.9

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  • Hot topics in Brugada syndrome. International journal

    Hiroshi Morita

    Heart rhythm   15 ( 9 )   1402 - 1403   2018.9

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  • Corrigendum to "Serum cystatin C levels are associated with coronary artery calcification in women without chronic kidney disease" [J. Cardiol. 70 (2017) 559-564]. International journal

    Hiroyasu Sugiyama, Toru Miyoshi, Kazuhiro Osawa, Takashi Miki, Yuji Koide, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    Journal of cardiology   72 ( 3 )   267 - 268   2018.9

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  • They Are Not Monozygotic Twins - Long QT Syndrome Type 1 (LQT1) and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT).

    Hiroshi Morita

    Circulation journal : official journal of the Japanese Circulation Society   82 ( 9 )   2246 - 2247   2018.8

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  • Shanghai Score System for Diagnosis of Brugada Syndrome: Validation of the Score System and System and Reclassification of the Patients. International journal

    Satoshi Kawada, Hiroshi Morita, Charles Antzelevitch, Yoshimasa Morimoto, Koji Nakagawa, Atsuyuki Watanabe, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Ito

    JACC. Clinical electrophysiology   4 ( 6 )   724 - 730   2018.6

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    OBJECTIVES: The principal objective was to perform an initial test of the Shanghai Brugada Scoring System. Diagnosis of probable and/or definite Brugada syndrome (BrS), possible BrS, and nondiagnostic outcomes were assigned scores of ≥3.5, 2 to 3, and <2 points, respectively. The proposed score system was based on the available published reports and on weighted coefficients derived from limited datasets, with the understanding that these recommendations would need to undergo continuing validation. BACKGROUND: The 2016 HRS/EHRA/APHRS/SOLAECE J-Wave Syndrome Consensus Report proposed a scoring system for diagnosis of BrS that takes into account electrocardiographic recordings, genetic results, clinical characteristics, and family history. METHODS: The patient population consisted of 393 patients evaluated at our hospital for BrS (271 asymptomatic, 99 with syncope, and 23 with ventricular fibrillation [VF]) between 1996 and 2016. Subjects were classified into 4 groups: group A with a score of ≤3.0 points (n = 45); group B with a score of 3.5 points (n = 186); group C with a score of 4.0 to 5.0 points (n = 81); and group D with a score of ≥5.5 points (n = 81). RESULTS: A total of 348 (88%) patients had probable and/or definite BrS, and 81 (20%) had a score ≥5.5. During a follow-up of 97.3 months (range: 39.7 to 142.1 months), 43 patients experienced VF. Significant differences were seen among the 4 groups (p = 0.01). A malignant arrhythmic event did not occur in any patient with possible or nondiagnostic BrS. CONCLUSIONS: This study provided validation for the use of the Shanghai Score System for the diagnosis and risk stratification of patients with BrS.

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  • HCN4-Overexpressing Mouse Embryonic Stem Cell-Derived Cardiomyocytes Generate a New Rapid Rhythm in Rats with Bradycardia.

    Yukihiro Saito, Kazufumi Nakamura, Masashi Yoshida, Hiroki Sugiyama, Makoto Takano, Satoshi Nagase, Hiroshi Morita, Kengo F Kusano, Hiroshi Ito

    International heart journal   59 ( 3 )   601 - 606   2018.5

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    A biological pacemaker is expected to solve the persisting problems of an artificial cardiac pacemaker including short battery life, lead breaks, infection, and electromagnetic interference. We previously reported HCN4 overexpression enhances pacemaking ability of mouse embryonic stem cell-derived cardiomyocytes (mESC-CMs) in vitro. However, the effect of these cells on bradycardia in vivo has remained unclear. Therefore, we transplanted HCN4-overexpressing mESC-CMs into bradycardia model animals and investigated whether they could function as a biological pacemaker. The rabbit Hcn4 gene was transfected into mouse embryonic stem cells and induced HCN4-overexpressing mESC-CMs. Non-cardiomyocytes were removed under serum/glucose-free and lactate-supplemented conditions. Cardiac balls containing 5 × 103 mESC-CMs were made by using the hanging drop method. One hundred cardiac balls were injected into the left ventricular free wall of complete atrioventricular block (CAVB) model rats. Heart beats were evaluated using an implantable telemetry system 7 to 30 days after cell transplantation. The result showed that ectopic ventricular beats that were faster than the intrinsic escape rhythm were often observed in CAVB model rats transplanted with HCN4-overexpressing mESC-CMs. On the other hand, the rats transplanted with non-overexpressing mESC-CMs showed sporadic single premature ventricular contraction but not sustained ectopic ventricular rhythms. These results indicated that HCN4-overexpressing mESC-CMs produce rapid ectopic ventricular rhythms as a biological pacemaker.

    DOI: 10.1536/ihj.17-241

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  • Prognostic Significance of the Sodium Channel Blocker Test in Patients With Brugada Syndrome. International journal

    Akira Ueoka, Hiroshi Morita, Atsuyuki Watanabe, Yoshimasa Morimoto, Satoshi Kawada, Motomi Tachibana, Masakazu Miyamoto, Koji Nakagawa, Nobuhiro Nishii, Hiroshi Ito

    Journal of the American Heart Association   7 ( 10 )   2018.5

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    BACKGROUND: A drug provocation test using a sodium channel blocker (SCB) can unmask a type 1 ECG pattern in patients with Brugada syndrome. However, the prognostic value of the results of an SCB challenge is limited in patients with non-type 1 ECG. We investigated the associations of future risk for ventricular fibrillation with SCB-induced ECG changes and ventricular tachyarrhythmias (VTAs). METHODS AND RESULTS: We administered intravenous pilsicainide to 245 consecutive patients with Brugada syndrome (181 patients with spontaneous type 1 ECG, 64 patients with non-type 1 ECG). ECG parameters before and after the test and occurrence of drug-induced VTAs were evaluated. During a mean follow-up period of 113±57 months, fatal VTA events occurred in 31 patients (sudden death: n=3, ventricular tachycardia/ventricular fibrillation: n=28). Symptomatic patients and spontaneous type 1 ECG were associated with future fatal arrhythmic events. Univariable analysis of ECG parameters after the test showed that long PQ and QRS intervals, high ST level, and SCB-induced VTAs were associated with later VTA events during follow-up. Multivariable analysis showed that symptomatic patients, high ST level (V1) ≥0.3 mV after the test, and SCB-induced VTAs were independent predictors for future fatal arrhythmic events (hazard ratios: 3.28, 2.80, and 3.62, 95% confidence intervals: 1.54-7.47, 1.32-6.35, and 1.64-7.75, respectively; P<0.05). CONCLUSIONS: SCB-induced VTAs and ST-segment augmentation are associated with an increased risk of the development of ventricular tachycardia/ventricular fibrillation events during follow-up in patients with Brugada syndrome.

    DOI: 10.1161/JAHA.118.008617

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  • TRPM4 Mutation in Patients With Ventricular Noncompaction and Cardiac Conduction Disease. International journal

    Yukihiro Saito, Kazufumi Nakamura, Nobuhiro Nishi, Osamu Igawa, Masashi Yoshida, Toru Miyoshi, Atsuyuki Watanabe, Hiroshi Morita, Hiroshi Ito

    Circulation. Genomic and precision medicine   11 ( 5 )   e002103   2018.5

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    DOI: 10.1161/CIRCGEN.118.002103

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  • 開胸マッピングにより右室心外膜側に多彩な異常電位を認めた孤発性無症候Brugada症候群の1例

    渡邊 敦之, 森田 宏, 川田 哲史, 森本 芳正, 橘 元見, 中川 晃志, 西井 伸洋, 中村 一文, 伊藤 浩, 衛藤 弘城, 増田 善逸, 佐野 俊二

    臨床心臓電気生理   41   123 - 126   2018.5

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  • Platypnea-orthodeoxia Syndrome Induced by Multiple Vertebral Compression Fractures and an Atrial Septal Defect.

    Ko Harada, Koji Nakagawa, Hiroaki Ohtsuka, Yoichi Takaya, Teiji Akagi, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

    Internal medicine (Tokyo, Japan)   57 ( 7 )   971 - 973   2018.4

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    Platypnea-orthodeoxia syndrome (POS) is a rare condition that is characterized by dyspnea and arterial oxygen desaturation, which worsen on standing and which are relieved by recumbency. We treated an 80-year-old woman with an atrial septal defect (ASD) who demonstrated POS following thoracic and lumbar vertebral compression fractures. The surgical closure of the ASD relieved her symptoms. The etiology might have been multiple compression fractures causing kyphosis and aortic distortion producing right atrial compression and increased right-to-left flow through the ASD. POS should be considered in the differential diagnosis of patients who develop dyspnea after vertebral compression fractures. The careful assessment of the patient's history and clinical condition helps in the diagnosis of POS.

    DOI: 10.2169/internalmedicine.9904-17

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  • Diastolic Dysfunction Is a Risk of Perioperative Myocardial Injury Assessed by High-Sensitivity Cardiac Troponin T in Elderly Patients Undergoing Non-Cardiac Surgery.

    Hironobu Toda, Kazufumi Nakamura, Koji Nakagawa, Atsuyuki Watanabe, Toru Miyoshi, Nobuhiro Nishii, Kazuyoshi Shimizu, Masao Hayashi, Hiroshi Morita, Hiroshi Morimatsu, Hiroshi Ito

    Circulation journal : official journal of the Japanese Circulation Society   82 ( 3 )   775 - 782   2018.2

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    BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) is useful for detecting myocardial injury and is expected to become a prognostic marker in patients undergoing non-cardiac surgery. The aim of this pilot study evaluating the efficacy of β-blocker therapy in a perioperative setting (MAMACARI study) was to assess perioperative myocardial injury (PMI) in elderly patients with preserved ejection fraction (EF) undergoing non-cardiac surgery.Methods and Results:In this prospective observational cohort study of 151 consecutive patients with preserved EF and aged >60 years who underwent non-cardiac surgery, serum levels of hs-cTnT were measured before and on postoperative days 1 and 3 after surgery. PMI was defined as postoperative hs-cTnT >0.014 ng/mL and relative hs-cTnT change ≥20%. A total of 36 (23.8%) of the patients were diagnosed as having PMI. The incidence of a composite of cardiovascular events within 30 days after surgery, including myocardial infarction, stroke, worsening heart failure, atrial fibrillation and pulmonary embolism, was significantly higher in patients with PMI than in patients without PMI (odds ratio (OR) 9.25, P<0.001, 95% confidence interval (CI) 2.65-32.3). Multivariate analysis revealed that left ventricular diastolic dysfunction defined by echocardiography was independently associated with PMI (OR: 3.029, 95% CI: 1.341-6.84, P=0.008). CONCLUSIONS: PMI is frequently observed in elderly patients undergoing non-cardiac surgery. Diastolic dysfunction is an independent predictor of PMI.

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  • Impact of premature activation of the right ventricle with programmed stimulation in Brugada syndrome. International journal

    Koji Nakagawa, Satoshi Nagase, Hiroshi Morita, Tadashi Wada, Masamichi Tanaka, Masato Murakami, Atsuyuki Watanabe, Nobuhiro Nishii, Kazufumi Nakamura, Kengo F Kusano, Hiroshi Ito, Tohru Ohe

    Journal of cardiovascular electrophysiology   29 ( 1 )   71 - 78   2018.1

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    BACKGROUND: In Brugada syndrome (BrS), it has been reported that delayed activation in the RV is related to the development of type-1 ECG, which is more critical than type-2. On the other hand, the coexistence of complete right bundle-branch block (CRBBB), which also causes delayed activation in the RV, sometimes makes typical BrS ECG misleading. We hypothesized that premature stimulation of the RV can unmask the influence of delayed activation in the RV and convert the morphology of ECG in BrS patients. METHODS AND RESULTS: In 35 BrS patients with type-1 ECG including 8 patients with concomitant CRBBB and 6 control subjects with CRBBB, progressively premature single stimulations were delivered from the RV apex on electrophysiological study. Then we evaluated QRS morphology of fusion beats created by single premature stimulation in each patient. In 29 (83%) of 35 of the BrS patients, conversion from type-1 to type-2 ECG was observed during the process of single premature stimulation. Additionally, in all 8 BrS patients with concomitant CRBBB, type-1 or type-2 BrS ECG was revealed by premature stimulation with relief of CRBBB. These findings were not observed in any of the control subjects with CRBBB. CONCLUSION: Single premature stimulation of the RV converts ECG from type-1 to type-2 in most BrS cases and unmasks type-1 ECG in all BrS cases with CRBBB. Our results could suggest that type-1 ECG is associated with delayed activation of the RV compared with type-2 ECG.

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  • Identification of electrocardiographic risk markers for the initial and recurrent episodes of ventricular fibrillation in patients with Brugada syndrome. International journal

    Hiroshi Morita, Atsuyuki Watanabe, Satoshi Kawada, Masakazu Miyamoto, Yoshimasa Morimoto, Koji Nakagawa, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Ito

    Journal of cardiovascular electrophysiology   29 ( 1 )   107 - 114   2018.1

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    INTRODUCTION: New onset of ventricular fibrillation (VF) in asymptomatic patients with Brugada-type ECG is not frequent, but it cannot be negligible. Risk markers for predicting VF are usually based on results of analysis in symptomatic patients, and they have not been determined for asymptomatic patients. We analyzed ECG markers in patients with Brugada syndrome to differentiate the risk factors for VF in both symptomatic and asymptomatic patients. METHODS: The subjects were 471 patients with Brugada syndrome and we divided the subjects into two groups: Asymptomatic group (n = 326) and Symptomatic group (syncope: n = 122, VF: n = 23). We analyzed the following ECG markers: RR, PQ, QRS, QT and Tpeak-Tend (Tpe) intervals, ST level, atrial fibrillation (AF), atrioventricular block, spontaneous type 1 ECG, early repolarization (ER) and fragmented QRS (fQRS). RESULTS: During follow-up (91 ± 64 months), 41 patients experienced VF (Asymptomatic: n = 10, Symptomatic: n = 31). Univariable analysis showed that spontaneous type 1 ECG, Tpe interval (≥95 milliseconds), high ST level (≥0.52 mV) and fQRS were common predictors for VF in both the Asymptomatic and Symptomatic groups. In addition to the common risk factors, wide QRS (≥107 milliseconds), long QT interval (≥420 milliseconds), ER and AF were predictors for VF in Symptomatic group. Multivariable analysis of the Symptomatic group showed fQRS, Tpe and ER were independent predictors of prognosis. CONCLUSIONS: fQRS and Tpe interval are common risk factors for VF in both asymptomatic and symptomatic patients, whereas ER is a predictor for recurrent VF.

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  • Exercise stress test reveals ineligibility for subcutaneous implantable cardioverter defibrillator in patients with Brugada syndrome. International journal

    Motomi Tachibana, Nobuhiro Nishii, Hiroshi Morita, Koji Nakagawa, Atsuyuki Watanabe, Kazufumi Nakamura, Hiroshi Ito

    Journal of cardiovascular electrophysiology   28 ( 12 )   1454 - 1459   2017.12

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    BACKGROUND: The eligibility of patients with Brugada syndrome (BrS) for implantation of a subcutaneous implantable cardioverter defibrillator (S-ICD) is not well known. This study aimed to clarify the eligibility of BrS patients for S-ICD using electrocardiography (ECG) at rest and during exercise testing. We also analyzed factors associated with ineligibility for S-ICD from standard 12-lead ECG at rest. METHODS: We enrolled 110 consecutive BrS patients who visited Okayama university hospital from December 2015 to December 2016. All patients were assessed for S-ICD eligibility, which required one lead to satisfy the S-ICD screening template. We assessed standard 12-lead ECG parameters in all participants. Of those who passed S-ICD screening, 45 patients were assessed for S-ICD eligibility during treadmill stress test. RESULTS: Mean age of study patients was 54 ± 13 years and 108 (98%) were men. In total, 89 patients (81%) satisfied S-ICD indications at rest. Existence of complete right bundle branch block (CRBBB) on standard 12-lead ECG was a significant predictor of ineligibility for S-ICD (odds ratio, 5.00; P = 0.03; 95%CI, 1.14-21.98). Of the 45 patients who underwent treadmill stress testing, 11 patients (24%) showed ineligibility for S-ICD during the test. CONCLUSION: CRBBB was a predictor of ineligibility for S-ICD in patients with BrS. Sinus tachycardia changes ECG morphology in some patients and stress testing should be considered before S-ICD implantation.

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  • 顕性蛋白尿をきたした腎動脈狭窄症に対するPTRAの腎保護効果についての検討 Reviewed

    戸田 洋伸, 内田 治仁, 竹内 英実, 江尻 健太郎, 大塚 寛昭, 中川 晃志, 渡邊 敦之, 西井 伸洋, 三好 亨, 中村 一文, 森田 宏, 和田 淳, 伊藤 浩

    脈管学   57 ( Suppl. )   S138 - S138   2017.10

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  • 左冠動脈主幹部に起始異常を認め、その物理的圧迫による心筋虚血にて数年間にわたり失神を繰り返した若年者の1症例

    網岡 尚史, 渡邊 敦之, 大塚 寛昭, 赤木 達, 麻植 浩樹, 中川 晃志, 中村 一文, 森田 宏, 小谷 恭弘, 新井 禎彦, 笠原 真悟, 佐野 俊二, 伊藤 浩

    心臓   49 ( Suppl.1 )   110 - 110   2017.8

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  • Recording of isolated very delayed potentials on the right ventricular epicardium in a patient with Brugada syndrome. International journal

    Atsuyuki Watanabe, Hiroshi Morita, Sho Tsushima, Koji Nakagawa, Nobuhiro Nishii, Hiroshi Ito

    HeartRhythm case reports   3 ( 7 )   344 - 347   2017.7

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  • Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry. International journal

    Kenichiro Yamagata, Minoru Horie, Takeshi Aiba, Satoshi Ogawa, Yoshifusa Aizawa, Tohru Ohe, Masakazu Yamagishi, Naomasa Makita, Harumizu Sakurada, Toshihiro Tanaka, Akihiko Shimizu, Nobuhisa Hagiwara, Ryoji Kishi, Yukiko Nakano, Masahiko Takagi, Takeru Makiyama, Seiko Ohno, Keiichi Fukuda, Hiroshi Watanabe, Hiroshi Morita, Kenshi Hayashi, Kengo Kusano, Shiro Kamakura, Satoshi Yasuda, Hisao Ogawa, Yoshihiro Miyamoto, Jamie D Kapplinger, Michael J Ackerman, Wataru Shimizu

    Circulation   135 ( 23 )   2255 - 2270   2017.6

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    BACKGROUND: The genotype-phenotype correlation of SCN5A mutations as a predictor of cardiac events in Brugada syndrome remains controversial. We aimed to establish a registry limited to probands, with a long follow-up period, so that the genotype-phenotype correlation of SCN5A mutations in Brugada syndrome can be examined without patient selection bias. METHODS: This multicenter registry enrolled 415 probands (n=403; men, 97%; age, 46±14 years) diagnosed with Brugada syndrome whose SCN5A gene was analyzed for mutations. RESULTS: During a mean follow-up period of 72 months, the overall cardiac event rate was 2.5%/y. In comparison with probands without mutations (SCN5A (-), n=355), probands with SCN5A mutations (SCN5A (+), n=60) experienced their first cardiac event at a younger age (34 versus 42 years, P=0.013), had a higher positive rate of late potentials (89% versus 73%, P=0.016), exhibited longer P-wave, PQ, and QRS durations, and had a higher rate of cardiac events (P=0.017 by log-rank). Multivariate analysis indicated that only SCN5A mutation and history of aborted cardiac arrest were significant predictors of cardiac events (SCN5A (+) versus SCN5A (-): hazard ratio, 2.0 and P=0.045; history of aborted cardiac arrest versus no such history: hazard ratio, 6.5 and P<0.001). CONCLUSIONS: Brugada syndrome patients with SCN5A mutations exhibit more conduction abnormalities on ECG and have higher risk for cardiac events.

    DOI: 10.1161/CIRCULATIONAHA.117.027983

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  • Epicardially placed implantable cardioverter-defibrillator for a child with congenital long QT syndrome.

    Hirotaro Sugiyama, Motomi Tachibana, Hiroshi Morita, Nobuhiro Nishii, Akihito Miyoshi, Hiroyasu Sugiyama, Koji Nakagawa, Atsuyuki Watanabe, Kazufumi Nakamura, Hiroshi Ito

    Journal of arrhythmia   33 ( 3 )   237 - 239   2017.6

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    A 7-year-old boy presented at our hospital with syncope. At birth, electrocardiography had shown a long QT interval with torsade de pointes (TdP). Congenital long QT syndrome (LQTS) had been diagnosed by genetic testing, and was successfully controlled with oral propranolol. At age 7, TdP had recurred with syncope. Electrocardiography revealed a prominent long QT interval with T-wave alternans. The propranolol dose was increased, but TdP remained uncontrolled. A cardioverter-defibrillator (ICD) was implanted epicardially, and TdP completely resolved with atrial pacing. We report this rare case of ICD implantation in a child with LQTS.

    DOI: 10.1016/j.joa.2016.10.561

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  • J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge. International journal

    Charles Antzelevitch, Gan-Xin Yan, Michael J Ackerman, Martin Borggrefe, Domenico Corrado, Jihong Guo, Ihor Gussak, Can Hasdemir, Minoru Horie, Heikki Huikuri, Changsheng Ma, Hiroshi Morita, Gi-Byoung Nam, Frederic Sacher, Wataru Shimizu, Sami Viskin, Arthur A M Wilde

    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology   19 ( 4 )   665 - 694   2017.4

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  • Distribution and Prognostic Significance of Fragmented QRS in Patients With Brugada Syndrome. International journal

    Hiroshi Morita, Atsuyuki Watanabe, Yoshimasa Morimoto, Satoshi Kawada, Motomi Tachibana, Koji Nakagawa, Nobuhiro Nishii, Hiroshi Ito

    Circulation. Arrhythmia and electrophysiology   10 ( 3 )   2017.3

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    BACKGROUND: Fragmented QRS complexes (fQRS) in the right precordial leads are associated with occurrence of ventricular fibrillation (VF) in Brugada syndrome. Recently, epicardial mapping has revealed abnormal electrograms at the right ventricular (RV) outflow tract and inferior region of the right ventricle. fQRS may reflect the extent of the area of abnormal potentials, but whether the distribution of fQRS has prognostic value is not known. METHODS AND RESULTS: We evaluated the existence of fQRS in 456 patients with Brugada syndrome, including 117 patients with syncope and 23 patients with VF. The region of fQRS was defined as inferior (II, III, and aVF), lateral (I, aVL, and V5 and V6), anterior (V3 and V4), RV (V1 and V2), and RV outflow tract (V1 and V2 at the third intercostal space). fQRS were present in 229 patients (RV outflow tract in 175, inferior in 135, RV in 90, and lateral in 16 patients). During follow-up (mean 91 months), 39 patients experienced VF. In univariable analyses, fQRS in any distribution and fQRS in each region excluding the RV were associated with VF. Multivariable analysis showed that fQRS in the inferior (hazard ratio, 3.9; confidence interval, 1.9-8.5), lateral (hazard ratio, 3.5; confidence interval, 1.2-8.2), and RV outflow tract (hazard ratio, 2.5; confidence interval, 1.2-5.6) were associated with VF events. The presence of multiple regions of fQRS was associated with worse prognosis. CONCLUSIONS: The distribution of fQRS is associated with prognosis in Brugada syndrome, further supporting the association of fQRS and arrhythmia substrate.

    DOI: 10.1161/CIRCEP.116.004765

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  • Local Left Ventricular Epicardial J Waves and Late Potentials in Brugada Syndrome Patients with Inferolateral Early Repolarization Pattern. International journal

    Satoshi Nagase, Masamichi Tanaka, Hiroshi Morita, Koji Nakagawa, Tadashi Wada, Masato Murakami, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Ito, Tohru Ohe, Kengo F Kusano

    Frontiers in physiology   8   14 - 14   2017

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    Background: Brugada syndrome (BrS) is characterized by J-point or ST-segment elevation on electrocardiograms (ECGs) and increased risk of ventricular fibrillation (VF). In BrS, epicardial depolarization abnormality with delayed potential on the right ventricular outflow tract is reportedly the predominant mechanism underlying VF. Yet VF occurrence is also associated with early repolarization (ER) pattern in the inferolateral ECG leads, which may represent the inferior and/or left lateral ventricular myocardium. The aim of this study was to examine epicardial electrograms recorded directly at the left ventricle (LV) in BrS patients after VF episodes. Methods: In 12 BrS patients who had experienced VF episodes and 17 control subjects, a multipolar catheter was introduced into the left lateral coronary vein for unipolar and bipolar electrogram recordings at the LV epicardium. Both inferior and lateral ER patterns on ECG were observed in three BrS patients and six control subjects. Results: In the epicardium, prominent J waves were detected using unipolar recording, and potentials after the QRS complex were detected using bipolar recording in three of the 12 BrS patients. These three patients also showed both inferior and lateral ER patterns on ECG. Neither prominent J waves nor potentials after the QRS complex were recorded at the endocardium of the LV in any of these three patients; nor were they seen at the epicardium in any of the control subjects. These features were accentuated on pilsicainide administration (n = 2) but diminished on constant atrial pacing (n = 3) and isoproterenol administration (n = 1). The J waves observed through unipolar recording coincided with the potentials after QRS complex observed through bipolar recording and with the inferolateral ER patterns on ECG. Conclusions: We recorded prominent J waves in unipolar electrogram and potentials after QRS complex in bipolar electrogram at the LV epicardium in BrS patients with global ER pattern. The prominent J waves coincided with the potentials after QRS complex and the inferolateral ER pattern on ECG. The characteristics of the inferolateral ER pattern on ECG in these patients primarily represent depolarization feature.

    DOI: 10.3389/fphys.2017.00014

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  • J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge.

    Charles Antzelevitch, Gan-Xin Yan, Michael J Ackerman, Martin Borggrefe, Domenico Corrado, Jihong Guo, Ihor Gussak, Can Hasdemir, Minoru Horie, Heikki Huikuri, Changsheng Ma, Hiroshi Morita, Gi-Byoung Nam, Frederic Sacher, Wataru Shimizu, Sami Viskin, Arthur A M Wilde

    Journal of arrhythmia   32 ( 5 )   315 - 339   2016.10

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  • J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge. International journal

    Charles Antzelevitch, Gan-Xin Yan, Michael J Ackerman, Martin Borggrefe, Domenico Corrado, Jihong Guo, Ihor Gussak, Can Hasdemir, Minoru Horie, Heikki Huikuri, Changsheng Ma, Hiroshi Morita, Gi-Byoung Nam, Frederic Sacher, Wataru Shimizu, Sami Viskin, Arthur A M Wilde

    Heart rhythm   13 ( 10 )   e295-324   2016.10

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    DOI: 10.1016/j.hrthm.2016.05.024

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  • 冠動脈ハイリスクプラークの予測におけるトリグリセリド/HDLコレステロール比の有用性について Reviewed

    三木 崇史, 三好 亨, 小出 祐嗣, 江尻 健太郎, 戸田 洋伸, 吉田 雅言, 中村 一文, 森田 宏, 伊藤 浩

    日本心臓病学会学術集会抄録   64回   P - 116   2016.9

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  • Activation Pattern of the Polymorphic Ventricular Tachycardia and Ventricular Fibrillation on Body Surface Mapping in Patients With Brugada Syndrome.

    Akira Ueoka, Hiroshi Morita, Atsuyuki Watanabe, Koji Nakagawa, Nobuhiro Nishii, Satoshi Nagase, Tohru Ohe, Hiroshi Ito

    Circulation journal : official journal of the Japanese Circulation Society   80 ( 8 )   1734 - 43   2016.7

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    BACKGROUND: Clinical and experimental studies have shown the existence of an arrhythmogenic substrate in the right ventricular outflow tract (RVOT) in patients with Brugada syndrome (BrS). To evaluate the importance of the RVOT, we evaluated the activation pattern of induced ventricular tachyarrhythmias using body surface mapping (BSM) in patients with BrS. METHODS AND RESULTS: We examined 14 patients with BrS in whom ventricular tachyarrhythmias were induced by programmed electrical stimulation. The 87-lead BSM was recorded during induced ventricular tachyarrhythmias, and an activation map and an isopotential map of QRS complexes every 5 ms were constructed to evaluate the activation pattern of ventricular tachyarrhythmias. BSM during 20 episodes of ventricular tachyarrhythmias induced at the RVOT showed that repetitive excitation was generated at the RVOT and propagated to the inferior RV and left ventricle, and then returned to the RVOT. Polymorphic QRS change during ventricular tachyarrhythmias was associated with migration of the earliest activation site and rotor. BSM during 4 episodes of ventricular fibrillation (VF) showed that the excitation front moved randomly with formation of multiple wavefronts. CONCLUSIONS: Programmed stimulation initiated repetitive firing from the RVOT. Migration and competition of the earliest activation site and rotor and local conduction delay changed the QRS morphology. Degeneration of the reentrant circuit into multiple wavefronts resulted in VF. (Circ J 2016; 80: 1734-1743).

    DOI: 10.1253/circj.CJ-16-0124

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  • Prognostic significance of fever-induced Brugada syndrome. International journal

    Yuka Mizusawa, Hiroshi Morita, Arnon Adler, Ofer Havakuk, Aurélie Thollet, Philippe Maury, Dao W Wang, Kui Hong, Estelle Gandjbakhch, Frédéric Sacher, Dan Hu, Ahmad S Amin, Najim Lahrouchi, Hanno L Tan, Charles Antzelevitch, Vincent Probst, Sami Viskin, Arthur A M Wilde

    Heart rhythm   13 ( 7 )   1515 - 20   2016.7

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    BACKGROUND: In Brugada syndrome (BrS), spontaneous type 1 electrocardiogram (ECG) is an established risk marker for fatal arrhythmias whereas drug-induced type 1 ECG shows a relatively benign prognosis. No study has analyzed the prognosis of fever-induced type 1 ECG (F-type1) in a large BrS cohort. OBJECTIVES: The objectives of this study were to assess the prognosis of F-type1 in asymptomatic BrS and to compare the effects of fever and drugs on ECG parameters. METHODS: One hundred twelve patients with BrS who developed F-type1 were retrospectively enrolled. Prognosis was evaluated in 88 asymptomatic patients. In a subgroup (n = 52), ECG parameters of multiple ECGs (at baseline, during fever, and after drug challenge) were analyzed. RESULTS: Eighty-eight asymptomatic patients had a mean age of 45.8 ± 18.7 years, and 71.6% (67 of 88) were men. Twenty-one percent (18 of 88) had a family history of sudden cardiac death, and 26.4% (14 of 53) carried a pathogenic SCN5A mutation. Drug challenge was positive in 29 of 36 patients tested (80.6%). The risk of ventricular fibrillation in asymptomatic patients was 0.9%/y (3 of 88; 43.6 ± 37.4 months). ST-segment elevation in lead V2 during fever and after drug challenge was not significantly different (0.41 ± 0.21 ms during fever and 0.40 ± 0.30 ms after drug challenge; P > .05). Fever shortened the PR interval compared to baseline, whereas drug challenge resulted in prolonged PR interval and QRS duration (PR interval: 169 ± 29 ms at baseline, 148 ± 45 ms during fever, and 202 ± 35 ms after drug challenge; QRS duration: 97 ± 18 ms at baseline, 92 ± 28 ms during fever, and 117 ± 21 ms after drug challenge). CONCLUSION: Patients with BrS who develop F-type1 are at risk of arrhythmic events. F-type1 appears to develop through a more complex mechanism as compared with drug-induced type 1 ECG.

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  • Fallot四徴症術後遠隔期にカテコラミン誘発性多形性心室頻拍が疑われICD植込みを行った1例

    上岡 亮, 森田 宏, 西井 伸洋, 橘 元見, 津島 翔, 中川 晃志, 渡邊 敦之, 中村 一文, 永徳 隆裕, 馬場 健児, 大月 審一, 笠原 真吾, 佐野 俊二, 永瀬 聡, 伊藤 浩

    心臓   48 ( 1 )   S1_163 - S1_163   2016

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    <p> 症例は3歳の男児. 生後6カ月でFallot四徴症 (TOF) に対し修復術施行, 術後高度肺動脈弁逆流 (PR) が残存し加療中であった.</p><p> 三輪車に乗っている際に心肺停止状態となり, 救急搬送された. 初期波形は心室細動であり, 電気的除細動器により停止するも, 啼泣および興奮時に繰り返し二方向性の心室頻拍 (VT) をきたした. β遮断薬・Ⅰ群薬での治療を試みたが発作抑制されず, 徐脈も著明となり増量困難であった.</p><p> 心臓電気生理検査では瘢痕は見られず, プログラム刺激でVTは誘発されず, カテコラミン負荷で多源性VTが誘発された. VTは手術切開線と関連無く, 交感神経亢進時に誘発される二方向性VTで, カテコラミン誘発性多形性心室頻拍 (CPVT) と診断. 薬物治療は限界で高度PRもあり, 開胸下で右室流出路再建術, ICD心外膜リード植込みを行った. 心房ペーシング下でのβ遮断薬内服で, VTの再発は見られていない.</p><p> TOFにCPVTが合併した稀有な症例を経験したので報告する.</p>

    DOI: 10.11281/shinzo.48.S1_163

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  • Incidence and Clinical Significance of Brugada Syndrome Masked by Complete Right Bundle-Branch Block.

    Tadashi Wada, Satoshi Nagase, Hiroshi Morita, Koji Nakagawa, Nobuhiro Nishii, Kazufumi Nakamura, Kunihisa Kohno, Hiroshi Ito, Kengo F Kusano, Tohru Ohe

    Circulation journal : official journal of the Japanese Circulation Society   79 ( 12 )   2568 - 75   2015

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    BACKGROUND: Brugada syndrome (BrS)-type electrocardiogram (ECG) is concealed by complete right bundle-branch block (CRBBB) in some cases of BrS. Clinical significance of BrS masked by CRBBB is not well known. METHODS AND RESULTS: We reviewed an ECG database of 326 BrS patients who had type 1 ECG with or without pilsicainide. "BrS masked by CRBBB" was defined on ECG as <2-mm elevation of the J point at the time of CRBBB in the right precordial leads, and BrS-type J-point elevation ≥2 mm at the time of normalized QRS complex on relieved CRBBB. We identified 25 BrS patients (7.7%) with persistent (n=12) or intermittent CRBBB (n=13). Relief of CRBBB by pacing was performed in patients with persistent CRBBB. The prevalence of BrS masked by CRBBB was 3.1% (10/326 patients). Three patients had type 1 ECG, and 7 patients had type 2 or 3 ECG on relief of CRBBB. Two of these 10 patients had lethal arrhythmic events during the follow-up period (mean, 86.4±57.2 months). There was no prognostic difference between BrS masked by CRBBB and other BrS. CONCLUSIONS: In a small BrS population, CRBBB can completely mask typical BrS-type ECG. BrS masked by CRBBB is associated with the same risk of fatal ventricular tachyarrhythmia as other BrS.

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  • Risk stratification in patients with Brugada syndrome without previous cardiac arrest – prognostic value of combined risk factors.

    Hideo Okamura, Tsukasa Kamakura, Hiroshi Morita, Koji Tokioka, Ikutaro Nakajima, Mitsuru Wada, Kohei Ishibashi, Koji Miyamoto, Takashi Noda, Takeshi Aiba, Nobuhiro Nishii, Satoshi Nagase, Wataru Shimizu, Satoshi Yasuda, Hisao Ogawa, Shiro Kamakura, Hiroshi Ito, Tohru Ohe, Kengo F Kusano

    Circulation journal : official journal of the Japanese Circulation Society   79 ( 2 )   310 - 7   2015

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    BACKGROUND: Risk stratification in patients with Brugada syndrome for primary prevention of sudden cardiac death is still an unsettled issue. A recent consensus statement suggested the indication of implantable cardioverter defibrillator (ICD) depending on the clinical risk factors present (spontaneous type 1 Brugada electrocardiogram (ECG) [Sp1], history of syncope [syncope], and ventricular fibrillation during programmed electrical stimulation [PES+]). The indication of ICD for the majority of patients, however, remains unclear. METHODS AND RESULTS: A total of 218 consecutive patients (211 male; aged 46 ± 13 years) with a type 1 Brugada ECG without a history of cardiac arrest who underwent evaluation for ICD including electrophysiological testing were examined retrospectively. During a mean follow-up period of 78 months, 26 patients (12%) developed arrhythmic events. On Kaplan-Meier analysis patients with each of Sp1, syncope, or PES+ suffered arrhythmic events more frequently (P=0.018, P<0.001, and P=0.003, respectively). On multivariate analysis Sp1 and syncope were independent predictors of arrhythmic events. When dividing patients according to the number of these 3 risk factors present, patients with 2 or 3 risk factors experienced arrhythmic events more frequently than those with 0 or 1 risk factor (23/93 vs. 3/125; P<0.001). CONCLUSIONS: Syncope, Sp1, and PES+ are important risk factors and the combination of these risks well stratify the risk of later arrhythmic events.

    DOI: 10.1253/circj.CJ-14-1059

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  • Electrocardiographic parameters and fatal arrhythmic events in patients with Brugada syndrome: combination of depolarization and repolarization abnormalities. International journal

    Koji Tokioka, Kengo F Kusano, Hiroshi Morita, Daiji Miura, Nobuhiro Nishii, Satoshi Nagase, Kazufumi Nakamura, Kunihisa Kohno, Hiroshi Ito, Tohru Ohe

    Journal of the American College of Cardiology   63 ( 20 )   2131 - 2138   2014.5

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    OBJECTIVES: This study aimed to determine the usefulness of the combination of several electrocardiographic markers on risk assessment of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS). BACKGROUND: Detection of high-/low-risk BrS patients using a noninvasive method is an important issue in the clinical setting. Several electrocardiographic markers related to depolarization and repolarization abnormalities have been reported, but the relationship and usefulness of these parameters in VF events are unclear. METHODS: Baseline characteristics of 246 consecutive patients (236 men; mean age, 47.6 ± 13.6 years) with a Brugada-type electrocardiogram, including 13 patients with a history of VF and 40 patients with a history of syncope episodes, were retrospectively analyzed. During the mean follow-up period of 45.1 months, VF in 23 patients and sudden cardiac death (SCD) in 1 patient were observed. Clinical/genetic and electrocardiographic parameters were compared with VF/SCD events. RESULTS: On univariate analysis, a history of VF and syncope episodes, paroxysmal atrial fibrillation, spontaneous type 1 pattern in the precordial leads, and electrocardiographic markers of depolarization abnormalities (QRS duration ≥120 ms, and fragmented QRS [f-QRS]) and those of repolarization abnormalities (inferolateral early repolarization [ER] pattern and QT prolongation) were associated with later cardiac events. On multivariable analysis, a history of VF and syncope episodes, inferolateral ER pattern, and f-QRS were independent predictors of documented VF and SCD (odds ratios: 19.61, 28.57, 2.87, and 5.21, respectively; p < 0.05). Kaplan-Meier curves showed that the presence/absence of inferolateral ER and f-QRS predicted a worse/better prognosis (log-rank test, p < 0.01). CONCLUSIONS: The combination of depolarization and repolarization abnormalities in BrS is associated with later VF events. The combination of these abnormalities is useful for detecting high- and low-risk BrS patients.

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  • Left ventricular epicardial electrogram recordings in idiopathic ventricular fibrillation with inferior and lateral early repolarization. International journal

    Koji Nakagawa, Satoshi Nagase, Hiroshi Morita, Hiroshi Ito

    Heart rhythm   11 ( 2 )   314 - 7   2014.2

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    DOI: 10.1016/j.hrthm.2013.10.057

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  • A successful epicardial ablation from the middle cardiac vein for ventricular tachycardia with prior inferior myocardial infarction

    Wada Tadashi, Nagase Satoshi, Tanaka Masamichi, Nakagawa Koji, Nishii Hironobu, Kohno Yoshihisa, Nakamura Kazufumi, Morita Hiroshi, Ito Hiroshi

    Shinzo   46 ( 3 )   S3_203 - S3_211   2014

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    DOI: 10.11281/shinzo.46.S3_203

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  • LQT1において血清カリウム値がQT間隔および不整脈イベントに及ぼす影響

    杉山 洋樹, 中村 一文, 森田 宏, 三浦 大志, 永瀬 聡, 河野 晋久, 草野 研吾, 大江 透, 伊藤 浩

    心電図   33 ( Suppl.4 )   S - 194   2013.9

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  • Prognostic significance of early repolarization in inferolateral leads in Brugada patients with documented ventricular fibrillation: a novel risk factor for Brugada syndrome with ventricular fibrillation. International journal

    Hiro Kawata, Hiroshi Morita, Yuko Yamada, Takashi Noda, Kazuhiro Satomi, Takeshi Aiba, Mitsuaki Isobe, Satoshi Nagase, Kazufumi Nakamura, Kengo Fukushima Kusano, Hiroshi Ito, Shiro Kamakura, Wataru Shimizu

    Heart rhythm   10 ( 8 )   1161 - 8   2013.8

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    BACKGROUND: Little is known about the clinical and prognostic impact of early repolarization (ER) on patients with Brugada syndrome (BrS), especially those with documented ventricular fibrillation (VF). OBJECTIVE: To investigate the prevalence and prognostic significance of ER in inferolateral leads in patients with BrS and documented VF. METHODS: We investigated 10 different 12-lead electrocardiograms (ECGs) recorded on different days to identify the presence of ER, which was defined as J-point elevation ≥0.1 mV in inferior (II, III, aVF) or lateral leads (I, aVL, V₄-V₆), in 49 individuals (46 men; age 46 ± 13 years) with a type 1 ECG of BrS and previous history of VF. RESULTS: ER was observed persistently (in all ECGs) in 15 patients (31%; P group), intermittently (in at least one but not in all ECGs) in 16 patients (33%; I group), and not observed in 18 patients (37%; N group), yielding an overall ER incidence of 63% (31/49). During the follow-up period (7.7 years), recurrence of VF was documented in all 15 patients (100%) in the P group, and less in 12 patients (75%) in the I group and in 8 patients (44%) in the N group. The P group showed a worse prognosis than N group (P = .0001) by Kaplan-Meier analysis. Either persistent or intermittent ER in an inferolateral lead was an independent predictor of fatal arrhythmic events (hazard ratio 4.88, 95% confidence interval 2.02-12.7, P = .0004; and hazard ratio 2.50, 95% confidence interval 1.03-6.43, P = .043, respectively). CONCLUSION: The prevalence of ER in inferolateral leads was high and an especially persistent form of ER was associated with a worse outcome in BrS patients with documented VF.

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  • Ion channel complex disease in long QT syndrome. International journal

    Hiroshi Morita

    Heart rhythm   10 ( 5 )   738 - 9   2013.5

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  • Alogliptin ameliorates postprandial lipemia and postprandial endothelial dysfunction in non-diabetic subjects: a preliminary report Reviewed

    Yoko Noda, Toru Miyoshi, Hiroki Oe, Yuko Ohno, Kazufumi Nakamura, Norihisa Toh, Kunihisa Kohno, Hiroshi Morita, Kengo Kusano, Hiroshi Ito

    CARDIOVASCULAR DIABETOLOGY   12   8   2013.1

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    Background: Postprandial hyperlipidemia impairs endothelial function and participates in the development of atherosclerosis. We investigated the postprandial effects of a dipeptidyl peptidase IV inhibitor, alogliptin, on endothelial dysfunction and the lipid profile.
    Methods: A randomized cross-over trial design in 10 healthy volunteers (8 males and 2 females, 35 +/- 10 years) was performed. The postprandial effects before and after a 1-week treatment of 25 mg/day alogliptin on endothelial function were assessed with brachial artery flow-mediated dilation (FMD) and changing levels of lipids, apolipoprotein B48 (apoB-48), glucose, glucagon, insulin, and glucagon-like peptide-1 (GLP-1) during fasting and at 2, 4, 6, and 8 h after a standard meal loading test.
    Results: Alogliptin treatment significantly suppressed the postprandial elevation in serum triglyceride (incremental area under the curve [AUC]; 279 +/- 31 vs. 182 +/- 32 mg h/dl, p = 0.01), apoB-48 (incremental AUC; 15.4 +/- 1.7 vs. 11.7 +/- 1.1 mu g h/ml, p = 0.04), and remnant lipoprotein cholesterol (RLP-C) (incremental AUC: 29.3 +/- 3.2 vs. 17.6 +/- 3.3 mg h/dl, p = 0.01). GLP-1 secretion was significantly increased after alogliptin treatment. Postprandial endothelial dysfunction (maximum decrease in% FMD, from -4.2 +/- 0.5% to -2.6 +/- 0.4%, p = 0.03) was significantly associated with the maximum change in apoB-48 (r = -0.46, p = 0.03) and RLP-C (r = -0.45, p = 0.04).
    Conclusion: Alogliptin significantly improved postprandial endothelial dysfunction and postprandial lipemia, suggesting that alogliptin may be a promising anti-atherogenic agent.

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  • Increased passive stiffness of cardiomyocytes in the transverse direction and residual actin and myosin cross-bridge formation in hypertrophied rat hearts induced by chronic β-adrenergic stimulation.

    Wakako Sumita Yoshikawa, Kazufumi Nakamura, Daiji Miura, Juichiro Shimizu, Ken Hashimoto, Noriyuki Kataoka, Hiroko Toyota, Hiroshi Okuyama, Toru Miyoshi, Hiroshi Morita, Kengo Fukushima Kusano, Tatsuhito Matsuo, Miyako Takaki, Fumihiko Kajiya, Naoto Yagi, Tohru Ohe, Hiroshi Ito

    Circulation journal : official journal of the Japanese Circulation Society   77 ( 3 )   741 - 8   2013

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    BACKGROUND: Left ventricular (LV) hypertrophy is often present in patients with diastolic heart failure. However, stiffness of hypertrophied cardiomyocytes in the transverse direction has not been fully elucidated. The aim of this study was to assess passive cardiomyocyte stiffness of hypertrophied hearts in the transverse direction and the influence of actin-myosin cross-bridge formation on the stiffness. METHODS AND RESULTS: Wistar rats received a vehicle (control) or isoproterenol (ISO) subcutaneously. After 7 days, compared with the controls, ISO administration had significantly increased heart weight and LV wall thickness and had decreased peak early annular relaxation velocity (e') assessed by echocardiography. Elastic modulus of living cardiomyocytes in the transverse direction assessed by an atomic force microscope was significantly higher in the ISO group than in controls. We added butanedione monoxime (BDM), an inhibitor of actin-myosin interaction, and blebbistatin, a specific myosin II inhibitor, to the medium. BDM and blebbistatin significantly reduced the elastic modulus of cardiomyocytes in the ISO group. X-ray diffraction analysis showed that the reflection intensity ratio (I((1,0))/I((1,1))) at diastole was not different before and after treatment with BDM, which induces complete relaxation, in control hearts, but that I((1,0))/I((1,1)) was significantly increased after BDM treatment in the ISO group, indicating residual cross-bridge formation in hypertrophied hearts. CONCLUSIONS: Passive cardiomyocyte stiffness in the transverse direction is increased in hearts with ISO-induced hypertrophy and this is caused by residual actin-myosin cross-bridge formation.

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  • The compound mutation, a model for acquire long QT syndrome.

    Hiroshi Morita

    Journal of cardiology cases   6 ( 6 )   e187-e188   2012.12

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  • PDGF-BB Activates Inflammatory Signaling in Pulmonary Arterial Smooth Muscle Cells from Patients with Idiopathic Pulmonary Arterial Hypertension Reviewed

    Kazufumi Nakamura, Satoshi Akagi, Hiromi Matsubara, Aiko Ogawa, Aya Miura, Daiji Miura, Toru Miyoshi, Satoshi Nagase, Hiroshi Morita, Kunihisa Kohno, Kengo F. Kusano, Hiroshi Ito

    CIRCULATION   126 ( 21 )   2012.11

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  • Cardiac dysfunction and prolonged hemodynamic deterioration after implantable cardioverter-defibrillator shock in patients with systolic heart failure. International journal

    Norihisa Toh, Nobuhiro Nishii, Kazufumi Nakamura, Takeshi Tada, Hiroki Oe, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Kengo F Kusano, Hiroshi Ito

    Circulation. Arrhythmia and electrophysiology   5 ( 5 )   898 - 905   2012.10

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    BACKGROUND: We investigated the acute effects of implantable cardioverter-defibrillator shock on myocardium, cardiac function, and hemodynamics in relation to left ventricular systolic function. METHODS AND RESULTS: We studied 50 patients who underwent implantable cardioverter-defibrillator implantation and defibrillation threshold (DFT) testing: 25 patients with left ventricular ejection fraction (LVEF) ≥ 45% and 25 patients with LVEF <45%. We measured cardiac biomarkers (creatine kinase, creatine kinase-MB, myoglobin, cardiac troponin T and I, and N-terminal probrain natriuretic peptide). Left ventricular relaxation was assessed by global longitudinal strain rate during the isovolumetric relaxation period using speckle-tracking echocardiography. Blood sampling and echocardiography were performed before, immediately after, and 5 minutes and 4 hours after DFT testing. Mean arterial pressure was measured directly during DFT testing. Cardiac biomarkers showed no significant changes in either group. LVEF was decreased until 5 minutes after DFT testing and had recovered to the baseline at 4 hours in the group with reduced LVEF (P<0.001), whereas LVEF reduction was not observed in the group with preserved LVEF (P=0.637). Global isovolumetric relaxation period was decreased until 5 minutes after DFT testing and had recovered to the baseline at 4 hours in both groups (preserved LVEF: 0.39 ± 0.14 versus 0.23 ± 0.13* versus 0.23 ± 0.13* versus 0.40 ± 0.13 s(-1), *P<0.001 versus baseline; reduced LVEF: 0.15 ± 0.05 versus 0.08 ± 0.04† versus 0.09 ± 0.04† versus 0.15 ± 0.05 s(-1), †P<0.001 versus baseline, repeated-measures ANOVA). Time to recovery of mean arterial pressure to the baseline was prolonged in the group with reduced LVEF (P<0.001). CONCLUSIONS: Implantable cardioverter-defibrillator shock transiently impairs cardiac function and hemodynamics especially in patients with systolic dysfunction, although significant tissue injury is not observed.

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  • 完全房室ブロックでペースメーカー植え込み後4年の経過を経て心サルコイドーシスと診断し得た一例

    内藤 優佳, 三好 章仁, 高谷 陽一, 永瀬 聡, 河野 晋久, 森田 宏, 草野 研吾, 伊藤 浩

    日本サルコイドーシス/肉芽腫性疾患学会雑誌   32 ( サプリメント号 )   43 - 43   2012.9

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  • Fragmented QRS: What Is The Meaning? International journal

    Yutaka Take, Hiroshi Morita

    Indian pacing and electrophysiology journal   12 ( 5 )   213 - 25   2012.9

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    Fragmented QRS (fQRS) is a convenient marker of myocardial scar evaluated by 12-lead electrocardiogram (ECG) recording. fQRS is defined as additional spikes within the QRS complex. In patients with CAD, fQRS was associated with myocardial scar detected by single photon emission tomography and was a predictor of cardiac events. fQRS was also a predictor of mortality and arrhythmic events in patients with reduced left ventricular function. The usefulness of fQRS for detecting myocardial scar and for identifying high-risk patients has been expanded to various cardiac diseases, such as cardiac sarcoidosis, arrhythmogenic right ventricular cardiomyopathy, acute coronary syndrome, Brugada syndrome, and acquired long QT syndrome. fQRS can be applied to patients with wide QRS complexes and is associated with myocardial scar and prognosis. Myocardial scar detected by fQRS is associated with subsequent ventricular dysfunction and heart failure and is a substrate for reentrant ventricular tachyarrhythmias.

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  • Pro-apoptotic effects of imatinib on PDGF-stimulated pulmonary artery smooth muscle cells from patients with idiopathic pulmonary arterial hypertension. International journal

    Kazufumi Nakamura, Satoshi Akagi, Aiko Ogawa, Kengo F Kusano, Hiromi Matsubara, Daiji Miura, Soichiro Fuke, Nobuhiro Nishii, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Takahiro Oto, Ryutaro Yamanaka, Fumio Otsuka, Aya Miura, Chikao Yutani, Tohru Ohe, Hiroshi Ito

    International journal of cardiology   159 ( 2 )   100 - 6   2012.8

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    BACKGROUND: Remodeling of the pulmonary artery by an inappropriate increase of pulmonary artery smooth muscle cells (PASMCs) is problematic in the treatment of idiopathic pulmonary arterial hypertension (IPAH). Effective treatment that achieves reverse remodeling is required. The aim of this study was to assess the pro-apoptotic effects of imatinib, a platelet-derived growth factor (PDGF)-receptor tyrosine kinase inhibitor, on PASMCs obtained from patients with IPAH. METHODS: PASMCs were obtained from 8 patients with IPAH undergoing lung transplantation. Cellular proliferation was assessed by (3)H-thymidine incorporation. Pro-apoptotic effects of imatinib were examined using TUNEL and caspase-3,7 assays and using transmission electron microscopy. RESULTS: Treatment with imatinib (0.1 to 10 μg/mL) significantly inhibited PDGF-BB (10 ng/mL)-induced proliferation of PASMCs from IPAH patients. Imatinib (1 μg/mL) did not induce apoptosis in quiescent IPAH-PASMCs, but it had a pro-apoptotic effect on IPAH-PASMCs stimulated with PDGF-BB. Imatinib did not induce apoptosis in normal control PASMCs with or without PDGF-BB stimulation. PDGF-BB induced phosphorylation of Akt at 15 min, and Akt phosphorylation was inhibited by imatinib in IPAH-PASMCs. Akt-I-1/2 (1 μmol/L), an Akt inhibitor, in the presence of PDGF-BB significantly increased apoptotic cells compared with the control condition. Thus, Akt-I-1/2 could mimic the effects of imatinib on PASMCs. CONCLUSION: Imatinib has anti-proliferative and pro-apoptotic effects on IPAH-PASMCs stimulated with PDGF. The inhibitory effect of imatinib on Akt phosphorylation induced by PDGF plays an important role in the pro-apoptotic effect.

    DOI: 10.1016/j.ijcard.2011.02.024

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  • Identification of high-risk syncope related to ventricular fibrillation in patients with Brugada syndrome. International journal

    Yutaka Take, Hiroshi Morita, Norihisa Toh, Nobuhiro Nishii, Satoshi Nagase, Kazufumi Nakamura, Kengo F Kusano, Tohru Ohe, Hiroshi Ito

    Heart rhythm   9 ( 5 )   752 - 9   2012.5

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    BACKGROUND: Syncope in patients with Brugada syndrome is usually associated with ventricular tachyarrhythmia, but some episodes of syncope can be related to autonomic disorders. OBJECTIVE: The purpose of this study was to investigate the characteristics of syncope to differentiate high-risk syncope episodes from low-risk events in patients with Brugada syndrome. METHODS: We studied 84 patients with type 1 electrocardiogram and syncope. Patients were divided into 2 groups: patients with prodrome (prodromal group; n = 41) and patients without prodrome (nonprodromal group; n = 43). RESULTS: Ventricular fibrillation (VF) was documented at index event in 19 patients: 4 patients (21%) with documented VF experienced a prodrome prior to the onset of VF, whereas 15 patients (79%) did not have symptoms prior to documented VF (P <.01). Twenty-seven patients in the prodromal group and 7 patients in the nonprodromal group were considered to have syncope related to autonomic dysfunction. Syncope in other patients was defined as unexplained syncope. During the follow-up period (48 ± 48 months), recurrent syncope due to VF occurred in 13 patients among patients with only unexplained syncope and was more frequent in the nonprodromal group (n = 10) than in the prodromal group (n = 3; P = .044). In multivariate analysis, blurred vision (hazard ratio [HR] 0.20) and abnormal respiration (HR 2.18) and fragmented QRS (HR 2.39) were independently associated with the occurrence of VF. CONCLUSION: Syncope with prodrome, especially blurred vision, suggests a benign etiology of syncope in patients with Brugada syndrome.

    DOI: 10.1016/j.hrthm.2011.11.045

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  • Acute vasoreactivity testing with nicardipine in patients with pulmonary arterial hypertension.

    Yukihiro Saito, Kazufumi Nakamura, Katsumasa Miyaji, Satoshi Akagi, Hiroki Mizoguchi, Aiko Ogawa, Soichiro Fuke, Hideki Fujio, Takahiko Kiyooka, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Kengo F Kusano, Hiromi Matsubara, Tohru Ohe, Hiroshi Ito

    Journal of pharmacological sciences   120 ( 3 )   206 - 12   2012

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    Acute vasoreactivity testing for patients with pulmonary arterial hypertension (PAH) has been reported to be useful to identify patients with sustained beneficial response to oral calcium-channel blockers (CCBs), but there is a risk of exacerbation during the testing with oral CCBs. Therefore, we developed a testing method utilizing intravenous nicardipine, a short-acting CCB, and examined the safety and usefulness of acute vasoreactivity testing with nicardipine in PAH patients. Acute vasoreactivity testing with nicardipine was performed in 65 PAH patients. Nicardipine was administered by short-time continuous infusion (1 μg·kg⁻¹·min⁻¹ for 5 min and 2 μg·kg⁻¹·min⁻¹ for 5 min) followed by bolus injection (5 μg/kg). Hemodynamic responses were continuously measured using a right heart catheter. Acute responders were defined as patients who showed a decrease in mean pulmonary artery pressure of at least 10 mmHg to an absolute level below 40 mmHg with preserved or increased cardiac output. Two acute responders and sixty-three non-acute responders were identified. There was no hemodynamic instability requiring additional inotropic agents or death during the testing. Acute responders had good responses to long-term oral CCBs. The acute vasoreactivity testing with nicardipine might be safe and useful for identifying CCB responders in PAH patients.

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  • Sustained monomorphic ventricular tachycardia in patients with Brugada syndrome

    Take Yutaka, Morita Hiroshi, Toh Norihisa, Nishii Nobuhiro, Hashimoto Katsushi, Nagase Satoshi, Nakamura Kazuhumi, Kohno Kunihisa, Kusano Kengo, Ohe Tohru, Ito Hiroshi

    Shinzo   44 ( 2 )   S2_55 - S2_55   2012

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    DOI: 10.11281/shinzo.44.S2_55

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  • J Wave in Brugada Syndrome -- Comparison to Early Repolarization Syndrome --

    Shimizu Wataru, Kawata Hiro, Morita Hiroshi, Ito Hiroshi, Kamakura Shiro

    Japanese Journal of Electrocardiology   32 ( 3 )   300 - 304   2012

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    DOI: 10.5105/jse.32.300

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    Other Link: http://search.jamas.or.jp/link/ui/2013010092

  • Intermittent arm ischemia induces vasodilatation of the contralateral upper limb.

    Kenki Enko, Kazufumi Nakamura, Kei Yunoki, Toru Miyoshi, Satoshi Akagi, Masashi Yoshida, Norihisa Toh, Mutsuko Sangawa, Nobuhiro Nishii, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Kengo F Kusano, Hiroshi Ito

    The journal of physiological sciences : JPS   61 ( 6 )   507 - 13   2011.11

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    Intermittent arm ischemia before percutaneous coronary intervention induces remote ischemic preconditioning (RIPC) and attenuates myocardial injury in patients with myocardial infarction. Several studies have shown that intermittent arm ischemia increases coronary flow and is related to autonomic nerve system. The aim of this study was to determine whether intermittent arm ischemia induces vasodilatation of other arteries and to assess changes in the autonomic nerve system during intermittent arm ischemia in humans. We measured change in the right brachial artery diameter during intermittent left arm ischemia through three cycles of 5-min inflation (200 mmHg) and 5-min deflation of a blood-pressure cuff using a 10-MHz linear array transducer probe in 20 healthy volunteers. We simultaneously performed power spectral analysis of heart rate. Ischemia-reperfusion of the left arm significantly dilated the right brachial artery time-dependently, resulting in a 3.2 ± 0.4% increase after the 3rd cycle. In the power spectral analysis of heart rate, the high-frequency domain (HF), which is a marker of parasympathetic activity, was significantly higher after the 3rd cycle of ischemia-reperfusion than baseline HF (P = 0.02). Intermittent arm ischemia was accompanied by vasodilatation of another artery and enhancement of parasympathetic activity. Those effects may play an important role in the mechanism of RIPC.

    DOI: 10.1007/s12576-011-0172-9

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  • Beta-Blockers and Oxidative Stress in Patients with Heart Failure. International journal

    Kazufumi Nakamura, Masato Murakami, Daiji Miura, Kei Yunoki, Kenki Enko, Masamichi Tanaka, Yukihiro Saito, Nobuhiro Nishii, Toru Miyoshi, Masashi Yoshida, Hiroki Oe, Norihisa Toh, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Hiromi Matsubara, Kengo F Kusano, Tohru Ohe, Hiroshi Ito

    Pharmaceuticals (Basel, Switzerland)   4 ( 8 )   1088 - 100   2011.8

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    Oxidative stress has been implicated in the pathogenesis of heart failure. Reactive oxygen species (ROS) are produced in the failing myocardium, and ROS cause hypertrophy, apoptosis/cell death and intracellular Ca(2+) overload in cardiac myocytes. ROS also cause damage to lipid cell membranes in the process of lipid peroxidation. In this process, several aldehydes, including 4-hydroxy-2-nonenal (HNE), are generated and the amount of HNE is increased in the human failing myocardium. HNE exacerbates the formation of ROS, especially H₂O₂ and ·OH, in cardiomyocytes and subsequently ROS cause intracellular Ca(2+) overload. Treatment with beta-blockers such as metoprolol, carvedilol and bisoprolol reduces the levels of oxidative stress, together with amelioration of heart failure. This reduction could be caused by several possible mechanisms. First, the beta-blocking effect is important, because catecholamines such as isoproterenol and norepinephrine induce oxidative stress in the myocardium. Second, anti-ischemic effects and negative chronotropic effects are also important. Furthermore, direct antioxidative effects of carvedilol contribute to the reduction of oxidative stress. Carvedilol inhibited HNE-induced intracellular Ca(2+) overload. Beta-blocker therapy is a useful antioxidative therapy in patients with heart failure.

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  • Ezetimibe improves postprandial hyperlipemia and its induced endothelial dysfunction Reviewed

    Kei Yunoki, Kazufumi Nakamura, Toru Miyoshi, Kenki Enko, Kunihisa Kohno, Hiroshi Morita, Kengo F. Kusano, Hiroshi Ito

    ATHEROSCLEROSIS   217 ( 2 )   486 - 491   2011.8

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    Objective: Postprandial hyperlipemia has been shown to impair endothelial function and contribute to the development of atherosclerosis. We investigated the association between postprandial lipid profiles and endothelial function, and we examined the effects of ezetimibe on postprandial hyperlipemia and lipemia-induced endothelial dysfunction.
    Methods: A randomized prospective trial in which 10 mg/day of ezetimibe was administered to 10 subjects for 4 weeks and not administered to 10 subjects (control group) was performed. Lipid profiles and endothelial function, assessed by brachial artery flow-mediated dilation (FMD) during a fasting state and at 2, 4, 6 and 8 h after an oral cookie loading test, were determined before and after treatment for 4 weeks.
    Results: In all subjects before treatment, the maximum reduction in postprandial % FMD was significantly correlated with the maximum increases in postprandial triglyceride (TG) (r = -0.499, P &lt; 0.05) and apolipoprotein B-48 (apoB-48) concentrations (r = -0.551, P &lt; 0.05). Ezetimibe treatment for 4 weeks significantly suppressed postprandial elevation in TG (area under the incremental curve, from 1419 +/- 594 to 968 +/- 321 mg h/dl, P &lt; 0.05), remnant lipoprotein cholesterol (from 66.9 +/- 27.6 to 38.9 +/- 15.4 mg h/dl, P &lt; 0.01) and apoB-48 (from 58.8 +/- 27.5 to 36.2 +/- 17.0 mu gh/ml, P &lt; 0.05) concentrations, and postprandial endothelial dysfunction assessed by % FMD (maximum reduction in % FMD, from -2.6 +/- 1.1% to -1.2 +/- 0.8%, P &lt; 0.05), whereas no significant changes were observed in the control group.
    Conclusion: Postprandial hyperlipemia is closely correlated with transient endothelial dysfunction. Ezetimibe improves postprandial hyperlipemia and its induced endothelial dysfunction. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

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  • Impact of Hypertriglyceridemia on Endothelial Dysfunction During Statin +/- Ezetimibe Therapy in Patients With Coronary Heart Disease Reviewed

    Kei Yunoki, Kazufumi Nakamura, Toru Miyoshi, Kenki Enko, Motoki Kubo, Masato Murakami, Yoshiki Hata, Kunihisa Kohno, Hiroshi Morita, Kengo F. Kusano, Hiroshi Ito

    AMERICAN JOURNAL OF CARDIOLOGY   108 ( 3 )   333 - 339   2011.8

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    Despite the use of statin therapy and achieving the target for low-density lipoprotein cholesterol, a substantial number of coronary events are not prevented, and residual risk factors remain unsettled. Recently, ezetimibe has been shown to reduce not only low-density lipoprotein cholesterol but also triglyceride (TG) levels. The aim of this study was to investigate the associations of residual risk factors, mainly hypertriglyceridemia, with endothelial function during statin therapy in patients with coronary heart disease and examine the effect of ezetimibe add-on therapy. A total of 109 consecutive patients with coronary heart disease during statin therapy were enrolled. Lipid profile was measured and endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery in a fasting state. Next, 32 patients with high TG levels (&gt;= 150 mg/dl) were prospectively assigned to the ezetimibe add-on group or the no-ezetimibe group, and endothelial function was assessed after 3 months. Multivariate linear regression analysis demonstrated that serum TG and high-density lipoprotein cholesterol levels were independent determinants of percentage FMD (beta = -0.210 and 0.208, respectively, p &lt;0.05). In patients with high TG levels, ezetimibe add-on therapy significantly improved percentage FMD (from 3.3 +/- 1.1% to 4.0 +/- 1.1%, p &lt;0.005), whereas no significant change was observed in the no-ezetimibe group. Moreover, the improvement in percentage FMD was significantly associated with reduction in serum TG levels (beta = -0.387, p &lt;0.05) independent of the change in serum low-density lipoprotein cholesterol levels. In conclusion, hypertriglyceridemia is independently associated with endothelial dysfunction in patients with coronary heart disease during statin therapy. Ezetimibe add-on therapy improves endothelial function in these high-risk populations. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:333-339)

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  • How can we stabilize QT variability? International journal

    Hiroshi Morita

    Heart rhythm   8 ( 8 )   1243 - 4   2011.8

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  • Spontaneous electrocardiogram alterations predict ventricular fibrillation in Brugada syndrome. International journal

    Yutaka Take, Hiroshi Morita, Jiashin Wu, Satoshi Nagase, Shiho Morita, Norihisa Toh, Nobuhiro Nishii, Kazufumi Nakamura, Kengo F Kusano, Tohru Ohe, Hiroshi Ito, Douglas P Zipes

    Heart rhythm   8 ( 7 )   1014 - 21   2011.7

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    BACKGROUND: Patients with Brugada syndrome (BS) often have spontaneous changes in their electrocardiogram (ECG). OBJECTIVE: To evaluate the significance of ECG alterations, we investigated the relationships between the ECG and the occurrence of ventricular fibrillation (VF) in both patients and an experimental model of BS. METHODS: In study 1, we evaluated ECG alterations in BS patients with (VF+, n = 33) and without (VF-, n = 41) spontaneous VF. We defined type 0 ECG as coved-type ST elevation without a negative T wave, which represents the existence of loss-of-dome (LOD) type action potentials (APs). In study 2, we optically mapped epicardial APs and recorded transmural ECGs in 34 canine right ventricular tissues with a drug-induced BS model by a combination of pinacidil and pilsicainide. RESULTS: In study 1, changes in ST level ≥0.2 mV were more frequent in the VF+ group than in the VF- group (P <.01). Spontaneous ECG alterations and appearances of types 1 and 0 ECGs were more frequent in the VF+ group than in the VF- group (P <.01). In study 2, BS model with spike-and-dome (SAD) epicardial APs exhibited type 1 ECG. Deepening of the phase 1 notch of the APs induced heterogeneous conversion of the APs (SAD→LOD) and resulted in ECG conversion from type 1 to type 0. Significant AP heterogeneity often appeared during AP alterations and initiated phase 2 reentry. Tissues having ventricular tachycardia (VT; n = 20) had more frequent alterations in APs and ECG than in tissues without VT (n = 14; P <.01). CONCLUSION: ECG alterations, especially conversion between types 0 and 1, are associated with significant AP heterogeneity that can initiate VF in BS.

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  • IMPACT OF INCREASED ARTERIAL STIFFNESS AND WAVE REFLECTION ON THE PREVALENCE OF PAROXYSMAL ATRIAL FIBRILLATION

    Toru Miyoshi, Msayuki Doi, Satoshi Hirohata, Shozo Kusachi, Kazufumi Nakamura, Satoshi Nagase, Kunihisa Kono, Hiroshi Morita, Kengo Kusano, Hiroshi Ito

    JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY   57 ( 14 )   E563 - E563   2011.4

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  • Indication of implantable cardioverter defibrillator for myotonic dystrophy in patients with high degree atrio-ventricular block

    Take Yutaka, Morita Hiroshi, Nishii Nobuhiro, Nagase Satoshi, Nakamura Kazuhumi, Kohno Kunihisa, Kusano Kengo, Ito Hiroshi

    Shinzo   43 ( 2 )   S2_39 - S2_45   2011

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  • Significance of Delayed Gadolinium Enhancement Cardiac Magnetic Resonance in Patients with Brugada Syndrome

    Murakami Masato, Nagase Satoshi, Morita Hiroshi, Kusano Kengo, Suenaga Hidetaka, Ito Hiroshi, Saito Shigeru

    J Arrhythmia   27   OP36_2   2011

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    Introduction: Gadlinium-enhanced Cardiac magnetic resonance (CMR) is a useful diagnostic tool for evaluating myocardial abnormality. However, the prevalence of delyed Gadlinium enhancement (DGE) in CMR has not been yet reported in patients with Brugada syndrome (BrS). Methods and Results: Seventy consecutive patients with BrS who underwent Gadlinium-enhanced CMR were evaluated in this study. DGE was found in five patients (7.1%). All patients with DGE were symptomatic. Early repolarization (ER) in inferolateral leads was significantly highly detected in patients with DGE than without DGE (80.0% vs 16.9%, P<0.01). Late potentials examined with SAECG were present in all patients with DGE and in 42 of 65 patients without DGE (64.6%). The value of RMS40 evaluated with SAECG was significantly smaller in patients with DGE than in patients without DGE (p<0.0001). In electrophysiologic study, VF was induced with programmed ventricular stimulation in four of five patients with DGE (80.0%) and in 21 of 41 patients without DGE (51.2%). Mutation analysis revealed that DGE was present in one patient with SCN5A mutation and in 2 patients without SCN5A mutation. Conclusions: Depolarization abnormality is prominent in BrS patients with DGE. CMR with DGE might be a useful tool for evaluating high risk patient with BrS.

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  • Circulating KCNH2 current-activating factor in patients with heart failure and ventricular tachyarrhythmia. International journal

    Hiroki Sugiyama, Kazufumi Nakamura, Hiroshi Morita, Satoshi Akagi, Yoshinori Tani, Yusuke Katayama, Nobuhiro Nishii, Toru Miyoshi, Satoshi Nagase, Kunihisa Kohno, Kengo Fukushima Kusano, Tohru Ohe, Junko Kurokawa, Tetsushi Furukawa, Hiroshi Ito

    PloS one   6 ( 5 )   e19897   2011

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    BACKGROUND: It is estimated that approximately half of the deaths in patients with HF are sudden and that the most likely causes of sudden death are lethal ventricular tachyarrhythmias such as ventricular tachycardia (VT) or fibrillation (VF). However, the precise mechanism of ventricular tachyarrhythmias remains unknown. The KCNH2 channel conducting the delayed rectifier K(+) current (I(Kr)) is recognized as the most susceptible channel in acquired long QT syndrome. Recent findings have revealed that not only suppression but also enhancement of I(Kr) increase vulnerability to major arrhythmic events, as seen in short QT syndrome. Therefore, we investigated the existence of a circulating KCNH2 current-modifying factor in patients with HF. METHODOLOGY/PRINCIPAL FINDINGS: We examined the effects of serum of HF patients on recombinant I(Kr) recorded from HEK 293 cells stably expressing KCNH2 by using the whole-cell patch-clamp technique. Study subjects were 14 patients with non-ischemic HF and 6 normal controls. Seven patients had a history of documented ventricular tachyarrhythmias (VT: 7 and VF: 1). Overnight treatment with 2% serum obtained from HF patients with ventricular arrhythmia resulted in a significant enhancement in the peaks of I(Kr) tail currents compared to the serum from normal controls and HF patients without ventricular arrhythmia. CONCLUSIONS/SIGNIFICANCE: Here we provide the first evidence for the presence of a circulating KCNH2 channel activator in patients with HF and ventricular tachyarrhythmias. This factor may be responsible for arhythmogenesis in patients with HF.

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  • Electroanatomical correlation of repolarization abnormalities in Brugada syndrome: detection of type 1 electrocardiogram in the right ventricular outflow tract. International journal

    Satoshi Nagase, Shigeki Hiramatsu, Hiroshi Morita, Nobuhiro Nishii, Masato Murakami, Kazufumi Nakamura, Kengo F Kusano, Hiroshi Ito, Tohru Ohe

    Journal of the American College of Cardiology   56 ( 25 )   2143 - 5   2010.12

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  • Fragmented QRS is associated with torsades de pointes in patients with acquired long QT syndrome. International journal

    Kayo Haraoka, Hiroshi Morita, Yukihiro Saito, Norihisa Toh, Toru Miyoshi, Nobuhiro Nishii, Satoshi Nagase, Kazufumi Nakamura, Kunihisa Kohno, Kengo F Kusano, Kenji Kawaguchi, Tohru Ohe, Hiroshi Ito

    Heart rhythm   7 ( 12 )   1808 - 14   2010.12

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    BACKGROUND: Acquired long QT syndrome (LQTS) is a disease due to a secondary repolarization abnormality induced by various predisposing factors. In contrast to congenital LQTS, risk factors that produce acquired LQTS include organic heart diseases that often exhibit depolarization abnormality. Although various repolarization parameters have been evaluated in acquired LQTS, the existence of depolarization abnormality in association with torsades de pointes (TdP) has not been reported. OBJECTIVE: The purpose of this study was to evaluate both repolarization (QT components) and depolarization parameters (fragmented QRS [fQRS]) in acquired LQTS patients with markedly prolonged QT interval. METHODS: Seventy patients with acquired severe QT prolongation (QTc ≥ 550 ms) were studied. Thirty-two patients had syncope or TdP (syncope group). Thirty-eight patients did not have any symptoms (asymptomatic group). The existence of fQRS and QT components (QT, QTc, Tpe [interval between peak and end of T wave] intervals, and U-wave voltage) was analyzed. RESULTS: The syncope group had more frequent fQRS (81%) than did the asymptomatic group (21%, P < .01) and the incidence of fQRS was not different before and after removal of predisposing factors. The incidence of organic heart disease was not different between the two groups. No differences in QTc interval were noted between the syncope and asymptomatic groups, although the syncope group had longer QT and Tpe intervals and higher U wave than the asymptomatic group (P < .01). CONCLUSION: Acquired predisposing factors promoted repolarization abnormality (especially prolongation of QT and Tpe intervals), and the existence of fQRS had an important role in the development of TdP in patients with acquired LQTS.

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  • Anti-tachycardia pacing degenerated fast ventricular tachycardia into undetectable life-threatening tachyarrhythmia in a patient with non-ischemic dilated cardiomyopathy.

    Kei Yunoki, Nobuhiro Nishii, Hiroshi Morita, Jun Iwasaki, Satoshi Nagase, Kazufumi Nakamura, Yoshiki Hata, Kunihisa Kohno, Kengo F Kusano, Hiroshi Ito

    Journal of cardiology cases   2 ( 3 )   e159-e162   2010.12

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    A 45-year-old man with dilated cardiomyopathy was admitted to our hospital due to congestive heart failure (CHF). Despite the optimal medical treatment, his condition had not improved because of severe left ventricular dysfunction. Because he experienced non-sustained ventricular tachycardia (VT), a biventricular implantable cardioverter-defibrillator (Bi-V ICD) was implanted for reduction of dyssynchrony and primary prevention of lethal tachyarrhythmia. After discharge, he developed CHF and was transported to our hospital by ambulance. In the ambulance, monomorphic sustained VT with 200 bpm suddenly occurred. The ICD detected it as fast VT and anti-tachycardia pacing (ATP) was delivered. After the ATP therapy, RR intervals of VT became irregular and prolonged. Ventricular fibrillation-like electrical activity was recorded by a far-field electrogram from the defibrillator, but the tachycardia cycle length exceeded 400 ms which is under the tachycardia detection rate. The device failed to deliver a shock and the patient had to be rescued with an external shock. This is a rare case of fast VT that degenerated into undetectable life-threatening tachyarrhythmia by ATP.

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  • SCN5A mutation is associated with early and frequent recurrence of ventricular fibrillation in patients with Brugada syndrome.

    Nobuhiro Nishii, Masahiro Ogawa, Hiroshi Morita, Kazufumi Nakamura, Kimikazu Banba, Daiji Miura, Naoko Kumagai, Akira Matsunaga, Hiroshi Kawamura, Shigemi Urakawa, Kohei Miyaji, Masahiro Nagai, Katsumasa Satoh, Koji Nakagawa, Masamichi Tanaka, Shigeki Hiramatsu, Takeshi Tada, Masato Murakami, Satoshi Nagase, Kunihisa Kohno, Kengo Fukushima Kusano, Keijiro Saku, Tohru Ohe, Hiroshi Ito

    Circulation journal : official journal of the Japanese Circulation Society   74 ( 12 )   2572 - 8   2010.11

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    BACKGROUND: Mutations in SCN5A are reportedly linked to Brugada syndrome (BS), but recent observations suggest that they are not necessarily associated with ventricular fibrillation (VF) in BS patients. Therefore, the clinical importance of SCN5A mutations in BS patients was examined in the present study. METHODS AND RESULTS:  The 108 BS patients were examined for SCN5A mutations and various parameters were compared between patients with and without mutations. An implantable cardioverter defibrillator (ICD) was implanted in 49 patients and a predictor of appropriate ICD shock was investigated. The existence of a SCN5A mutation was not associated with initial VF episodes (21.7% vs 20.0%, P=0.373). In the secondary prevention group, appropriate shock-free survival rate was significantly lower in patients with spontaneous type 1 ECG than in those without (41.1% vs 85.7% at 2 years, P=0.014). The appropriate shock-free survival rate was also significantly lower in patients with SCN5A mutations than in those without (28.6% vs 83.3% at 1 year, P=0.040). Appropriate shock was more frequent in patients with SCN5A mutations than in those without (6.6±6.2 vs 1.7±3.0, P=0.007). CONCLUSIONS: SCN5A mutations are associated with early and frequent VF recurrence, but not with initial VF episodes. This is the first report on the genotype-phenotype interaction and clinical significance of this mutation.

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  • Imatinib in the Presence of Platelet-derived Growth Factor Inhibits Proliferation and Induces Apoptosis in Pulmonary Artery Smooth Muscle Cells from Patients with Idiopathic Pulmonary Arterial Hypertension Reviewed

    Kazufumi Nakamura, Satoshi Akagi, Hiromi Matsubara, Aiko Ogawa, Aya Miura, Daiji Miura, Nobuhiro Nishii, Satoshi Nagase, Kunihisa Kohno, Hiroshi Morita, Kengo F. Kusano, Hiroshi Ito

    CIRCULATION   122 ( 21 )   2010.11

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  • Efficacy of low-dose bepridil for prevention of ventricular fibrillation in patients with Brugada syndrome with and without SCN5A mutation. International journal

    Masato Murakami, Kazufumi Nakamura, Kengo F Kusano, Hiroshi Morita, Koji Nakagawa, Masamichi Tanaka, Takeshi Tada, Norihisa Toh, Nobuhiro Nishii, Satoshi Nagase, Yoshiki Hata, Kunihisa Kohno, Daiji Miura, Tohru Ohe, Hiroshi Ito

    Journal of cardiovascular pharmacology   56 ( 4 )   389 - 95   2010.10

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    It has been reported that bepridil prevents ventricular fibrillation (VF) in patients with Brugada syndrome, but the comparative efficacy with and without mutation in the SCN5A gene has not been elucidated. The purpose of this study was to assess the efficacy of low-dose bepridil (100 mg/day) for VF prevention in patients with Brugada syndrome with and without SCN5A mutation. Among 130 patients with Brugada-type electrocardiogram (ECG), low-dose bepridil was administered to seven patients because of repetitive VF episodes, including three with and four without SCN5A mutation. Preventive effect for VF recurrence and changes of the ECG and the signal-averaged ECG were evaluated. Frequencies of VF episodes were reduced after treatment with low-dose bepridil in all three patients with the SCN5A mutation (before: 0.33 versus after: 0.02 episodes/month, P < 0.01), but not in all four patients without the SCN5A mutation (before: 0.43 versus after: 2.94 episodes/month, P = nonsignificant). Levels of ST-segment elevation at J points and duration of low-amplitude signals less than 40 µV in the terminal filtered QRS complex (LAS40) in signal-averaged ECG were improved exclusively in patients with the SCN5A mutation. Treatment with bepridil prevented recurrence of VF along with improvement of ST elevation and LAS40 in patients with Brugada syndrome with the SCN5A mutation.

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  • The pathophysiological mechanism underlying Brugada syndrome: depolarization versus repolarization. International journal

    Arthur A M Wilde, Pieter G Postema, José M Di Diego, Sami Viskin, Hiroshi Morita, Jeffrey M Fish, Charles Antzelevitch

    Journal of molecular and cellular cardiology   49 ( 4 )   543 - 53   2010.10

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    This Point/Counterpoint presents a scholarly debate of the mechanisms underlying the electrocardiographic and arrhythmic manifestations of Brugada syndrome (BrS), exploring in detail the available evidence in support of the repolarization vs. depolarization hypothesis.

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  • Brugada症候群における酸化ストレスと心室細動発症の関連

    田中 正道, 中村 一文, 大郷 恵子, 三浦 大志, 三浦 綾, 西井 伸洋, 永瀬 聡, 幡 芳樹, 森田 宏, 草野 研吾, 大江 透, 伊藤 浩, 由谷 親夫

    心臓   42 ( 10 )   1369 - 1369   2010.10

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  • 免疫と不整脈 K+チャネル自己抗体による後天性QT延長症候群 自己免疫性QT延長症候群

    中村 一文, 杉山 洋樹, 三浦 大志, 森田 宏, 草野 研吾, 伊藤 浩, 片山 祐介, 大江 透

    心電図   30 ( Suppl.3 )   S - 28   2010.7

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  • Genotype-phenotype correlation in tissue models of Brugada syndrome simulating patients with sodium and calcium channelopathies. International journal

    Hiroshi Morita, Douglas P Zipes, Shiho T Morita, Jiashin Wu

    Heart rhythm   7 ( 6 )   820 - 7   2010.6

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    BACKGROUND: Genetic defects in the sodium channel or in the calcium channel have been identified in patients with Brugada syndrome (BS). However, the differences in their genotype-phenotype correlations are still unclear. OBJECTIVE: We evaluated the phenotypic differences and therapeutic effects between the sodium channel and calcium channel abnormalities in in vitro models of BS. METHODS: We created two models of BS in 18 isolated and arterially perfused canine right ventricular preparations: (1) sodium channel dysfunction model (Na model, n = 11) by pilsicainide and pinacidil and (2) calcium channel dysfunction model (Ca model, n = 7) by verapamil; optically mapped action potentials (APs) on their transmural surface; and evaluated APs and electrocardiograms (ECGs) at pacing cycle lengths (CLs) of 2,000 and 1,000 ms. RESULTS: CL = 1,000 ms: Both models had coved-type ST elevation in the ECG, longer AP duration (APD) in the epicardium than in the endocardium, and a similar incidence of spontaneous ventricular arrhythmias. However, the Ca model had a higher incidence of T wave alternans (TWA) than the Na-model. CL = 2,000 ms: ECGs of the Ca model converted to saddleback-type ST elevation with shorter APDs in the epicardium than in the endocardium, whereas the Na model still had coved-type ST elevation and longer APDs in the epicardium. None of the Ca model preparations had ventricular arrhythmias or TWA, although the Na model had frequent ventricular arrhythmias and TWA. CONCLUSION: Although both sodium channel and calcium channel dysfunction produced similar BS ECGs and arrhythmogenesis at 60 bpm, calcium channel dysfunction was associated with a higher incidence of TWA at 60 bpm, less ST elevation, and fewer arrhythmias at 30 bpm compared with sodium channel dysfunction.

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  • Abnormal restitution property of action potential duration and conduction delay in Brugada syndrome: both repolarization and depolarization abnormalities. International journal

    Nobuhiro Nishii, Satoshi Nagase, Hiroshi Morita, Kengo Fukushima Kusano, Tsunetoyo Namba, Daiji Miura, Kohei Miyaji, Shigeki Hiramatsu, Takeshi Tada, Masato Murakami, Atsuyuki Watanabe, Kimikazu Banba, Yoshiaki Sakai, Kazufumi Nakamura, Takefumi Oka, Tohru Ohe

    Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology   12 ( 4 )   544 - 52   2010.4

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    AIMS: This study sought to examine the action potential duration restitution (APDR) property and conduction delay in Brugada syndrome (BrS) patients. A steeply sloped APDR curve and conduction delay are known to be important determinants for the occurrence of ventricular fibrillation (VF). METHODS AND RESULTS: Endocardial monophasic action potential was obtained from 39 BrS patients and 9 control subjects using the contact electrode method. Maximum slopes of the APDR curve were obtained at both the right ventricular outflow tract (RVOT) and the right ventricular apex (RVA). The onset of activation delay (OAD) after premature stimulation was examined as a marker of conduction delay. Maximum slope of the APDR curve in BrS patients was significantly steeper than that in control subjects at both the RVOT and the RVA (0.77 +/- 0.21 vs. 058 +/- 0.14 at RVOT, P = 0.009; 0.98 +/- 0.23 vs. 0.62 +/- 0.16 at RVA, P = 0.001). The dispersion of maximum slope of the APDR curve between the RVOT and the RVA was also larger in BrS patients than in control subjects. The OAD was significantly longer in BrS patients than in control subjects from the RVOT to RVA and from the RVA to RVOT (from RVOT to RVA: 256 +/- 12 vs. 243 +/- 7 ms, P = 0.003; from RVA to RVOT: 252 +/- 11 vs. 241 +/- 9 ms, P = 0.01). CONCLUSIONS: Abnormal APDR properties and conduction delay were observed in BrS patients. Both repolarization and depolarization abnormalities are thought to be related to the development of VF in BrS patients.

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  • A case with asymptomatic fatal event which could be early detected by remote monitoring system

    Nishii Nobuhiro, Nagase Satoshi, Nakamura Kazufumi, Hata Yoshiki, Kawano Akihisa, Morita Hiroshi, Kusano Kengo, Ito Hiroshi

    Shinzo   42 ( 2 )   S2_147 - S2_151   2010

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    DOI: 10.11281/shinzo.42.S2_147

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  • Arrhythmias in Cardiac Sarcoidosis

    Kusano Kengo, Banba Kimikazu, Takaya Yoichi, Nishii Nobuhiro, Nagase Satoshi, Nakamura Kazufumi, Morita Hiroshi, Ito Hiroshi, Ohe Tohru

    SARUKOIDOJISU KENKYUKAIZASSHI (The Japanese journal of sarcoidosis)   30 ( 1 )   83 - 85   2010

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    DOI: 10.7878/jjsogd.30.83

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  • Atrial electrophysiological and structural remodeling in high-risk patients with Brugada syndrome: assessment with electrophysiology and echocardiography. International journal

    Norihisa Toh, Hiroshi Morita, Satoshi Nagase, Manabu Taniguchi, Daiji Miura, Nobuhiro Nishii, Kazufumi Nakamura, Tohru Ohe, Kengo F Kusano, Hiroshi Ito

    Heart rhythm   7 ( 2 )   218 - 24   2010

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    BACKGROUND: Atrial fibrillation (AF) often occurs in Brugada syndrome (BrS), and BrS patients with spontaneous AF often experience ventricular fibrillation (VF) attacks. Atrial vulnerability providing a substrate for AF is known to be enhanced in BrS, but there are no data on atrial structural attributes. OBJECTIVE: The objective of this study was to assess atrial electrophysiological and structural characteristics in BrS and their relationships with gene mutations. METHODS: We studied 57 patients with BrS. Intra-atrial conduction time (CT) was defined as the interval from the stimulus at the high right atrium to atrial deflection at the distal portion of the coronary sinus. Left atrial volume index (LAVI) was measured by the modified Simpson method at left ventricular end-systole using echocardiography. SCN5A mutations were analyzed in all patients. RESULTS: In patients with documented VF, spontaneous AF frequently occurred and prolonged CT and increased LAVI were observed compared with those in patients without VF (all P < .05; LAVI: 22 +/- 5 vs. 32 +/- 7 ml/m(2)). Even among patients without AF, CT and LAVI were still increased in patients with VF (all P < .05; LAVI: 22 +/- 5 vs. 29 +/- 5 ml/m(2)). The presence of SCN5A mutation was associated with prolonged CT (P < .05) and increased LAVI (P < .01), but not with arrhythmic episodes. CONCLUSION: Both atrial vulnerability and structural remodeling are enhanced in high-risk patients with BrS, even in those without AF. These morphological characteristics suggest that BrS is a form of genetic myocardial disease.

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  • Cytokine reducing effect of azelnidipine in human peripheral blood mononuclear cells.

    Ryuzea Miura, Kazufumi Nakamura, Daiji Miura, Aya Miura, Masahito Kajiya, Kenichi Hisamatsu, Satoshi Nagase, Hiroshi Morita, Kengo Fukushima Kusano, Hiromi Matsubara, Tohru Ohe, Hiroshi Ito

    Biological & pharmaceutical bulletin   33 ( 7 )   1148 - 51   2010

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    Numerous clinical trials have shown that calcium channel blocker (CCB) therapy improves the clinical outcome in patients with cardiovascular diseases. Since the progression of several types of cardiovascular diseases is closely associated with inflammation, alleviation of inflammation may be one potential mechanism of those beneficial effects of CCB therapy. We examined whether a new CCB (azelnidipine) could influence the inflammatory response of human peripheral blood mononuclear cells (PBMCs), which are recruited to inflammatory lesions and modulate inflammation. We investigated whether azelnidipine affected intracellular signaling and cytokine production by phytohemagglutinin (PHA)-stimulated human PBMCs in vitro. PBMCs were obtained from 10 healthy volunteers and stimulated with PHA. Then relative intracellular calcium ion concentration ([Ca(2+)](i)) was assessed by fluorescence microscopy, and the production of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assay. Stimulation with PHA significantly raised [Ca(2+)](i) and enhanced the production of MCP-1 and TNF-alpha by human PBMCs. Azelnidipine significantly diminished the PHA-induced rise of [Ca(2+)](i), and the production of MCP-1 and TNF-alpha. These findings indicate that azelnidipine might have an anti-inflammatory influence on human PBMCs, although the mechanisms and the difference from other CCBs still remain unclear and further exploration should be required.

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  • Brugada syndrome: insights of ST elevation, arrhythmogenicity, and risk stratification from experimental observations. International journal

    Hiroshi Morita, Douglas P Zipes, Jiashin Wu

    Heart rhythm   6 ( 11 Suppl )   S34-43   2009.11

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    Brugada syndrome (BrS), caused by ion channel abnormalities, is characterized by ST segment elevation and negative T waves in the right precordial electrocardiographic (ECG) leads recorded over the right ventricular outflow tract (RVOT). BrS is sensitive to body temperature and can lead to T-wave alternans (TWA), ventricular tachycardia, and sudden death. Recent studies in an isolated canine RVOT model of BrS demonstrated that reversal of the transmural gradient of repolarization caused the ECG characteristics and that major intraepicardial and transmural dispersion of action potentials (APs) initiated phase 2 reentry, premature ventricular activations, and tachyarrhythmias. Hypothermia enhanced the heterogeneity of the AP and promoted the origination of phase 2 reentry in the epicardium of the RVOT, but the prolonged AP duration frequently blocked reentry. Hyperthermia abbreviated the AP and facilitated the maintenance of reentry and tachyarrhythmias. Bradycardia promoted alternans in the phase 2 dome of the AP within the epicardium of the RVOT, resulting in TWA. The above phenomena were localized in the epicardium of the RVOT. Blockade of the transient outward current, I(to), reduced AP heterogeneity and prevented arrhythmias in the BrS model. In addition, epicardial activation delay led to fragmented QRS, a risk marker of prognosis in BrS. Body surface mapping in patients with BrS supported these experimental findings. In conclusion, the AP heterogeneity within the epicardium of the RVOT contributes to the ECG characteristics, temperature sensitivity, TWA, and arrhythmias in BrS, and body surface mapping and fragmented QRS can be effective predictors of risk in patients with BrS.

    DOI: 10.1016/j.hrthm.2009.07.018

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  • Imatinib Inhibits Proliferation and Migration and Induces Apoptosis in Pulmonary Artery Smooth Muscle Cells From Patients With Idiopathic Pulmonary Arterial Hypertension Reviewed

    Kazufumi Nakamura, Satoshi Akagi, Hiromi Matsubara, Aiko Ogawa, Aya Miura, Daiji Miura, Nobuhiro Nishii, Satoshi Nagase, Hiroshi Morita, Yoshiki Hata, Kengo F. Kusano, Hiroshi Ito

    CIRCULATION   120 ( 18 )   S1136 - S1136   2009.11

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  • 4-Hydroxy-2-nonenal induces calcium overload via the generation of reactive oxygen species in isolated rat cardiac myocytes. International journal

    Kazufumi Nakamura, Daiji Miura, Kengo Fukushima Kusano, Yoshihisa Fujimoto, Wakako Sumita-Yoshikawa, Soichiro Fuke, Nobuhiro Nishii, Satoshi Nagase, Yoshiki Hata, Hiroshi Morita, Hiromi Matsubara, Tohru Ohe, Hiroshi Ito

    Journal of cardiac failure   15 ( 8 )   709 - 16   2009.10

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    BACKGROUND: It has been reported that that the amount of 4-hydroxy-2-nonenal (HNE), which is a major lipid peroxidation product and a cytotoxic aldehyde, is increased in the human failing myocardium. This study was designed to determine whether HNE has a pro-oxidant effect in cardiac myocytes and whether HNE causes Ca(2+) overload. METHODS AND RESULTS: Exposure to HNE for 10 minutes in the presence of ferric nitrilotriacetate induced the production of hydroxyl radical (.OH) in the rat myocardium as assessed by electron spin resonance spectroscopy, and HNE induced the generation of reactive oxygen species (ROS) in a dose-dependent manner as assessed by 2', 7'-dichlorofluorescein diacetate fluorescence. HNE increased intracellular Ca(2+) concentration ([Ca(2+)](i)) as assessed by fura-2 ratio in a dose- and time-dependent manner. After 20 minutes of HNE (400 micromol/L) exposure, hypercontracture was induced in 67% of the cells. Catalase, an antioxidative enzyme that can decompose hydrogen peroxide (H(2)O(2)), significantly attenuated the increase in [Ca(2+)](i) and completely inhibited hypercontracture. Carvedilol, a beta-blocker with potent antioxidant activity, also significantly attenuated the increase in [Ca(2+)](i) and completely inhibited hypercontracture, but propranolol had no effect on either [Ca(2+)](i) increase or hypercontracture. CONCLUSIONS: HNE induces the formation of ROS, especially H(2)O(2) and .OH, in cardiomyocytes and subsequently ROS cause intracellular Ca(2+) overload. HNE formation may play an important role as a mediator of oxidative stress in heart failure.

    DOI: 10.1016/j.cardfail.2009.04.008

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  • Abnormal transmural repolarization process in patients with Brugada syndrome. International journal

    Mutsuko Sangawa, Hiroshi Morita, Takaaki Nakatsu, Nobuhiro Nishii, Daiji Miura, Aya Miura, Takeshi Tada, Masato Murakami, Shigeki Hiramatsu, Satoshi Nagase, Kazufumi Nakamura, Takefumi Oka, Shinji Toyonaga, Keiichi Mashima, Shozo Kusachi, Kazuhide Yamamoto, Tohru Ohe, Kengo F Kusano

    Heart rhythm   6 ( 8 )   1163 - 9   2009.8

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    BACKGROUND: Repolarization abnormality, especially during bradycardia, might be critical for initiation of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS), but the contribution of the rate-dependent repolarization dynamics to the occurrence of VF is still unknown. OBJECTIVE: The aim of our study was to determine the differences in rate-dependent repolarization dynamics between BrS with and without spontaneous VF and between BrS with and without SCN5A mutation. METHODS: The subjects were 37 BrS patients with VF (VF(+) group: 10 male subjects) and without VF (VF(-) group: 27 male subjects) and 20 control subjects. Genetic analysis of SCN5A was performed in all 37 BrS patients. The relationships between QT, QTp, Tp-e, and RR intervals were obtained from Holter recordings as first linear regression lines, and the slopes of QT/RR, QTp/RR, and Tp-e/RR linear regression lines as the sensitivity of rate-dependent repolarization dynamics were compared. RESULTS: QT/RR and Tp-e/RR slopes showed loss of a rate-dependent property in the VF(+) group compared with those in the VF(-) and control groups. There was no significant difference in QTp/RR slope among the VF(+), VF(-) and control groups. The Tp-e interval had a negative correlation with the RR interval in the VF(+) group and a positive correlation with the RR interval in the VF(-) and control groups. There was no significant difference in QT/RR, QTp/RR, and Tp-e/RR slopes between BrS patients with SCN5A mutation and those without SCN5A mutation. CONCLUSIONS: Loss of rate-dependent QT dynamics may be associated with occurrence of VF in BrS.

    DOI: 10.1016/j.hrthm.2009.04.037

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  • Epicardial ablation eliminates ventricular arrhythmias in an experimental model of Brugada syndrome. International journal

    Hiroshi Morita, Douglas P Zipes, Shiho T Morita, John C Lopshire, Jiashin Wu

    Heart rhythm   6 ( 5 )   665 - 71   2009.5

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    BACKGROUND: Although radiofrequency catheter ablation (RFCA) has been used to treat patients with Brugada syndrome (BS), it is difficult to eliminate polymorphic ventricular tachycardias (VTs) completely. OBJECTIVE: The purpose of this study was to determine the efficacy of RFCA in eliminating recurrent VTs in an experimental model of BS. METHODS: We optically mapped electrical activity on the epicardial (n = 9) or transmural (n = 8) surface in 17 arterially perfused canine right ventricle preparations. Using pinacidil (5 microM) and pilsicainide (5 microM), we induced a model of BS that showed spontaneous VT. We then applied RFCA to the earliest activation site of premature ventricular complexes (PVCs) in the epicardium (EPI) or endocardium (ENDO) of the RV. RESULTS: After induction of BS, the transmural electrocardiogram (ECG) showed BS-type ECG in association with prominent heterogeneity of action potential duration (APDs) within the EPI (APD: maximum 272 +/- 39 ms, minimum 200 +/- 39 ms, P < .01), but not within the ENDO. PVCs originated in the EPI region having short APDs and triggered functional reentry causing VT. Multiple epicardial foci of PVCs existed in each tissue (3.7 +/- 1.9 foci/tissue). RFCA at the earliest activation site of PVCs in the EPI disconnected the short and long APD regions and eliminated all PVCs and VTs, although APD heterogeneity still existed. All successful RFCA lesions were confined to the EPI. RFCA in the ENDO failed to eliminate VT or PVCs. CONCLUSION: These experimental observations suggest that RFCA applied to the EPI may be more effective than applied to the ENDO in eliminating VT in patients with BS.

    DOI: 10.1016/j.hrthm.2009.01.007

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  • Differential effects of cardiac sodium channel mutations on initiation of ventricular arrhythmias in patients with Brugada syndrome. International journal

    Hiroshi Morita, Satoshi Nagase, Daiji Miura, Aya Miura, Shigeki Hiramatsu, Takeshi Tada, Masato Murakami, Nobuhiro Nishii, Kazufumi Nakamura, Shiho T Morita, Takefumi Oka, Kengo F Kusano, Tohru Ohe

    Heart rhythm   6 ( 4 )   487 - 92   2009.4

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    BACKGROUND: Premature ventricular contractions (PVCs) do not occur frequently but can induce ventricular fibrillation (VF) in patients with Brugada syndrome. The effect of SCN5A mutation on the onset of ventricular arrhythmias is unknown. OBJECTIVE: The purpose of this study was to evaluate PVC morphology and onset of VF in patients with Brugada syndrome. METHODS: Morphology of PVCs was evaluated by 12-lead ECG in 32 patients with Brugada syndrome. Patients had spontaneous ventricular arrhythmia (n = 17) or sodium channel blocker-induced ventricular arrhythmia (n = 19). Patients were classified into two groups according to the existence of SCN5A mutation (22 mutation negative, 10 mutation positive). RESULTS: Patients without mutation often had PVCs of left bundle branch block (LBBB) morphology (82%), especially with inferior axis (77%). Patients with mutation had PVCs of both right bundle branch block (36%) and LBBB (64%) morphologies. Only two patients with mutation had PVCs of LBBB, inferior-axis morphology. CONCLUSION: Patients without SCN5A mutation often had PVCs of LBBB, inferior-axis morphology, suggesting a right ventricular outflow tract origin. Patients with SCN5A mutations had PVCs that originated from both the right and left ventricles.

    DOI: 10.1016/j.hrthm.2009.01.031

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  • Fragmented QRS as a marker of conduction abnormality and a predictor of prognosis of Brugada syndrome. International journal

    Hiroshi Morita, Kengo F Kusano, Daiji Miura, Satoshi Nagase, Kazufumi Nakamura, Shiho T Morita, Tohru Ohe, Douglas P Zipes, Jiashin Wu

    Circulation   118 ( 17 )   1697 - 704   2008.10

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    BACKGROUND: Conduction abnormalities serve as a substrate for ventricular fibrillation (VF) in patients with Brugada syndrome (BS). Signal-averaged electrograms can detect late potentials, but the significance of conduction abnormalities within the QRS complex is still unknown. The latter can present as multiple spikes within the QRS complex (fragmented QRS [f-QRS]). We hypothesized that f-QRS could indicate a substrate for VF and might predict a high risk of VF for patients with BS. METHODS AND RESULTS: In study 1, we analyzed the incidence of f-QRS in 115 patients with BS (13 resuscitated from VF, 28 with syncope, and 74 asymptomatic). f-QRS was observed in 43% of patients, more often in the VF group (incidence of f-QRS: VF 85%, syncope 50%, and asymptomatic 34%, P<0.01). SCN5A mutations occurred more often in patients with f-QRS (33%) than in patients without f-QRS (5%). In patients with syncope or VF, only 6% without f-QRS experienced VF during follow-up (43+/-25 months), but 58% of patients with f-QRS had recurrent syncope due to VF (P<0.01). In study 2, to investigate the mechanism of f-QRS, we studied in vitro models of BS in canine right ventricular tissues (n=4) and optically mapped multisite action potentials. In the experimental model of BS, ST elevation resulted from a large phase 1 notch of the action potential in the epicardium, and local epicardial activation delay reproduced f-QRS in the transmural ECG. CONCLUSIONS: f-QRS appears to be a marker for the substrate for spontaneous VF in BS and predicts patients at high risk of syncope.

    DOI: 10.1161/CIRCULATIONAHA.108.770917

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  • Novel SCN5A Mutations and SNP in Patients with Brugada Syndrome

    Kazufumi Nakamura, Daiji Miura, Kaoru Kobayashi, Mamoru Ouchida, Kenji Shimizu, Iori Ohmori, Nobuhiro Nishii, Satoshi Nagase, Hiroshi Morita, Yoshiki Hata, Takefumi Oka, Kengo Kusano, Tohru Ohe

    CIRCULATION   118 ( 18 )   S981 - S981   2008.10

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  • 特発性2方向性心室頻拍の臨床電気生理学的機序の検討

    杉山 洋樹, 森田 宏, 三浦 大志, 永瀬 聡, 中村 一文, 岡 岳文, 草野 研吾, 大江 透

    心電図   28 ( 5 )   480 - 480   2008.10

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  • Brugada症候群患者における心室性不整脈の発生とSCN5A変異の関連

    森田 宏, 三浦 大志, 中村 一文, 永瀬 聡, 草野 研吾, 大江 透

    心電図   28 ( 5 )   484 - 484   2008.10

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  • Brugada症候群におけるICD作動の予測因子

    西井 伸洋, 森田 宏, 平松 茂樹, 多田 毅, 村上 正人, 三浦 大志, 永瀬 聡, 中村 一文, 岡 岳文, 大江 透, 草野 研吾

    心電図   28 ( 5 )   489 - 489   2008.10

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  • The QT syndromes: long and short. International journal

    Hiroshi Morita, Jiashin Wu, Douglas P Zipes

    Lancet (London, England)   372 ( 9640 )   750 - 63   2008.8

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    This Seminar presents the most recent information about the congenital long and short QT syndromes, emphasising the varied genotype-phenotype association in the ten different long QT syndromes and the five different short QT syndromes. Although uncommon, these syndromes serve as a Rosetta stone for the understanding of inherited ion-channel disorders leading to life-threatening cardiac arrhythmias. Ionic abnormal changes mainly affecting K(+), Na(+), or Ca(2+) currents, which either prolong or shorten ventricular repolarisation, can create a substrate of electrophysiological heterogeneity that predisposes to the development of ventricular tachyarrhythmias and sudden death. The understanding of the genetic basis of the syndromes is hoped to lead to genetic therapy that can restore repolarisation. Presently, symptomatic individuals are generally best treated with an implantable cardioverter defibrillator. Clinicians should be aware of these syndromes and realise that drugs, ischaemia, exercise, and emotions can precipitate sudden death in susceptible individuals.

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  • Repolarization heterogeneity in the right ventricular outflow tract: correlation with ventricular arrhythmias in Brugada patients and in an in vitro canine Brugada model. International journal

    Hiroshi Morita, Douglas P Zipes, Kengo Fukushima-Kusano, Satoshi Nagase, Kazufumi Nakamura, Shiho T Morita, Tohru Ohe, Jiashin Wu

    Heart rhythm   5 ( 5 )   725 - 33   2008.5

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    BACKGROUND: Brugada syndrome (BrS) is characterized by repolarization abnormality with ST-segment elevation in the right ventricular outflow tract (RVOT). OBJECTIVE: Although action potential (AP) heterogeneity is associated with induction of ventricular arrhythmias (VA) in BrS, clinical evidence and its experimental correlations are still absent and are the focus of this study. METHODS: We evaluated repolarization heterogeneity in 15 patients with BrS using body surface mapping and in 8 pairs of isolated canine RVOT and right ventricular anteroinferior (RVAI) preparations having drug-induced BrS using optical mapping. RESULTS: Patients had large J-ST-segment elevation and long QT interval in the RVOT at baseline. Administration of pilsicainide (1 mg/kg) exaggerated J-ST-segment elevation, caused simultaneous long and short QT intervals in the RVOT, and induced polymorphic ventricular tachycardia (VT) and T wave alternans (TWA). Dispersion of QT within the RVOT after pilsicainide was greater in patients that had syncope or ventricular fibrillation than those that did not. Ventricular arrhythmias originated from the RVOT along with local electrocardiogram changes and TWA. Repolarization heterogeneity was much less in areas outside the RVOT. Inducing BrS increased AP heterogeneity (with and without spike-and-dome) within the RVOT epicardium. Phase 2 reentry and TWA originated from the epicardium in 88% and 50% of RVOT preparations, respectively. In contrast, the RVOT endocardium and RVAI had little AP heterogeneity, with neither reentry nor TWA. CONCLUSION: The instability and heterogeneity of repolarization within the epicardium of the RVOT seem to be associated with arrhythmogenesis in both patients and in the in vitro tissue models of BrS.

    DOI: 10.1016/j.hrthm.2008.02.028

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  • イオンチャネル病のUp-to-date Anderson-Tawil症候群の心電図異常および不整脈発生の機序の検討

    森田 宏, 谷 義則, 永瀬 聡, 三浦 大志, 杉山 洋樹, 中村 一文, 草野 研吾, 大江 透, ザイペス・ダグラス, 古川 哲史

    Journal of Arrhythmia   24 ( Suppl. )   98 - 98   2008.4

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  • 精巣摘出によりBrugada型心電図が消失した心筋ナトリウムチャネル遺伝子変異を有する1症例

    森田 宏, 草野 研吾, 永瀬 聡, 三浦 大志, 中村 一文, 大江 透

    Journal of Arrhythmia   24 ( Suppl. )   185 - 185   2008.4

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  • Atrial fibrillation in patients with Brugada syndrome relationships of gene mutation, electrophysiology, and clinical backgrounds. International journal

    Kengo F Kusano, Makiko Taniyama, Kazufumi Nakamura, Daiji Miura, Kimikazu Banba, Satoshi Nagase, Hiroshi Morita, Nobuhiro Nishii, Atsuyuki Watanabe, Takeshi Tada, Masato Murakami, Kohei Miyaji, Shigeki Hiramatsu, Koji Nakagawa, Masamichi Tanaka, Aya Miura, Hideo Kimura, Soichiro Fuke, Wakako Sumita, Satoru Sakuragi, Shigemi Urakawa, Jun Iwasaki, Tohru Ohe

    Journal of the American College of Cardiology   51 ( 12 )   1169 - 75   2008.3

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    OBJECTIVES: The goal of our work was to examine the relationships of atrial fibrillation (AF) with genetic, clinical, and electrophysiological backgrounds in Brugada syndrome (BrS). BACKGROUND: Atrial fibrillation is often observed in patients with BrS and indicates that electrical abnormality might exist in the atrium as well as in the ventricle. SCN5A, a gene encoding the cardiac sodium channel, has been reported to be causally related to BrS. However, little is known about the relationships of atrial arrhythmias with genetic, clinical, and electrophysiological backgrounds of BrS. METHODS: Seventy-three BrS patients (49 +/- 12 years of age, men/women = 72/1) were studied. The existence of SCN5A mutation and clinical variables (syncopal episode, documented ventricular fibrillation [VF], and family history of sudden death) were compared with spontaneous AF episodes. Genetic and clinical variables were also compared with electrophysiologic (EP) parameters: atrial refractory period, interatrial conduction time (CT), repetitive atrial firing, and AF induction by atrial extra-stimulus testing. RESULTS: Spontaneous AF occurred in 10 (13.7%) of the BrS patients and SCN5A mutation was detected in 15 patients. Spontaneous AF was associated with higher incidence of syncopal episodes (60.0% vs. 22.2%, p < 0.03) and documented VF (40.0% vs. 14.3%, p < 0.05). SCN5A mutation was associated with prolonged CT (p < 0.03) and AF induction (p < 0.05) in EP study, but not related to the spontaneous AF episode and other clinical variables. In patients with documented VF, higher incidence of spontaneous AF (30.8% vs. 10.0%, p < 0.05), AF induction (53.8% vs. 20.0%, p < 0.03), and prolonged CT was observed. CONCLUSIONS: Spontaneous AF and VF are closely linked clinically and electrophysiologically in BrS patients. Patients with spontaneous AF have more severe clinical backgrounds in BrS. SCN5A mutation is associated with electrical abnormality but not disease severity.

    DOI: 10.1016/j.jacc.2007.10.060

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  • Longer repolarization in the epicardium at the right ventricular outflow tract causes type 1 electrocardiogram in patients with Brugada syndrome. International journal

    Satoshi Nagase, Kengo Fukushima Kusano, Hiroshi Morita, Nobuhiro Nishii, Kimikazu Banba, Atsuyuki Watanabe, Shigeki Hiramatsu, Kazufumi Nakamura, Satoru Sakuragi, Tohru Ohe

    Journal of the American College of Cardiology   51 ( 12 )   1154 - 61   2008.3

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    OBJECTIVES: We examined the relationship between repolarization abnormality and coved-type ST-segment elevation with terminal inverted T-wave (type 1 electrocardiogram [ECG]) in patients with Brugada syndrome (BrS). BACKGROUND: Recent experimental studies have suggested that accentuation of the right ventricular action potential (AP) notch preferentially prolongs epicardial AP causing inversion of the T-wave. METHODS: In 19 patients with BrS and 3 control subjects, activation-recovery intervals (ARIs) and repolarization times (RTs) in the epicardium and endocardium were directly examined with the use of local unipolar electrograms at the right ventricular outflow tract. Surface ECG, ARI, and RT were examined before and after administration of pilsicainide. RESULTS: Type 1 ECG was observed in 10 of the 19 BrS patients before the administration of pilsicainide and in all of the 19 patients after the administration of pilsicainide. We found that ARI and RT in the epicardium were shorter than those in the endocardium in all 9 BrS patients without type 1 ECG under baseline conditions and in all control subjects regardless of pilsicainide administration. However, longer epicardial ARI than endocardial ARI was observed in 8 of the 10 BrS patients manifesting type 1 ECG under baseline conditions and in all of the BrS patients after the administration of pilsicainide. Also, epicardial RT was longer than endocardial RT in all patients manifesting type 1 ECG regardless of pilsicainide administration. CONCLUSIONS: Our data provide support for the hypothesis that the negative T-wave associated with type 1 BrS ECG is due to a preferential prolongation of the epicardial AP secondary to accentuation of the AP notch in the region of the right ventricular outflow tract.

    DOI: 10.1016/j.jacc.2007.10.059

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  • Clinical significance of macroscopic T-wave alternans after sodium channel blocker administration in patients with Brugada syndrome. International journal

    Takeshi Tada, Kengo Fukushima Kusano, Satoshi Nagase, Kimikazu Banba, Daiji Miura, Nobuhiro Nishii, Atsuyuki Watanabe, Kazufumi Nakamura, Hiroshi Morita, Tohru Ohe

    Journal of cardiovascular electrophysiology   19 ( 1 )   56 - 61   2008.1

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    INTRODUCTION: Macroscopic T-wave alternans (TWA) is sometimes observed after sodium channel blocker administration in patients with Brugada syndrome (BS), but little is known about the association between occurrence of TWA and clinical characteristics in BS patients. We investigated the association between spontaneous ventricular fibrillation (VF) occurrence and TWA after pilsicainide, a sodium channel blocker administration in BS patients. METHODS AND RESULTS: We administered pilsicainide at a dose of 1 mg/kg to 77 BS patients (76 males and one female; mean age, 48.4 years) and examined the association between TWA after pilsicainide administration and clinical characteristics, including age, spontaneous VF, syncope, family history of sudden death, spontaneous coved ST elevation, late potentials (LP), induction of VF by programmed electrical stimulation, and SCN5A mutation. None of the patients had TWA before pilsicainide administration, but TWA became apparent in 17 (22.1%) of the patients after pilsicainide administration. Patients with TWA had a significantly higher incidence of spontaneous VF (52.9% vs 8.3%, P < 0.001) and syncope (58.8% vs 26.7%, P < 0.05) than did patients without TWA. Then, we focused on the association between spontaneous VF and clinical characteristics. Patients with spontaneous VF had a significantly higher incidence of TWA (64.3% vs 12.7%, P < 0.001) and LP positive (92.9% vs 56.5%, P < 0.01) than did patients without spontaneous VF. In multivariate analysis, TWA (P = 0.001) and LP (P = 0.047) appeared as the independent predictor for spontaneous VF. CONCLUSION: TWA after pilsicainide administration is associated with a high risk of clinical VF in patients with BS.

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  • Anti-KCNH2 antibody-induced long QT syndrome: novel acquired form of long QT syndrome. International journal

    Kazufumi Nakamura, Yusuke Katayama, Kengo F Kusano, Kayo Haraoka, Yoshinori Tani, Satoshi Nagase, Hiroshi Morita, Daiji Miura, Yoshihisa Fujimoto, Tetsushi Furukawa, Kazuo Ueda, Yoshiyasu Aizawa, Akinori Kimura, Yoshihisa Kurachi, Tohru Ohe

    Journal of the American College of Cardiology   50 ( 18 )   1808 - 9   2007.10

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  • Anti-KCNH2 antibody-induced long QT syndrome - Novel acquired form of LQT syndrome Reviewed

    Kazufumi Nakamura, Yusuke Katayama, Kaye Haraoka, Yoshinori Tani, Daiji Miura, Hiroshi Morita, Kengo F. Kusano, Tetsushi Furukawa, Akinori Kimura, Yoshihisa Kurachi, Satoshi Nagase, Tohru Ohe

    CIRCULATION   116 ( 16 )   477 - 477   2007.10

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  • Mechanism of U wave and polymorphic ventricular tachycardia in a canine tissue model of Andersen-Tawil syndrome. International journal

    Hiroshi Morita, Douglas P Zipes, Shiho T Morita, Jiashin Wu

    Cardiovascular research   75 ( 3 )   510 - 8   2007.8

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    OBJECTIVE: Andersen-Tawil syndrome (ATS) is a channelopathy affecting inward rectifier potassium I(K1) with QT prolongation, large U waves, and frequent ventricular tachycardia (VT). Although ATS is clinically defined and genetically identified, its electrophysiological mechanism is still unclear, and thus, was the subject of the current study. METHODS AND RESULTS: We replicated the major electrophysiological features of ATS with cesium chloride (CsCl, at I(K1) blockade concentration of 5-10 mmol/l) in 23 isolated canine left ventricular tissues perfused arterially with Tyrode's solution having normal or low potassium concentrations, [K(+)](o). We mapped action potentials (APs) on the cut-exposed transmural surface of the wedges in control, after CsCl, and CsCl with 0.15 mumol/l isoproterenol (CsCl+ISP). CsCl delayed late phase 3 repolarization and prolonged the duration of the AP, more so during low [K(+)](o) perfusion. Rapid pacing induced delayed afterdepolarizations (DADs) in all low [K(+)](o) and in 71% of normal [K(+)](o) preparations after CsCl treatment. Addition of ISP induced DADs in all preparations. DADs originated in mid-to-endocardium, and initiated VT after CsCl+ISP. Migration of DAD-VT foci resulted in multifocal VT. Alternating DADs at 2 foci resulted in bidirectional VT. There were more foci and longer durations of VT at low [K(+)](o) than at normal [K(+)](o). Delayed late phase 3 repolarization of APs and DADs generated U waves. Verapamil abolished all DADs and VT. CONCLUSIONS: CsCl blockade of I(K1) produced a ventricular wedge model of ATS. Suppressing I(K1) generated U waves by delaying late repolarization of APs and creating DADs, and promoted polymorphic VT by triggering DADs at multiple shifting sites.

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  • Analysis of action potentials in the canine ventricular septum: no phenotypic expression of M cells. International journal

    Shiho T Morita, Douglas P Zipes, Hiroshi Morita, Jiashin Wu

    Cardiovascular research   74 ( 1 )   96 - 103   2007.4

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    OBJECTIVE: Transmural heterogeneity in the ventricular free wall, enhanced by the midmyocardial long action potential duration (APD) of M cells, plays an important role in the arrhythmogenesis of long QT syndrome. Although we observed dynamic expression of M cell phenotypes in the canine ventricular free wall, it is still unclear whether similar phenomena are present in the interventricular septum. This study evaluated transmural heterogeneity of APD in the septum. METHODS: We isolated and perfused 22 canine septal preparations through the septal branch of the anterior descending coronary artery, and optically mapped 256 channels of action potentials on their cut-exposed transseptal surfaces before and after treatment with sotalol (I(Kr) blocker), anemone toxin II (ATX-II, which slows the inactivation of I(Na)), or drug-free state in 6, 9, and 22 preparations, respectively. The preparations were paced from the left ventricular endocardium at cycle lengths of 500, 1000, 2000, and 4000 ms. RESULTS: We observed progressively lengthening of APD across the septum from the right ventricular to the left ventricular endocardium without a midmyocardial maximum under all conditions. All action potentials had minor phase-1 notches, resembling the endocardial action potential in the ventricular free wall. Increasing cycle lengths and concentrations of sotalol and ATX-II prolonged APD without midmyocardial preference and increased the transseptal dispersion of APDs. CONCLUSIONS: Canine interventricular septal action potentials are similar in shape to the endocardial action potentials in the ventricular free wall, with smooth transseptal transition in APD. We found no phenotypical expression of M cells in the canine interventricular septum.

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  • Temperature modulation of ventricular arrhythmogenicity in a canine tissue model of Brugada syndrome. International journal

    Hiroshi Morita, Douglas P Zipes, Shiho T Morita, Jiashin Wu

    Heart rhythm   4 ( 2 )   188 - 97   2007.2

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    BACKGROUND: Fever promotes ventricular arrhythmias in Brugada syndrome (BrS). Hypothermia can induce BrS electrocardiogram (ECG) and arrhythmia. However, the mechanisms are unclear. OBJECTIVE: We evaluated the hypothesis that pathological temperatures promoted arrhythmogenesis by modulating the spatial heterogeneity and functional dynamics of right ventricular electrophysiological activity. METHODS: We mapped action potentials (APs) on the epicardial or cut-exposed transmural surfaces and recorded transmural ECGs in 27 arterially perfused canine right ventricular preparations before and after inducing BrS at 32 degrees C, 36.5 degrees C, and 40 degrees C. RESULTS: We observed major intraepicardial dispersion of AP duration (APD) and reversal of transmural gradient of APD in association with manifestation of BrS at 36.5 degrees C. Reducing the temperature to 32 degrees C prolonged APDs and enhanced the phase 1 notch of epicardial APs, while 40 degrees C caused opposite changes. Prominent phase 2 domes of APs frequently led to spontaneous premature ventricular activations (PVAs), which conducted to surrounding regions having shorter APDs. Longer APDs at 32 degrees C and 36.5 degrees C frequently blocked reentry, although they promoted PVA, while shortened APDs at 40 degrees C facilitated reentrant ventricular tachycardia. During bradycardia (2,000 ms), the J-ST elevation in the ECG was enhanced at 32 degrees C and attenuated at 40 degrees C. Rapid pacing (500 ms) eliminated the dome of epicardial APs and enhanced J-ST elevation at each temperature. Blocking the transient outward current, I(to), with 4-aminopyridine reduced J-ST elevation and eliminated the PVA and reentry. CONCLUSIONS: In this BrS model, prolongation and increased dispersion of APDs promoted spontaneous activation during hypothermia, while APD abbreviation facilitated reentry during hyperthermia. I(to) mediated the arrhythmogenicity.

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  • Differences in arrhythmogenicity between the canine right ventricular outflow tract and anteroinferior right ventricle in a model of Brugada syndrome. International journal

    Hiroshi Morita, Douglas P Zipes, Shiho T Morita, Jiashin Wu

    Heart rhythm   4 ( 1 )   66 - 74   2007.1

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    BACKGROUND: The Brugada syndrome is characterized by ST-segment elevation on the ECG, especially in the right precordial leads sensitive to the right ventricular outflow tract (RVOT). OBJECTIVES: The purpose of this study was to evaluate the hypothesis that right ventricular electrophysiologic heterogeneity caused arrhythmogenicity in the Brugada syndrome. METHODS: Action potentials (APs) were mapped on the epicardium of 14 RVOT preparations and on the transmural surfaces of 15 pairs of RVOT and right ventricular anteroinferior (RVAI) preparations isolated from canine hearts. Brugada ECG and arrhythmias were induced with pilsicainide (2.5-12.5 micromol/L), pinacidil (1.25-12.5 micromol/L), and terfenadine (2.0 micromol/L). RESULTS: Low doses of drugs elevated the J-ST segment and induced APs with both short and long action potential durations (APDs) in contiguous RVOT epicardial regions. In addition, APs in the RVOT had a larger phase 1 notch and longer APD than in RVAI. The longest APDs were in the epicardium in RVOT but in the endocardium in RVAI regions. High doses of drugs eliminated the phase 2 dome of the AP and abbreviated APDs in the epicardium but not in endocardium and reduced the epicardial heterogeneity of APs but increased the transmural gradient of APD in 14 (93%) of the RVOT preparations. In contrast, abbreviations of epicardial APDs occurred in only 4 (27%) of the RVAI preparations. Ventricular tachycardia occurred more frequently in the RVOT (47%) than in paired RVAI preparations (7%). Blocking the transient outward current reduced the heterogeneity of APs and eliminated arrhythmogenicity in all preparations. CONCLUSION: Compared with the RVAI region, the RVOT has greater electrophysiologic heterogeneity that contributes to arrhythmogenicity in this model of Brugada syndrome.

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  • Steroid therapy improves atrioventricular conduction disturbance but not ventricular arrhythmia in active phase of cardiac sarcoidosis Reviewed

    Kimikazu Banba, Kengo Kusano, Kazufumi Nakamura, Hiroshi Morita, Aiko Ogawa, Atsuyuki Watanabe, Nobuhiro Nishii, Satoshi Nagase, Satoru Sakuragi, Tohru Ohe

    CIRCULATION   114 ( 18 )   469 - 469   2006.10

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  • T wave alternans in an in vitro canine tissue model of Brugada syndrome. International journal

    Hiroshi Morita, Douglas P Zipes, John Lopshire, Shiho T Morita, Jiashin Wu

    American journal of physiology. Heart and circulatory physiology   291 ( 1 )   H421-8   2006.7

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    Macroscopic T wave alternans (TWA) associated with increased occurrence of ventricular arrhythmias has been reported in patients with Brugada syndrome. However, the mechanisms in this syndrome are still unclear. We evaluated the hypothesis that TWA in Brugada syndrome was caused by the dynamic instability and heterogeneity of action potentials (APs) in the right ventricle. Using an optical mapping system, we mapped APs on the epicardium or transmural surfaces of 28 isolated and arterially perfused canine right ventricular preparations having drug-induced Brugada syndrome (in micromol/l: 2.5-15 pinacidil, 5.0 terfenadine, and 5.0-13 pilsicainide). Bradycardia at cycle length (CL) of 2,632 +/- 496 ms (n = 19) induced alternating deep and shallow T waves in the transmural electrocardiogram. Compared with the shallow T waves, deep T waves were associated with epicardial APs having longer durations and larger domes. Adjacent regions having APs with alternating domes, with constant domes, and without domes coexisted simultaneously in the epicardium and caused TWA. In contrast to the alternating epicardial APs, midmyocardial and endocardial APs did not change during TWA. Alternans could be terminated by rapid (CL: 529 +/- 168 ms, n = 7) or very slow (CL: 3,000 ms, n = 7) pacing. The heterogeneic APs during TWA augmented the dispersion of repolarization both within the epicardium and from the epicardium to the endocardium and caused phase 2 reentry. In this drug-induced model of Brugada syndrome, heterogeneic AP contours and dynamic alternans in the dome of right ventricular epicardial, but not midmyocardial or endocardial, APs caused TWA and heightened arrhythmogenicity in part by increasing the dispersion of repolarization.

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  • Low-dose isoproterenol for repetitive ventricular arrhythmia in patients with Brugada syndrome. International journal

    Atsuyuki Watanabe, Kengo Fukushima Kusano, Hiroshi Morita, Daiji Miura, Wakako Sumida, Shigeki Hiramatsu, Kimikazu Banba, Nobuhiro Nishii, Satoshi Nagase, Kazufumi Nakamura, Satoru Sakuragi, Tohru Ohe

    European heart journal   27 ( 13 )   1579 - 83   2006.7

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    AIMS: Arrhythmic storm or repetitive ventricular arrhythmia (VA) has been occasionally observed in Brugada syndrome (BS). A beta-adrenergic stimulator [isoproterenol (ISP)] has been reported to suppress this arrhythmic storm in sporadic cases. Accordingly, we investigated the antiarrhythmic effects of ISP infusion in consecutive BS patients with arrhythmic storm or repetitive VA. METHODS AND RESULTS: Seven BS patients with arrhythmic storm were studied. Intravenous ISP was administered as a bolus injection (1-2 microg), followed by continuous infusion (0.15 microg/min). Arrhythmic storm or repetitive VA was suppressed immediately after the bolus administration of ISP, which was followed by continuous infusion of low-dose ISP for 1-3 days. In all patients, ST-elevation decreased in right precordial leads. In six of the seven patients, VA subsided after the discontinuance of ISP. RR interval was shortened and ST-elevation in right precordial leads was decreased after ISP bolus injection. ST-elevation in right precordial leads remained decreased during continuous ISP infusion, whereas the RR interval returned to the control level. CONCLUSION: Continuous administration of low-dose ISP may be effective for the suppression of repetitive VA occurrence in patients with BS.

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  • [Long QT syndrome].

    Atsuyuki Watanabe, Kazufumi Nakamura, Hiroshi Morita, Kengo Fukushima Kusano, Tohru Ohe

    Nihon rinsho. Japanese journal of clinical medicine   63 ( 7 )   1171 - 7   2005.7

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    The long QT syndrome (LQTS) is characterized by prolongation of the QT interval, causing torsade de pointes and sudden cardiac death. This syndrome can be divided into idiopathic (congenital) and acquired forms. The idiopathic form is a familial disorder that can be associated with sensorineural deafness (Jervell and Lange--Nielsen syndrome, autosomal recessive) or normal hearing (Romano--Ward syndrome, autosomal dominant). The acquired form has a long QT interval caused by various drugs such as quinidine sotalol and dofetilide, also by noncardiovascular drugs such as antihistamine, antibiotics, antipsychotics and others. Also, the QT interval is prolonged by electrolyte abnormalities such as hypokalemia and hypomagnesemia, central nervous system lesions, significant bradyarrhythmias, cardiac ganglionitis, mitral valve prolapse and probucol. DNA variants appearing to predispose to drug-associated acquired long QT syndrome have been reported in congenital long QT.

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  • カルシウム拮抗薬(CCB)の抗炎症作用についての検討

    三浦 龍志, 中村 一文, 三浦 大志, 三浦 綾, 久松 研一, 橋本 克史, 永瀬 聡, 森田 宏, 草野 研吾, 齋藤 博則, 江森 哲郎, 大江 透

    Circulation Journal   69 ( Suppl.II )   805 - 805   2005.4

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  • SCN5A遺伝子異常(R282H)を認めたBrugada症候群の一家系

    中村 一文, 三浦 大志, 平松 茂樹, 湯本 晃久, 江森 哲郎, 森田 宏, 渡辺 敦之, 永瀬 聡, 齋藤 博則, 草野 研吾, 西井 伸洋, 大江 透, 長野 仁, 神山 憲王

    Circulation Journal   69 ( Suppl.II )   798 - 798   2005.4

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  • Failure of disopyramide to improve right ventricular outflow tract obstruction after living-donor lobar lung transplantation.

    Katsumasa Miyaji, Hiromi Matsubara, Masahito Kajiya, Yoshinori Tani, Kazufumi Nakamura, Hiroshi Morita, Tetsuro Emori, Hiroshi Date, Tohru Ohe

    Circulation journal : official journal of the Japanese Circulation Society   68 ( 11 )   1084 - 7   2004.11

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    Right ventricular (RV) outflow tract obstruction (RVOTO) is an uncommon complication of lung transplantation in patients with pulmonary hypertension (PH) and both medical management and surgical intervention are required. A 28-year-old female with primary PH was referred and because she did not respond to medical treatment, living-donor lobar lung transplantation was performed. The operation was successful, but dyspnea and exercise intolerance developed during rehabilitation and transthoracic echocardiography revealed RVOTO. Intravenous disopyramide during cardiac catheterization reduced the pressure gradient from 35 mmHg to 16 mmHg without decreasing RV systolic pressure. However, electrical and hemodynamic parameters were adversely affected by disopyramide and thus, after cardiac catheterization, administration of fluid and a low dose of atenolol was started, and her symptoms improved. Transthoracic echocardiography showed improvement in the RVOTO. This case suggests that disopyramide should be avoided for patients with RVOTO following lung transplantation and that other negative inotropic agents, such as beta-blockers, are more effective for relief of RVOTO.

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  • Differences between flow profiles of pulmonary vein anastomoses affected by peripheral atelectasis in cadaveric and bilateral living-donor lobar lung transplantations. International journal

    Katsumasa Miyaji, Hiromi Matsubara, Kazufumi Nakamura, Takeshi Maruo, Hiroshi Morita, Hironori Saito, Kengo F Kusano, Tetsuro Emori, Keiji Goto, Hiroshi Date, Tohru Ohe

    Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography   17 ( 9 )   1003 - 4   2004.9

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    We report two cases of peripheral atelectasis during cadaveric and living-donor lobar lung transplantation, which had different effects on the flow profile of pulmonary vein (PV) anastomoses. In the patient who underwent living-donor lobar lung transplantation, we detected the increase in the velocity of blood flow through the left PV anastomosis by intraoperative transesophageal echocardiography. Then peripheral atelectasis occurred in the transplanted left lung lobe. On the other hand, in the patient who underwent cadaveric bilateral lung transplantation, peripheral atelectasis occurred, but no changes in velocities of blood flow through PV anastomoses were detected by intraoperative transesophageal echocardiography. This difference may have been caused by the difference in sizes of pulmonary beds of transplanted grafts. These findings indicate the necessity of careful monitoring of PV anastomoses, especially in cases of living-donor lobar lung transplantation.

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  • Effect of a kink in unilateral pulmonary artery anastomosis on velocities of blood flow through bilateral pulmonary vein anastomoses in living-donor lobar lung transplantation. International journal

    Katsumasa Miyaji, Kazufumi Nakamura, Takeshi Maruo, Hiroshi Morita, Hironori Saito, Tetsuro Emori, Keiji Goto, Hiroshi Date, Tohru Ohe

    Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography   17 ( 9 )   998 - 9   2004.9

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    Intraoperative transesophageal echocardiography is generally performed to detect vascular complications during lung transplantation. We report a case with a kink in pulmonary artery (PA) anastomosis suggested by an abnormal flow profile of pulmonary vein (PV) anastomoses during living-donor lobar lung transplantation. During the transplantation, velocity of blood flow through the right PV anastomosis showed abnormal elevation. Then, the patient's PA pressure elevated abnormally and a kink in the left PA anastomosis was found. Careful monitoring of PV anastomoses may enable detection of not only an abnormality of PV anastomoses but also that of PA anastomoses, especially in living-donor lobar lung transplantation.

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  • Relationships between depolarization abnormality and repolarization abnormality in patients with Brugada syndrome: using body surface signal-averaged electrocardiography and body surface maps. International journal

    Kenichi Hisamatsu, Kengo Fukushima Kusano, Hiroshi Morita, Shiho Takenaka, Satoshi Nagase, Kazufumi Nakamura, Tetsuro Emori, Hiromi Matsubara, Hiroshi Mikouchi, Yoshitomo Nishizaki, Tohru Ohe

    Journal of cardiovascular electrophysiology   15 ( 8 )   870 - 6   2004.8

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    INTRODUCTION: Repolarization and depolarization abnormalities have been reported to be related to Brugada syndrome. METHODS AND RESULTS: We evaluated the relationships between repolarization abnormality and depolarization abnormality using 48-lead unipolar signal-averaged electrocardiograms and 87-lead unipolar body surface maps in 15 patients with Brugada-type ECGs. Data were compared with those from healthy control subjects (n = 5) and within subgroups of Brugada syndrome with (n = 8) and without (n = 7) ventricular arrhythmias (VA) induced by programmed electrical stimulation (PES). Eighty-seven-lead body surface maps were recorded, and potential maps were constructed to evaluate elevation of the ST segment 20 ms after the J point. Forty-eight-lead signal-averaged ECGs were recorded, and isochronal maps of duration of the delayed potential (dDP) were constructed to evaluate the dDP in each lead. Potential maps showed that patients with Brugada-type ECG, especially those with VA induced by programmed electrical stimulation, had greater elevation of the ST segment in the right ventricular outflow tract, especially at E5. Isochronal maps of dDP in the Brugada-type ECG group showed that maximum dDP was located at E5 and that the area with long dDP was larger than that in the control subjects. The dDPs at E7, E5, F7, and F5 in the VA-inducible group were significantly longer than those in the VA-noninducible group. These results showed that the location of greater elevation in the ST segment coincided with the location of longer dDP. CONCLUSION: Repolarization abnormality and depolarization abnormality in the walls of both ventricles, especially in the right ventricular outflow tract, are related to the VA of Brugada syndrome.

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  • Significance of the level of monocyte chemoattractant protein-1 in human atherosclerosis.

    Kengo Fukushima Kusano, Kazufumi Nakamura, Hitoshi Kusano, Nobuhiro Nishii, Kimikazu Banba, Tetsuya Ikeda, Katsushi Hashimoto, Mika Yamamoto, Hideki Fujio, Aya Miura, Keiko Ohta, Hiroshi Morita, Hironori Saito, Tetsuro Emori, Yoichi Nakamura, Isao Kusano, Tohru Ohe

    Circulation journal : official journal of the Japanese Circulation Society   68 ( 7 )   671 - 6   2004.7

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    BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1), a potent chemoattractant for monocytes, plays an important role in the earliest events of atherogenesis. However, direct evidence of the effects of MCP-1 on atherosclerosis in chronic hemodialysis (HD) patients has not been reported. METHODS AND RESULTS: The serum MCP-1 concentrations and the intimal - medial thickness (IMT) in the carotid arteries were measured in 42 non-diabetic chronic HD patients and 20 age-matched controls. The expression of MCP-1 was examined immunohistochemically in radial arterial tissues obtained from the HD patients. IMT and the serum concentration of MCP-1 in the HD patients were both significantly greater than in controls. Multiple regression analysis revealed that the serum concentration of MCP-1 was an independent factor influencing IMT. Tissue immunostaining showed that MCP-1 is expressed in both endothelial and smooth muscle cells and that its level of expression correlates with the serum concentration of MCP-1. CONCLUSIONS: An increase in MCP-1 may be an important factor in the progression of atherosclerosis in non-diabetic HD patients.

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  • Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. International journal

    Kazuo Ueda, Kazufumi Nakamura, Takeharu Hayashi, Natsuko Inagaki, Megumi Takahashi, Takuro Arimura, Hiroshi Morita, Yasushi Higashiuesato, Yuji Hirano, Michio Yasunami, Shuichi Takishita, Akira Yamashina, Tohru Ohe, Makoto Sunamori, Masayasu Hiraoka, Akinori Kimura

    The Journal of biological chemistry   279 ( 26 )   27194 - 8   2004.6

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    Hyperpolarization-activated cyclic nucleotide-gated channel 4 gene HCN4 is a pacemaker channel that plays a key role in automaticity of sinus node in the heart, and an HCN4 mutation was reported in a patient with sinus node dysfunction. Expression of HCN4 in the heart is, however, not confined to the sinus node cells but is found in other tissues, including cells of the conduction system. On the other hand, mutations in another cardiac ion channel gene, SCN5A, also cause sinus node dysfunction as well as other cardiac arrhythmias, including long QT syndrome, Brugada syndrome, idiopathic ventricular fibrillation, and progressive cardiac conduction disturbance. These observations imply that HCN4 abnormalities may be involved in the pathogenesis of various arrhythmias, similar to the SCN5A mutations. In this study, we analyzed patients suffering from sinus node dysfunction, progressive cardiac conduction disease, and idiopathic ventricular fibrillation for mutations in HCN4. A missense mutation, D553N, was found in a patient with sinus node dysfunction who showed recurrent syncope, QT prolongation in electrocardiogram, and polymorphic ventricular tachycardia, torsade de pointes. In vitro functional study of the D553N mutation showed a reduced membranous expression associated with decreased If currents because of a trafficking defect of the HCN4 channel in a dominant-negative manner. These data suggest that the loss of function of HCN4 is associated with sinus nodal dysfunction and that a consequence of pacemaker channel abnormality might underlie clinical features of QT prolongation and polymorphic ventricular tachycardia developed under certain conditions.

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  • Sinus node function in patients with Brugada-type ECG.

    Hiroshi Morita, Kengo Fukushima-Kusano, Satoshi Nagase, Kohei Miyaji, Shigeki Hiramatsu, Kimikazu Banba, Nobuhiro Nishii, Atsuyuki Watanabe, Mikio Kakishita, Shiho Takenaka-Morita, Kazufumi Nakamura, Hironori Saito, Tetsuro Emori, Tohru Ohe

    Circulation journal : official journal of the Japanese Circulation Society   68 ( 5 )   473 - 6   2004.5

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    BACKGROUND: Some studies have shown that patients with Brugada syndrome (BS) have atrioventricular conduction disturbance, but their sinus node function has not been evaluated. METHODS AND RESULTS: The patients group consisted of 59 male patients and 1 female patient with BS. Supraventricular and ventricular programmed electrical stimulation (PES) was performed. Ventricular fibrillation (VF) or sustained polymorphic ventricular tachycardia was induced by ventricular PES in 26 patients with BS (VF group), but was not induced in the other 34 patients (non-VF group). Sinus node function and conduction of the atrioventricular (AV) node in the control group, non-VF group and VF group were evaluated. Sinus node function was attenuated and the His - ventricle interval was prolonged in the VF group (corrected sinus node recovery time: 452+/-126 ms (VF group), 324+/-146 ms (non-VF group), Sino-atrial conduction time: 179+/-60 ms (VF group), 127+/-60 ms (non-VF group), His-ventricle interval: 41+/-9 ms (VF group), 35+/-8 ms (non-VF group)). CONCLUSION: The function of both the sinus node and AV node are attenuated in patients with PES-induced VF.

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  • Epoprostenol therapy decreases elevated circulating levels of monocyte chemoattractant protein-1 in patients with primary pulmonary hypertension.

    Hashimoto Katsushi, Nakamura Kazufumi, Fujio Hideki, Miyaji Katsumasa, Morita Hiroshi, Kusano Kengo, Date Hiroshi, Shimizu Nobuyoshi, Emori Tetsuro, Matsubara Hiromi, Ohe Tohru

    Circulation journal : official journal of the Japanese Circulation Society   68 ( 3 )   227 - 31   2004.3

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    BACKGROUND: Primary pulmonary hypertension (PPH) is a rare disease characterized by progressively increased resistance of the pulmonary arteries associated with vascular remodeling. Infiltration of inflammatory cells in affected vessels is a common pathological finding. Monocyte chemoattractant protein-1 (MCP-1) is recognized as a potent chemotactic and activating factor for monocytes and leukocytes, but its significance in PPH is unclear. METHODS AND RESULTS: Serum MCP-1 concentrations were measured in 16 PPH patients and the results were compared with those in 16 normal controls. MCP-1 concentrations in PPH patients (265.6+/-29.5 pg/ml) were significantly elevated compared with those in normal controls (119.6+/-6.9 pg/ml, p<0.0001). In 9 patients (3 men, 6 women; mean age, 29+/-3 years), repeated MCP-1 and hemodynamic measurements were performed prior to and during intravenous epoprostenol therapy. During a mean follow-up period of 7+/-1 months, MCP-1 concentrations were significantly reduced (288.8+/-122.8 to 185.9+/-117.5 pg/ml, p<0.01). CONCLUSIONS: Circulating MCP-1 concentrations are increased in PPH patients, but can alleviated by chronic intravenous epoprostenol therapy. The increase in MCP-1 might be one of the important factors responsible for the disease development in patients with PPH.

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  • Usefulness of body surface mapping to differentiate patients with Brugada syndrome from patients with asymptomatic Brugada syndrome.

    Kenichi Hisamatsu, Kengo Fukushima Kusano, Hiroshi Morita, Shiho Takenaka, Satoshi Nagase, Kazufumi Nakamura, Tetsuro Emori, Hiromi Matsubara, Tohru Ohe

    Acta medica Okayama   58 ( 1 )   29 - 35   2004.2

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    We attempted to determine the usefulness of body surface mapping (BSM) for differentiating patients with Brugada syndrome (BS) from patients with asymptomatic Brugada syndrome (ABS). Electrocardiograms (ECG) and BSM were recorded in 7 patients with BS and 35 patients with ABS. Following the administration of Ic antiarrhythmic drugs, BSM was recorded in 5 patients with BS and 16 patients with ABS. The maximum amplitudes at J0, J20, J40 and J60 were compared between the 2 groups, as were 3-dimensional maps. The maximum amplitudes at J0, J20 and J60 under control conditions were larger in patients with BS than in patients with ABS (P < 0.05). A three-dimensional map of the ST segments under control conditions in patients with BS showed a higher peak of ST elevation in the median precordium compared to that for patients with ABS. Increases in ST elevation at J20, J40 and J60 following drug administration were greater in patients with BS than in patients with ABS (P < 0.05). Evaluation of the change in amplitude of the ST segment at E5 caused by Ic drug administration was also useful for differentiating between the 2 groups. In conclusion, BSM was useful for differentiating patients with BS from those with ABS.

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  • Evaluation of the usefulness of recording the ECG in the 3rd intercostal space and prevalence of Brugada-type ECG in accordance with recently established electrocardiographic criteria.

    Kenichi Hisamatsu, Hiroshi Morita, Kengo Fukushima Kusano, Shiho Takenaka, Satoshi Nagase, Kazufumi Nakamura, Tetsuro Emori, Tohru Ohe

    Circulation journal : official journal of the Japanese Circulation Society   68 ( 2 )   135 - 8   2004.2

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    BACKGROUND: It has been reported that recording electrocardiograms (ECGs) in the 3rd intercostal space (ICS) is one method that can be used for detecting Brugada syndrome; however, the prevalence of Brugada-type ECGs recorded in the 3rd ICS and the usefulness of recording the ECG in the 3rd ICS in accordance with recently established electrocardiographic criteria is unknown. METHODS AND RESULTS: ECGs were recorded in both the 4th and 3rd ICS in 17 Brugada-type ECG patients (group A) and in 206 consecutive male subjects (group B). Brugada-type ECGs were divided into 3 types. In group A, the prevalence of type 1 ECG, which is a coved-type ECG with ST-segment elevation of >/=2 mm, increased from 23.5% to 64.7% when ECG was recorded in the 3rd ICS. The conversion to type 1 ECG was found to be related to induction of ventricular arrhythmia. In group B, the prevalence of Brugada-type ECG increased from 1.5% to 5.8% when the ECG was recorded in the 3rd ICS. CONCLUSIONS: Recording the ECG in the 3rd ICS is useful for identifying high-risk patients with Brugada-type ECG and for detecting concealed Brugada-type ECG.

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  • Ventricular arrhythmia induced by sodium channel blocker in patients with Brugada syndrome. International journal

    Hiroshi Morita, Shiho Takenaka Morita, Satoshi Nagase, Kimikazu Banba, Nobuhiro Nishii, Yoshinori Tani, Atsuyuki Watanabe, Kazufumi Nakamura, Kengo Fukushima Kusano, Tetsuro Emori, Hiromi Matsubara, Kazumasa Hina, Toshimasa Kita, Tohru Ohe

    Journal of the American College of Cardiology   42 ( 9 )   1624 - 31   2003.11

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    OBJECTIVES: We administered pilsicainide chloride, a class Ic pure sodium channel blocker, to patients with Brugada syndrome (BS) and evaluated the occurrence of ventricular arrhythmia (VA) and T-wave alternans (TWA). BACKGROUND: Ventricular arrhythmia and TWA are sometimes induced by a sodium channel blocker challenge test in BS patients, but the significance of the induced VA and TWA is not known. METHODS: Pilsicainide was administered to 65 patients with BS (10 symptomatic and 55 asymptomatic patients), and the occurrence of VA, TWA, and change of electrocardiogram were evaluated. Electrophysiologic study was performed in 57 patients, and the induction of VA by programmed electrical stimulation (PES) was evaluated. RESULTS: Ventricular arrhythmia was not induced by administration of pilsicainide in 55 patients (no-VA group). Administration of pilsicainide-induced VA in 10 patients (Pil-VA group) and polymorphic ventricular tachycardia in four patients. Pilsicainide-induced VA in 60% of the symptomatic patients but in only 7% of asymptomatic patients (p < 0.01). ST level, QTc, and indexes of cardiac conduction in the Pil-VA group were not different from those in the no-VA group. Ventricular fibrillation was induced by PES in 67% of the patients in the Pil-VA group and in 33% of the patients in the no-VA group. In six cases, macroscopic TWA occurred in association with pilsicainide-induced VA, but TWA occurred in only one patient without pilsicainide-induced arrhythmia. CONCLUSIONS: Administration of a sodium channel blocker results in induction of not only ST-elevation but also VA and TWA in patients with BS.

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  • Site-specific arrhythmogenesis in patients with Brugada syndrome. International journal

    Hiroshi Morita, Kengo Fukushima-Kusano, Satoshi Nagase, Shiho Takenaka-Morita, Nobuhiro Nishii, Mikio Kakishita, Kazufumi Nakamura, Tetsuro Emori, Hiromi Matsubara, Tohru Ohe

    Journal of cardiovascular electrophysiology   14 ( 4 )   373 - 9   2003.4

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    INTRODUCTION: It has been believed that electrophysiologic abnormality of the epicardial region of the right ventricular free wall may play an important role in arrhythmogenesis of phase 2 reentry in Brugada syndrome, but clinical evidence of the occurrence of ventricular arrhythmias at the right ventricular free wall has not been evaluated. In this study, we evaluated the site-specific inducibility of ventricular fibrillation (VF) and the origin of spontaneous premature ventricular contractions (PVCs) in patients with Brugada syndrome. METHODS AND RESULTS: Forty-five patients with Brugada-type ECG were enrolled in this study. Spontaneous PVCs were recorded in 9 patients. Programmed electrical stimulation (PES) was performed at the right ventricular apex (RVA), the free wall and septal region of the right ventricular outflow tract (RVOT), and the left ventricle (LV). The inducibility of PVT/VF was evaluated at each ventricular site, and the origin of PVC was determined by pace mapping. Sustained VF was induced in 17 patients. VF was induced in all 17 patients by PES at RVOT. Although PES at the septal region of the RVOT induced VF in only 5 patients (29%), PES at the free-wall region of the RVOT induced PVT/VF in 13 patients (76%). PES at RVA induced VF in only 2 patients (12%), and PES at LV failed to induce any arrhythmic events. Ventricular pace mapping showed that 64% of PVCs occurred at the free-wall region of the RVOT, 18% at the septal region of the RVOT, 9% at RVA, and 9% at LV. CONCLUSION: VF in patients with Brugada syndrome frequently is induced at the free-wall region of the RVOT area. The origin of PVC appears to be related to the site of PVT/VF induction by PES.

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  • Risk stratification for asymptomatic patients with Brugada syndrome.

    Hiroshi Morita, Shiho Takenaka-Morita, Kengo Fukushima-Kusano, Makoto Kobayashi, Satoshi Nagase, Mikio Kakishita, Kazufumi Nakamura, Tetsuro Emori, Hiromi Matsubara, Tohru Ohe

    Circulation journal : official journal of the Japanese Circulation Society   67 ( 4 )   312 - 6   2003.4

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    Ventricular fibrillation (VF) is induced in some asymptomatic patients with Brugada syndrome (BS), but the prognostic value of programmed electrical stimulation (PES) in such patients is controversial. The clinical characteristics of 41 asymptomatic BS patients, divided into 2 groups according to whether VF was induced by PES (inducible VF group: n=13, non-inducible VF group: n=28) were evaluated. ST levels in the right precordial leads were measured before and after administration of pilsicainide and the abnormal late potential (LP) was evaluated on the signal-averaged electrogram. The ST level at V(2) at baseline in the inducible VF group was significantly higher than that in the non-inducible VF group (p<0.05). Pilsicainide induced significant ST segment elevation in both groups and the ST level after pilsicainide in the inducible VF group was higher than that in the non-inducible VF group (p<0.01). LP was more frequent in the inducible VF group than in the non-inducible VF group. The criterion of ST level >0.15 mV at baseline with pilsicainide-induced additional ST elevation >0.10 mV and positive LP showed high sensitivity (92%) and specificity (89%) for detection of PES-induced VF in asymptomatic BS patients.

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  • Atrial fibrillation and atrial vulnerability in patients with Brugada syndrome. International journal

    Hiroshi Morita, Kengo Kusano-Fukushima, Satoshi Nagase, Yoshihisa Fujimoto, Kenichi Hisamatsu, Hideki Fujio, Kayo Haraoka, Makoto Kobayashi, Shiho Takenaka Morita, Kazufumi Nakamura, Tetsuro Emori, Hiromi Matsubara, Kazumasa Hina, Toshimasa Kita, Masahiko Fukatani, Tohru Ohe

    Journal of the American College of Cardiology   40 ( 8 )   1437 - 44   2002.10

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    OBJECTIVES: We sought to study atrial vulnerability in patients with Brugada syndrome. BACKGROUND: Atrial fibrillation (AF) often occurs in patients with Brugada syndrome, but atrial vulnerability in Brugada syndrome has not been evaluated. METHODS: The patient group consisted of 18 patients with Brugada syndrome. The control group consisted of 12 age- and gender-matched subjects who had neither organic heart disease nor AF episodes. The incidence and clinical characteristics of AF were evaluated in all 18 patients with Brugada syndrome, and an electrophysiologic study was performed in all 12 control subjects and in 14 of the 18 patients with Brugada syndrome. The atrial effective refractory period of the right atrium (RA-ERP), intra-atrial conduction time (conduction time from the stimulus at the right atrium to atrial deflection at the distal portion of the coronary sinus), duration of local atrial potential, and repetitive atrial firing (occurrence of two or more premature atrial complexes after atrial stimulation) were studied. RESULTS: Spontaneous AF occurred in 7 of the 18 patients with Brugada syndrome but in none of the control subjects. The RA-ERP was not different between the two groups. The intra-atrial conduction time was increased in the Brugada syndrome group versus the control group (168.4 +/- 17.5 vs. 131.8 +/- 13.0 ms, p < 0.001). The duration of atrial potential at the RA-ERP was prolonged in the Brugada syndrome group versus the control group (80.3 +/- 18.0 vs. 59.3 +/- 9.2 ms, p < 0.001). Repetitive atrial firing was induced in nine patients with Brugada syndrome and in six control subjects. Atrial fibrillation was induced in eight patients with Brugada syndrome but in none of the control subjects. In patients with Brugada syndrome without spontaneous AF, the intra-atrial conduction time and duration of atrial potential were also increased. CONCLUSIONS: Atrial vulnerability is increased in patients with Brugada syndrome. Abnormal atrial conduction may be an electrophysiologic basis for induction of AF in patients with Brugada syndrome.

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  • Spontaneous T wave alternans and premature ventricular contractions during febrile illness in a patient with Brugada syndrome. International journal

    Hiroshi Morita, Satoshi Nagase, Kengo Kusano, Tohru Ohe

    Journal of cardiovascular electrophysiology   13 ( 8 )   816 - 8   2002.8

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    A 69-year-old man who had experienced syncope and ventricular fibrillation was referred to our hospital. ECG showed a right bundle branch block pattern with ST segment elevation in the right precordial leads. When the patient presented to the hospital with febrile illness, spontaneous T wave alternans and premature ventricular contractions were observed. When the patient became afebrile, ST segment elevation improved, and T wave alternans and premature ventricular contractions disappeared.

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  • [Advanced endocardial mapping systems].

    Hiroshi Morita, Yasuyuki Kouno, Tohru Ohe

    Nihon rinsho. Japanese journal of clinical medicine   60 ( 7 )   1334 - 40   2002.7

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    The technique of endocardial mapping was developed by the advancement of radiofrequency catheter ablation techniques. Because the catheter ablation has been performed various complex arrhythmias, simple-catheter based mapping methods was limited and multiple electrodes catheter mapping and computed mapping system were developed. The basket catheter has 64-unipolar electrodes and can records endocardial potential during arrhythmia for a moment. The electro-anatomical mapping system, CARTO system, can records entire circuit of arrhythmia and point the critical area, but it will expend more time for mapping and can not indicate for unstable arrhythmias. The new mapping systems, include noncontact mapping system and LocaLisa system, will be able to use in the near future in Japan.

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  • Epicardial electrogram of the right ventricular outflow tract in patients with the Brugada syndrome: using the epicardial lead. International journal

    Satoshi Nagase, Kengo Fukushima Kusano, Hiroshi Morita, Yoshihisa Fujimoto, Mikio Kakishita, Kazufumi Nakamura, Tetsuro Emori, Hiromi Matsubara, Tohru Ohe

    Journal of the American College of Cardiology   39 ( 12 )   1992 - 5   2002.6

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    OBJECTIVES: We tried to record an epicardial electrogram directly, and we examined local electrograms before and after administration of a class IC anti-arrhythmic drug in patients with the Brugada syndrome. BACKGROUND: Electrical heterogeneity of the epicardium in the right ventricular outflow tract (RVOT) has been thought to be related to the Brugada syndrome. However, an epicardial abnormality has not been demonstrated in patients with the Brugada syndrome. METHODS: In five patients with a Brugada-type electrocardiogram (ECG), local unipolar electrograms were recorded at the epicardium and endocardium of the RVOT. To record the epicardial electrogram directly, we introduced an electrical guidewire into the conus branch (CB) of the right coronary artery. The duration of the local electrogram after termination of the QRS complex (DP) was measured before and after class IC anti-arrhythmic drug administration. The signal-averaged electrocardiogram (SAECG) was also obtained in all patients. RESULTS: A definite DP was observed at the epicardium, but not at the endocardium. After administration of a class IC anti-arrhythmic drug, the DP at the epicardium was prolonged from 38 +/- 10 ms to 67 +/- 24 ms. The late potential corresponding to the DP at the epicardium was observed in all patients on the SAECG. CONCLUSIONS: An epicardial electrogram can be recorded from the CB. Recording from the CB enables identification of an epicardial abnormality in patients with the Brugada syndrome. These abnormal electrograms may be related to a myocardial abnormality in the epicardium of patients with the Brugada syndrome.

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  • Hepatitis C Infection in a Patient With Dermato - Myositis and Left Ventricular Dysfunction

    NAKAMURA Kazufumi, MATSUMORI Akira, KUSANO Kengo, BANDA Kimikazu, TANIYAMA Makiko, NAKAMURA Yoichi, MORITA Hiroshi, MATSUBARA Hiromi, YAMANARI Hiroshi, OHE Tohru

    Circulation Journal   64 ( 8 )   617 - 618   2000.7

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    Hepatitis C virus (HCV) infection is frequently associated with autoimmune disease. We present here a case of dermatomyositis manifested as heart failure in which HCV was detected from an endomyocardial biopsy sample. HCV infection may have contributed to the left ventricular dysfunction in this patient with dermatomyositis.

    DOI: 10.1253/jcj.64.617

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    Other Link: http://search.jamas.or.jp/link/ui/2000266900

  • Involvement of Ca^<2+> in Antiarrhythmic Effect of Ischemic Preconditioning in Isolated Rat Heart

    HONG Kui, FUKUSHIMA-KUSANO Kengo, MORITA Hiroshi, FUJIMOTO Yoshihisa, NAKAMURA Kazufumi, YAMANARI Hiroshi, OHE Tohru

    The Journal of Physiological Sciences   50 ( 2 )   207 - 213   2000.4

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    We investigated the relationship between the effects of ischemic preconditioning (IPC) and Ca2+ preconditioning (CPC) on reperfusion-induced arrhythmias. In the control group (noPC), Langendorff-perfused rat hearts were subjected to 5-min zero-flow global ischemia (I) followed by 15-min reperfusion (I/R). In ischemic preconditioning groups (IPC), the hearts were subjected to three cycles of 3-min global ischemia and 5-min reperfusion. In the CPC group, the hearts were exposed to three cycles of 3-min perfusion of higher Ca2+ (2.3 mmol/l Ca2+) followed by 5-min perfusion of normal 1.3 mmol/l Ca2+, and the hearts were then subjected to I/R. Verapamil was administered in several hearts of the IPC group (VR+IPC). Ventricular arrhythmias upon reperfusion were less frequently seen in the IPC and CPC groups than in the noPC and VR+IPC groups. IPC and CPC could attenuate conduction delay and enhance shortening of the monophasic action potential duration during ischemia. The ventricular fibrillation threshold measured at 1-min reperfusion was significantly higher in the IPC and CPC groups than in the noPC and VR+IPC groups. Verapamil completely abolished the salutary effects of IPC. These results demonstrate that Ca2+ plays an important role in the antiarrhythmic effect of IPC during reperfusion.<br>

    DOI: 10.2170/jjphysiol.50.207

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    Other Link: https://jlc.jst.go.jp/DN/JALC/00089129272?from=CiNii

  • Attenuation of conduction delay by ischemic preconditioning reduces ischemia-induced ventricular arrhythmias.

    Hong Kui, Kusano Kengo Fukushima, Morita Hiroshi, Fujimoto Yoshihisa, Wang Xian, Yamanari Hiroshi, Ohe Tohru

    Acta Medica Okayama   53 ( 5 )   233 - 238   1999.10

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    DOI: 10.18926/AMO/31636

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  • Evaluation of Autonomic Nervous Activity in Patients With Congenital Long QT Syndrome by an Analysis of RR Variability

    MORITA Hiroshi, YAMANARI Hiroshi, OHE Tohru

    Circulation Journal   60 ( 10 )   742 - 748   1996.9

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    Congenital long QT syndrome (LQTS) is a rare hereditary disease characterized by a prolonged QT interval and lethal ventricular tachycardia (Torsades de Pointes: TdP). The pathogenesis of LQTS and the induction of TdP have been thought to be closely related to autonomic nervous abnormalities. We examined autonomic activity in 13 LQTS patients by analyzing heart rate variability from 24 h Holter ambulatory electrocardiographic recordings without medications. In a frequency-analysis of RR variability, we calculated the power in the low-frequency domain (LF) and the high-frequency domain (HF) over 24 h. The ratio of LF to HF (an index of sympathetic nervous activity) was lower in LQTS patients than in controls, whereas HF (an index of parasympathetic nervous activity) was higher. Moreover, LQTS patients with TdP had lower abnormal sympathetic nervous activity than those without TdP. The index of autonomic nervous activity obtained using this method could be useful for evaluating the severity in LQTS. (Jpn Circ J 1996; 60: 742 - 748)

    DOI: 10.1253/jcj.60.742

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    Other Link: http://search.jamas.or.jp/link/ui/1997084639

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Books

  • Q&Aでわかる!糖尿病×循環器疾患の治療 : 血糖管理だけではない新しい考え方

    伊藤, 浩(内科医)(糖尿病と突然死の関連性は?)

    南江堂  2021.9  ( ISBN:9784524229581

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    Total pages:ix, 209p   Language:Japanese

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  • 臨床循環器学

    伊藤, 浩(内科医), 坂田, 泰史(失神と心臓突然死)

    文光堂  2021.3  ( ISBN:9784830619670

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    Total pages:xvi, 829p   Language:Japanese

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  • 一からわかる循環器腎臓病学 : CKD合併心血管疾患治療のノウハウ

    伊藤, 浩(内科医)( Role: Joint author ,  CKDと突然死.)

    文光堂  2021.3  ( ISBN:9784830619687

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    Total pages:iii, 169p   Language:Japanese

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  • 高齢者の循環器診療Q&A : 快適な人生を過ごしてもらう診療のツボ

    伊藤, 浩(内科医)( Role: Joint author ,  徐脈性不整脈とペースメーカ治療の適応について教えて下さい.)

    文光堂  2021.2  ( ISBN:9784830619663

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    Total pages:iii, 191p   Language:Japanese

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  • 心電図診断ドリル : 波形のここに注目!

    森田, 宏( Role: Edit)

    羊土社  2019.4  ( ISBN:9784758116244

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    Total pages:270p   Language:Japanese

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  • 血栓を制するものは心臓を制す!血栓循環器学Q&A : 抗凝固療法・抗血小板療法のクリニカルクエスチョンに答える

    伊藤, 浩(内科医)( Role: Joint author ,  DOAC時代になりAF患者の抗凝固療法の適応はどうなったのでしょうか?)

    文光堂  2019.3  ( ISBN:9784830619472

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    Total pages:vi, 156p   Language:Japanese

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  • 心臓を守る!ミネラルコルチコイド受容体拮抗薬 : MRAの実力をQ&Aで解き明かす

    伊藤, 浩(内科医)( Role: Joint author ,  MRAでしばしば高K血症が問題になりますが、心不全患者における適正な血清K値に関して教えて下さい。)

    文光堂  2019.3  ( ISBN:9784830619465

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    Total pages:140p   Language:Japanese

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  • 循環器内科グリーンノート

    伊藤, 浩(内科医)(心電図)

    中外医学社  2018.3  ( ISBN:9784498134270

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    Total pages:v, 542p   Language:Japanese

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  • 循環器内科グリーンノート

    伊藤, 浩(内科医)( Role: Joint author ,  抗不整脈薬の使い方)

    中外医学社  2018.3  ( ISBN:9784498134270

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    Total pages:v, 542p   Language:Japanese

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  • 循環器疾患最新の治療

    安田, 寿一, 杉本, 恒明, 篠山, 重威, 矢崎, 義雄, 堀, 正二, 永井, 良三, 伊藤, 浩(内科医), 山下, 武志( Role: Joint author ,  J波症候群(Brugada症候群、早期再分極症候群))

    南江堂  1986 

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    Total pages:冊   Language:Japanese

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MISC

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Awards

  • Best Poster Award

    2015.10   Asian Pacific Heart Rhythm Society  

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  • 医科学応用研究財団助成による日本心電学会論文賞

    2010.10   日本心電学会  

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  • 日本不整脈学会 メドトロニック・フェローシップ

    2008.5   日本不整脈学会  

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  • 砂田賞

    2002.9   岡山大学  

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  • 日本心電学会学術奨励賞

    2002.6   日本心電学会  

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Class subject in charge

  • Internal Medicine (2021academic year) 1st and 2nd semester  - [第1学期]月4,月5,水6, [第2学期]月4,月5,金6

  • Cardiovascular Medicine(Core Clinical Practice) (2021academic year) special  - その他

  • Research Projects and Practicals: Cardiovascular Medicine I (2021academic year) special  - その他

  • Lecture and Research Projects: Cardiovascular Medicine I (2021academic year) special  - その他

  • Research Projects and Practicals: Cardiovascular Medicine II (2021academic year) special  - その他

  • Lecture and Research Projects: Cardiovascular Medicine II (2021academic year) special  - その他

  • Cadiovascular Disease (2021academic year) special  - その他

  • Lecture: Myocardial Infarction (2021academic year) special  - その他

  • Internal Medicine (2020academic year) 1st and 2nd semester  - [第1学期]月4,月5,水6, [第2学期]月4,月5,金6

  • Cardiovascular Medicine(Core Clinical Practice) (2020academic year) special  - その他

  • Research Projects and Practicals: Cardiovascular Medicine I (2020academic year) special  - その他

  • Lecture and Research Projects: Cardiovascular Medicine I (2020academic year) special  - その他

  • Research Projects and Practicals: Cardiovascular Medicine II (2020academic year) special  - その他

  • Lecture and Research Projects: Cardiovascular Medicine II (2020academic year) special  - その他

  • Cadiovascular Disease (2020academic year) special  - その他

  • Social Medicine and Dentistry (2020academic year) Concentration  - その他

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