Faculty Profiles - MORITA Hiroshi

Papers - MORITA Hiroshi

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Impact of High-Sensitivity Cardiac Troponin T on Clinical Outcomes in Patients With Cardiac Sarcoidosis.

Yoichi Takaya, Koji Nakagawa, Toru Miyoshi, Nobuhiro Nishii, Hiroshi Morita, Kazufumi Nakamura, Shinsuke Yuasa

Circulation journal : official journal of the Japanese Circulation Society 2025.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The prognostic utility of high-sensitivity cardiac troponin T (hs-cTnT) on clinical outcomes in cardiac sarcoidosis (CS) remains unknown, so we evaluated hs-cTnT in the chronic phase of CS. METHODS AND RESULTS: We enrolled 92 consecutive patients with CS in the chronic phase after medical therapies. Patients were divided into 2 groups according to hs-cTnT level: 0.014 ng/mL: high hs-cTnT (n=37); normal hs-cTnT (n=55). The primary endpoint was cardiac death and the secondary endpoint was cardiac death, ventricular tachyarrhythmias, or hospitalization for heart failure. The mean age of patients was 63±11 years, and 75 received steroid treatment. During a median follow-up of 63 months, there were 9 cardiac deaths: 7 (19%) patients with high hs-cTnT and 2 (4%) patients with normal hs-cTnT. The rate of cardiac death was higher in patients with high hs-cTnT than in those with normal hs-cTnT (log-rank, P<0.01). Cox proportional hazard analysis showed that hs-cTnT was an independent predictor of cardiac death. The events rate was higher in patients with high hs-cTnT than in those with normal hs-cTnT (log-rank, P<0.01): cardiac death, ventricular tachyarrhythmias or hospitalization for heart failure occurred in 24 (65%) patients with high hs-cTnT and 11 (20%) patients with normal hs-cTnT. CONCLUSIONS: Elevated hs-cTnT was linked with adverse outcomes in CS patients, suggesting it is an effective prognostic biomarker.

DOI： 10.1253/circj.CJ-24-0801

Life-Threatening Ventricular Tachyarrhythmia in Isolated Cardiac Sarcoidosis Compared With Cardiac Sarcoidosis With Extracardiac Involvement

Yoichi Takaya, Koji Nakagawa, Toru Miyoshi, Nobuhiro Nishii, Hiroshi Morita, Kazufumi Nakamura, Shinsuke Yuasa

The American Journal of Cardiology 2024.12

Efficacy of Ivabradine in Preventing Inappropriate Shock due to Sinus Tachycardia in a Patient with Cardiac Sarcoidosis

Takuro Masuda, Kazufumi Nakamura, Nobuhiro Nishii, Saori Asada, Akira Ueoka, Masakazu Miyamoto, Koji Nakagawa, Yoichi Takaya, Hironobu Toda, Hiroshi Morita, Shinsuke Yuasa

International Heart Journal 65 ( 6 ) 1167 - 1171 2024.11

Differences in clinical significance of atrial tachyarrhythmias in idiopathic ventricular fibrillation vs Brugada syndrome: A multicenter study

Tomofumi Mizuno, Nobuhiro Nishii, Hiroshi Morita, Takuro Masuda, Akira Ueoka, Saori Asada, Yoshimasa Morimoto, Masakazu Miyamoto, Satoshi Kawada, Tadashi Wada, Shigeki Hiramatsu, Keisuke Okawa, Motoki Kubo, Koji Nakagawa, Atsuyuki Watanabe, Kazufumi Nakamura, Shinsuke Yuasa

Heart Rhythm O2 5 ( 11 ) 796 - 804 2024.11

Impact of extracardiac sarcoidosis on clinical outcomes in patients with cardiac sarcoidosis: Importance of continued screening for cardiac involvement. International journal

Yoichi Takaya, Koji Nakagawa, Toru Miyoshi, Nobuhiro Nishii, Hiroshi Morita, Kazufumi Nakamura, Shinsuke Yuasa

International journal of cardiology 413 132368 - 132368 2024.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The prognostic impact of extracardiac sarcoidosis remains unknown in cardiac sarcoidosis (CS). We aimed to evaluate the influence of extracardiac sarcoidosis on clinical outcomes and the effect of continued outpatient visits for screening of cardiac involvement. METHODS: Ninety-nine patients with CS were divided into two groups: patients with systemic CS who had prior extracardiac sarcoidosis, patients with isolated CS who had no prior extracardiac sarcoidosis. Patients with systemic CS were divided according to the continuation of outpatient visits. The endpoint was cardiac death, fatal ventricular arrhythmia, or hospitalization for heart failure. RESULTS: At the time of diagnosing CS, patients with isolated CS had a higher prevalence of high-grade atrioventricular block or fatal ventricular arrhythmia, and left ventricular contractile dysfunction than those with systemic CS. Over a median follow-up of 42 months, cardiac events occurred in 19 (37%) of 52 patients with systemic CS and in 27 (57%) of 47 patients with isolated CS. The event-free survival rate was worse in patients with isolated CS than in those with systemic CS. Cox proportional hazard analysis showed that the absence of prior extracardiac sarcoidosis was an independent predictor of adverse outcomes. Patients with systemic CS who ceased outpatient visits had a lower left ventricular ejection fraction with severe heart failure symptoms and a worse event-free survival rate than those who continued outpatient visits. CONCLUSIONS: The presence of extracardiac sarcoidosis is associated with clinical outcomes. The cessation of screening for cardiac involvement after diagnosing extracardiac sarcoidosis is associated with adverse outcomes.

DOI： 10.1016/j.ijcard.2024.132368

Late gadolinium enhancement in early repolarization syndrome

Hiroshi Morita, Saori Asada, Satoshi Nagase, Akira Ueoka, Takuro Masuda, Masakazu Miyamoto, Koji Nakagawa, Nobuhiro Nishii, Shinsuke Yuasa

Heart Rhythm 2024.7

Demonstration of Arrhythmia Substrate-Associated Dispersion of Repolarization by Epicardial Unipolar Mapping in Brugada Syndrome. International journal

Satoshi Nagase, Naoya Kataoka, Hiroshi Morita, Tsukasa Kamakura, Akira Ueoka, Toshihiro Nakamura, Satoshi Oka, Yuichiro Miyazaki, Akinori Wakamiya, Kenzaburo Nakajima, Nobuhiko Ueda, Mitsuru Wada, Kohei Ishibashi, Yuko Inoue, Koji Miyamoto, Takeshi Aiba, Kengo Kusano

JACC. Clinical electrophysiology 2024.5

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Epicardial unipolar mapping has not been thoroughly investigated in Brugada syndrome (BrS). OBJECTIVES: This study aims to examine the characteristics of epicardial unipolar potentials in BrS and investigate the differences from overt cardiomyopathy. METHODS: Epicardial mapping was performed in 8 patients with BrS and 6 patients with cardiomyopathy. We investigated the J-wave amplitudes using unipolar recordings at delayed potential (DP) sites via bipolar recordings. The repolarization time (RT) at and around the DP recording sites was measured, and maximum dispersion of the RT divided by the distance was defined as the RT dispersion index. RESULTS: Epicardial mapping at baseline revealed significantly higher J-wave amplitude with bipolar DP in patients with BrS than in patients with cardiomyopathy. J-wave amplitude ≥0.42 mV had 99.1% sensitivity and 100% specificity for diagnosing BrS. The RT dispersion index was significantly higher in patients with BrS than in patients with cardiomyopathy at baseline. In all patients with BrS, coved-type unipolar electrograms without negative T waves (short RT) appeared close to coved-type electrograms with negative T waves (long RT) at the DP recording sites after pilsicainide administration. Thus, a steep RT dispersion was observed in this region, and ventricular arrhythmias emerged from this shorter RT area in all 3 patients with BrS in whom ventricular arrhythmias were induced. CONCLUSIONS: Bipolar DP-related prominent unipolar J waves and steep repolarization gradients may be more specific for characterizing BrS than for overt cardiomyopathy. Ventricular arrhythmias in BrS are associated with a steep repolarization gradient, indicating phase 2 re-entry as a possible cause.

DOI： 10.1016/j.jacep.2024.05.012

Clinical characteristics of electrical storm in patients with early repolarization syndrome

Hiroshi Morita, Akira Ueoka, Tomofumi Mizuno, Takuro Masuda, Saori Asada, Kentaro Ejiri, Masakazu Miyamoto, Satoshi Kawada, Koji Nakagawa, Nobuhiro Nishii, Shinsuke Yuasa

Heart Rhythm 21 ( 5 ) 562 - 570 2024.5

Risk stratification for the occurrence of ventricular fibrillation in patients with early repolarization syndrome

Hiroshi Morita, Saori Asada, Akira Ueoka, Tomofumi Mizuno, Takuro Masuda, Masakazu Miyamoto, Satoshi Kawada, Koji Nakagawa, Nobuhiro Nishii, Shinsuke Yuasa

Heart Rhythm 2024.5

Artificial intelligence to detect noise events in remote monitoring data

Nobuhiro Nishii, Kensuke Baba, Ken'ichi Morooka, Haruto Shirae, Tomofumi Mizuno, Takuro Masuda, Akira Ueoka, Saori Asada, Masakazu Miyamoto, Kentaro Ejiri, Satoshi Kawada, Koji Nakagawa, Kazufumi Nakamura, Hiroshi Morita, Shinsuke Yuasa

Journal of Arrhythmia 2024.4

Publishing type：Research paper (scientific journal) Publisher：Wiley

Abstract

Background

Remote monitoring (RM) of cardiac implantable electrical devices (CIEDs) can detect various events early. However, the diagnostic ability of CIEDs has not been sufficient, especially for lead failure. The first notification of lead failure was almost noise events, which were detected as arrhythmia by the CIED. A human must analyze the intracardiac electrogram to accurately detect lead failure. However, the number of arrhythmic events is too large for human analysis. Artificial intelligence (AI) seems to be helpful in the early and accurate detection of lead failure before human analysis.

Objective

To test whether a neural network can be trained to precisely identify noise events in the intracardiac electrogram of RM data.

Methods

We analyzed 21 918 RM data consisting of 12 925 and 1884 Medtronic and Boston Scientific data, respectively. Among these, 153 and 52 Medtronic and Boston Scientific data, respectively, were diagnosed as noise events by human analysis. In Medtronic, 306 events, including 153 noise events and randomly selected 153 out of 12 692 nonnoise events, were analyzed in a five‐fold cross‐validation with a convolutional neural network. The Boston Scientific data were analyzed similarly.

Results

The precision rate, recall rate, F1 score, accuracy rate, and the area under the curve were 85.8 ± 4.0%, 91.6 ± 6.7%, 88.4 ± 2.0%, 88.0 ± 2.0%, and 0.958 ± 0.021 in Medtronic and 88.4 ± 12.8%, 81.0 ± 9.3%, 84.1 ± 8.3%, 84.2 ± 8.3% and 0.928 ± 0.041 in Boston Scientific. Five‐fold cross‐validation with a weighted loss function could increase the recall rate.

Conclusions

AI can accurately detect noise events. AI analysis may be helpful for detecting lead failure events early and accurately.

DOI： 10.1002/joa3.13037

心臓突然死;診断と予防・治療の最前線(Significant Delayed Conduction and Ventricular Tachycardia Morphologies are Associated with Electrical Strom in Patients with Cardiac Sarcoidosis)

森田宏, 中川晃志, 小倉聡一郎, 上岡亮, 水野智文, 増田拓郎, 浅田早央莉, 宮本真和, 川田哲史, 西井伸洋, 中村一文

日本循環器学会学術集会抄録集 88回 SY04 - 1 2024.3

Prevalence and Characteristics of Syncope and Loss of Consciousness Following Cardioverter-Defibrillator Implantation in Patients with Brugada Syndrome during Long-Term Follow-Up(タイトル和訳中)

浅田早央莉, 森田宏, 水野智文, 増田拓郎, 上岡亮, 宮本真和, 中川晃志, 西井伸洋, 中村一文

日本循環器学会学術集会抄録集 88回 OJ21 - 9 2024.3

The Usefulness of Stellate Ganglion Phototherapy for Electrical Storm of Ventricular Tachycardias(タイトル和訳中)

宮本真和, 森田宏, 山口聡美, 吉田優, 水野智文, 増田拓郎, 上岡亮, 浅田早央莉, 川田哲史, 中川晃志, 西井伸洋, 中村一文

日本循環器学会学術集会抄録集 88回 OJ01 - 3 2024.3

Effect of Tafamidis on Serum Transthyretin Levels in Patients with Transthyretin Amyloidosis Cardiomyopathy(タイトル和訳中)

森淳史, 中村一文, 斎藤幸弘, 吉田賢司, 谷山真規子, 三好亨, 森田宏, 赤木禎治, 西井伸洋, 中川晃志

日本循環器学会学術集会抄録集 88回 PJ065 - 2 2024.3

Local dispersion of repolarization in the occurrence of ventricular fibrillation in Brugada syndrome: Possibility of phase 2 reentry? International journal

Satoshi Nagase, Satoshi Oka, Tsukasa Kamakura, Takeshi Aiba, Hiroshi Morita, Kengo Kusano

Pacing and clinical electrophysiology : PACE 2024.1

Language：English

To date, there have been no reports of recording epicardial electrograms at the onset of spontaneous ventricular fibrillation (VF) in patients with Brugada syndrome (BrS). In the case of BrS, unipolar and bipolar electrogram recording on the right ventricular epicardium revealed that dispersion of repolarization with delayed potential was associated with spontaneous occurrence of VF. Phase 2 reentry associated with shortening and dispersion of action potential could have been recorded for the first time in BrS. Epicardial unipolar mapping can guide accurate and appropriate ablation for the elimination of arrhythmia substrate in J wave syndrome.

DOI： 10.1111/pace.14917

Significant delayed conduction and characteristic ventricular tachycardias in patients with cardiac sarcoidosis and electrical storm. International journal

Hiroshi Morita, Koji Nakagawa, Akira Ueoka, Tomofumi Mizuno, Takuro Masuda, Saori Asada, Masakazu Miyamoto, Satoshi Kawada, Nobuhiro Nishii, Kazufumi Nakamura

Journal of cardiovascular electrophysiology 2023.12

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Electrical storm (ES) of ventricular tachyarrhythmias (VTAs) is an important cause of sudden death in patients with cardiac sarcoidosis (CS). VTAs in CS are associated with myocardial scarring and inflammation. However, little is known about the risk factors of ES in patients with CS and VTAs. The objective of this study is to clarify the characteristics and risk factors for the development of ES in patients with CS. METHODS: The study population included consecutive 52 patients with CS and sustained VTA. Twenty-five out of 52 patients experienced ES. We evaluated clinical characteristics, imaging modalities, and electrocardiogram (ECG) parameters to determine the risk factors associated with ES. RESULTS: Half of the patients experienced VTAs as the initial symptom of sarcoidosis, and eight patients had ES as the initial VTA episode. There were no differences in cardiac imaging abnormalities between patients with and without ES. Among ECG markers, significant QRS fragmentation (odds ratio [OR]: 7.9, p = .01) and epsilon waves (OR: 12.24, p = .02) were associated with ES. Among the ventricular tachycardia (VT) characteristics, multiple morphologies of monomorphic VTs (OR: 10.9, p < .01), short VT cycle lengths (OR: 12.5, p < .01), and polymorphic VT (OR: 13.5, p < .01) were associated with ES. Bidirectional VTs were detected in 10 patients with ES and one patient without ES. Immunosuppressive therapy relieved ES in some patients. CONCLUSIONS: ES was common in patients with CS and VTAs. Significant depolarization abnormalities that appeared as QRS fragmentation, epsilon waves, and specific VT characteristics were associated with ES.

DOI： 10.1111/jce.16156

A variability of the QRS morphology during wide QRS tachycardia. International journal

Saori Asada, Koji Nakagawa, Nobuhiro Nishii, Hiroshi Morita, Kazufumi Nakamura

Pacing and clinical electrophysiology : PACE 46 ( 12 ) 1568 - 1571 2023.12

Management of sensing issues with a subcutaneous implantable cardioverter-defibrillator in a patient with Brugada syndrome: A case report. International journal

Satoshi Kawada, Nobuhiro Nishii, Tomofumi Mizuno, Masakazu Miyamoto, Koji Nakagawa, Hiroshi Morita

HeartRhythm case reports 9 ( 12 ) 878 - 882 2023.12

Syncope and loss of consciousness after implantation of a cardioverter-defibrillator in patients with Brugada syndrome: Prevalence and characteristics in long-term follow-up. International journal

Saori Asada, Hiroshi Morita, Tomofumi Mizuno, Takuro Masuda, Akira Ueoka, Masakazu Miyamoto, Satoshi Kawada, Koji Nakagawa, Nobuhiro Nishii

Heart rhythm O2 4 ( 10 ) 641 - 649 2023.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Syncope is a significant prognostic factor in patients with Brugada syndrome (BrS). However, the risk of ventricular arrhythmia in patients with nonarrhythmic loss of consciousness (LOC) is similar to that in asymptomatic patients. LOC events after implantable cardioverter-defibrillator (ICD) implantation may provide insights into underlying causes of the initial LOC episode. OBJECTIVE: The purpose of this study was to examine LOC characteristics following ICD implantation. METHODS: We retrospectively analyzed 112 patients with BrS (mean age 47 years; 111 men) who were treated with an ICD. The patients were classified into 3 groups based on symptoms at implantation: asymptomatic (35 patients); LOC (46 patients); and ventricular tachyarrhythmia (VTA) (31 patients). We evaluated the incidence and cause of LOC during long-term follow-up after ICD implantation. RESULTS: During mean follow-up of 12.2 years, 41 patients (37%) experienced LOC after ICD implantation. Arrhythmic LOC occurred in 5 asymptomatic patients, 14 LOC patients, and 16 patients with VTA. Nonarrhythmic LOC, similar to the initial episode, occurred after ICD implantation in 6 patients with prior LOC (2 with neurally mediated syncope and 4 with epilepsy). Most epileptic patients experienced LOC during rest or sleeping, and did not show an abnormal encephalogram during initial evaluation of the LOC episodes. CONCLUSION: After ICD implantation, 13% of patients had nonarrhythmic LOC similar to the initial episode. Accurate classification of LOC based on a detailed medical history is important for risk stratification, although distinguishing arrhythmic LOC from epilepsy-related LOC episodes can be challenging depending on the circumstances and characteristics of the LOC event.

DOI： 10.1016/j.hroo.2023.09.007

非動脈硬化性末梢血管疾患の診断と治療 Radiation-induced arteriopathyと考えられた症例に対して、医原性尿管腸骨動脈瘻を生じた1例

戸田洋伸, 吉田雅言, 中川晃志, 三好亨, 西井伸洋, 中村一文, 森田宏

脈管学 63 ( Suppl. ) S141 - S141 2023.10

エキスパートコンセンサスステートメント心電図自動診断の精度評価ならびに有用性向上へのアプローチ(第3報) 自動診断過程における不適切自動処理の実態とその問題点

加藤貴雄, 渡邉英一, 八島正明, 高橋尚彦, 池田隆徳, 笠巻祐二, 住友直方, 植田典浩, 森田宏, 平岡昌和, 心電図自動診断を考える会

心電図 43 ( 3 ) 187 - 197 2023.10

Ventricular arrhythmias induced by phase 2 reentry in a patient with J-wave syndrome. International journal

Satoshi Kawada, Hiroshi Morita, Masakazu Miyamoto, Saori Asada, Koji Nakagawa, Nobuhiro Nishii

HeartRhythm case reports 9 ( 9 ) 629 - 633 2023.9

Significance of left posterior extension of early repolarization in patients with J-wave syndrome. International journal

Masakazu Miyamoto, Hiroshi Morita, Tomofumi Mizuno, Takuro Masuda, Akira Ueoka, Saori Asada, Satoshi Kawada, Koji Nakagawa, Nobuhiro Nishii

Heart rhythm 2023.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: J waves in the inferior or lateral leads are characteristic electrocardiographic (ECG) changes in patients with early repolarization syndrome (ERS). However, the presence of J waves in the left posterior region has not yet been evaluated. OBJECTIVE: The purpose of this study was to clarify the significance of J waves in the posterior left ventricle using leads V7-V9 and a body surface mapping (BSM) system. METHODS: Forty patients diagnosed with ERS were included. All patients exhibited J waves in either the contiguous inferior, lateral, or posterior leads. We evaluated the incidence of J waves in the inferolateral and posterior leads using a 15-lead ECG with synthesized V7-V9 and an 87-lead BSM. Additionally, we assessed the arrhythmogenicity of the posterior regions based on the morphology of the premature ventricular complexes (PVCs) associated with ventricular fibrillation (VF). RESULTS: J waves were observed in the lateral, inferior, and posterior leads of 26 (65%), 31 (78%), and 39 (97%) patients, respectively. J waves were found only in the posterior leads of 5 patients. BSM was evaluated in 9 patients, all of whom exhibited a positive area on the posterior region. PVCs associated with VF were recorded in 5 patients. Among patients with inferolateral and posterior J waves, all except 1 patient who displayed left bundle branch block morphology showed PVCs originating from the posterior left ventricular region. CONCLUSION: Posterior J waves are common in ERS patients. This abnormality can be detected using leads V7-V9 and the BSM system and may be associated with arrhythmogenesis.

DOI： 10.1016/j.hrthm.2023.08.032

Prevalence and Treatment of Arrhythmias in Patients With Transthyretin and Light-Chain Cardiac Amyloidosis.

Masakazu Miyamoto, Kazufumi Nakamura, Koji Nakagawa, Nobuhiro Nishii, Satoshi Kawada, Akira Ueoka, Saori Asada, Atsuyuki Watanabe, Hiroshi Morita, Hiroshi Ito

Circulation reports 5 ( 7 ) 298 - 305 2023.7

Language：English Publishing type：Research paper (scientific journal)

Background: Various types of arrhythmia are observed in patients with cardiac amyloidosis, but the prevalence of arrhythmia has not been fully investigated. This study investigated the prevalence and treatment of arrhythmias in patients with cardiac amyloidosis before the introduction of new agents for amyloidosis, such as tafamidis. Methods and Results: Of 53 patients who were histologically diagnosed with cardiac amyloidosis at 10 centers in western Japan between 2009 and 2021, 43 who were diagnosed on the basis of immunohistochemical staining were evaluated in this study. Of these 43 patients, 13 had immunoglobulin light-chain (AL) amyloidosis and 30 had transthyretin (ATTR) amyloidosis; further, 27 had atrial tachyarrhythmia, 13 had ventricular tachyarrhythmia, and 17 had bradyarrhythmia. Atrial fibrillation (AF) was the most common arrhythmia in patients with cardiac amyloidosis (n=24; 55.8%), especially among those with ATTR amyloidosis (70.0% of ATTR vs. 23.1% of AL). Eleven (25.6%) patients were treated with a cardiac implantable device. All 3 patients with pacemakers were alive at the last follow-up (median 76.7 months; interquartile range [IQR] 4.8-146.4 months). Of the 8 patients who underwent AF ablation, there was no recurrence in 6 (75%) after a median of 39.3 months (IQR 19.8-59.3 months). Conclusions: The prevalence of various arrhythmias was high in patients with cardiac amyloidosis. AF occurred most frequently in patients with cardiac amyloidosis, especially among patients with ATTR.

DOI： 10.1253/circrep.CR-23-0022

Effects of Agalsidase Alfa Enzyme Replacement Therapy on Left Ventricular Hypertrophy on Electrocardiogram in a Female Patient with Fabry Disease

Kazufumi Nakamura, Hiroshi Morita, Yoichi Takaya, Yukihiro Saito, Toru Miyoshi, Hiroshi Morinaga, Hitoshi Sugiyama, Jun Wada, Hiroshi Ito

International Heart Journal 64 ( 3 ) 502 - 505 2023.5

Significant Delayed Activation on the Right Ventricular Outflow Tract Represents Complete Right Bundle-Branch Block Pattern in Brugada Syndrome. International journal

Yoshimasa Morimoto, Hiroshi Morita, Kentaro Ejiri, Tomofumi Mizuno, Takuro Masuda, Akira Ueoka, Saori Asada, Masakazu Miyamoto, Satoshi Kawada, Koji Nakagawa, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Ito

Journal of the American Heart Association 12 ( 10 ) e028706 2023.5

Language：English Publishing type：Research paper (scientific journal)

Background The appearance of complete right bundle-branch block (CRBBB) in Brugada syndrome (BrS) is associated with an increased risk of ventricular fibrillation. The pathophysiological mechanism of CRBBB in patients with BrS has not been well established. We aimed to clarify the significance of a conduction delay zone associated with arrhythmias on CRBBB using body surface mapping in patients with BrS. Methods and Results Body surface mapping was recorded in 11 patients with BrS and 8 control patients both with CRBBB. CRBBB in control patients was transiently exhibited by unintentional catheter manipulation (proximal RBBB). Ventricular activation time maps were constructed for both of the groups. We divided the anterior chest into 4 areas (inferolateral right ventricle [RV], RV outflow tract [RVOT], intraventricular septum, and left ventricle) and compared activation patterns between the 2 groups. Excitation propagated to the RV from the left ventricle through the intraventricular septum with activation delay in the entire RV in the control group (proximal RBBB pattern). In 7 patients with BrS, excitation propagated from the inferolateral RV to the RVOT with significant regional activation delay. The remaining 4 patients with BrS showed a proximal RBBB pattern with the RVOT activation delay. The ventricular activation time in the inferolateral RV was significantly shorter in patients with BrS without a proximal RBBB pattern than in control patients. Conclusions The CRBBB morphology in patients with BrS consisted of 2 mechanisms: (1) significantly delayed conduction in the RVOT and (2) proximal RBBB with RVOT conduction delay. Significant RVOT conduction delay without proximal RBBB resulted in CRBBB morphology in patients with BrS.

DOI： 10.1161/JAHA.122.028706

肥大型心筋症患者における心房細動に対するカテーテルアブレーション後の抗不整脈薬併用療法の有効性(Efficacy of Adjunctive Antiarrhythmic Drug Therapy after Catheter Ablation for Atrial Fibrillation in Patients with Hypertrophic Cardiomyopathy)

宮本真和, 中川晃志, 水野智文, 増田拓郎, 上岡亮, 浅田早央莉, 川田哲史, 西井伸洋, 中村一文, 森田宏, 伊藤浩

日本循環器学会学術集会抄録集 87回 PJ003 - 1 2023.3

早期再分極症候群患者における左心室後外側の不整脈誘発性の意義(Significances of Arrhythmogenicity in Posterolateral Left Ventricle in Patients with Early Repolarization Syndrome)

宮本真和, 森田宏, 水野智文, 増田拓郎, 上岡亮, 浅田早央莉, 川田哲史, 中川晃志, 西井伸洋, 中村一文, 伊藤浩

日本循環器学会学術集会抄録集 87回 OJ29 - 3 2023.3

Temporary balloon occlusion test can overestimate the risk of acute pulmonary edema after transcatheter atrial septal defect closure. International journal

Koji Nakagawa, Teiji Akagi, Yoichi Takaya, Takashi Miki, Yasufumi Kijima, Rie Nakayama, Norihisa Toh, Nobuhiro Nishii, Kazufumi Nakamura, Hiroshi Morita, Hiroshi Ito

Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions 2023.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Atrial septal defect (ASD) closure can cause acute pulmonary edema. Before transcatheter closure is performed, temporary balloon occlusion test (BOT) is recommended in patients with left ventricular dysfunction to predict the risk of pulmonary edema. However, the accuracy of BOT has not been verified. This study aimed to compare hemodynamic differences between BOT and transcatheter closure. METHODS: A total of 42 patients with a single ASD over age 18 years who underwent BOT before transcatheter ASD closure between October 2010 and May 2020 were analyzed. Pulmonary capillary wedge pressure (PCWP) was measured using a Swan-Ganz catheter placed in the pulmonary artery at baseline, after 10 min of BOT, and after transcatheter closure. Amplatzer septal occluder was used for all transcatheter closures. RESULTS: Mean patient age was 64 ± 18 years (range, 18-78). Mean ASD diameter and pulmonary to systemic flow ratio were 18 ± 5 and 2.8 ± 1.0 mm, respectively. Mean PCWP at baseline, during BOT, and after transcatheter closure was 8.9 ± 2.9, 13.5 ± 4.2, and 9.5 ± 2.6 mmHg, respectively. The difference between BOT and after transcatheter closure values was significant (p < 0.001). During BOT, PCWP increased ≥18 mmHg in 7 patients, whereas after ASD closure, PCWP was <18 mmHg in all 7 and none developed acute pulmonary edema. CONCLUSION: Temporary balloon occlusion of an ASD and transcatheter ASD closure result in different hemodynamic change. BOT overestimates increase of PCWP after transcatheter ASD closure and requires careful interpretation. Well-designed, larger studies in higher-risk patients are warranted to verify the clinical implications of BOT in more detail.

DOI： 10.1002/ccd.30556

修復術後ファロー四徴症・類縁疾患の遠隔期肺動脈弁置換術における右室拡張障害の意義

中島充貴, 杜徳尚, 小谷恭弘, 川田哲史, 高谷陽一, 中川晃志, 西井伸洋, 中村一文, 森田宏, 赤木禎治, 笠原真悟, 伊藤浩

日本成人先天性心疾患学会雑誌 12 ( 1 ) 149 - 149 2023.1

心外膜心房リードのPacing failureに対し、鼠径部より経静脈ペースメーカを植え込んだGlenn手術後の一例

水野智文, 西井伸洋, 増田拓郎, 上岡亮, 浅田早央莉, 宮本真和, 川田哲史, 杜徳尚, 中川晃志, 森田宏, 赤木禎治, 伊藤浩, 笠原真悟

日本成人先天性心疾患学会雑誌 12 ( 1 ) 196 - 196 2023.1

Targeted deep sequencing analyses of long QT syndrome in a Japanese population. Reviewed International journal

Yuki Nagata, Ryo Watanabe, Christian Eichhorn, Seiko Ohno, Takeshi Aiba, Taisuke Ishikawa, Yukiko Nakano, Yoshiyasu Aizawa, Kenshi Hayashi, Nobuyuki Murakoshi, Tadashi Nakajima, Nobue Yagihara, Hiroyuki Mishima, Takeaki Sudo, Chihiro Higuchi, Atsushi Takahashi, Akihiro Sekine, Takeru Makiyama, Yoshihiro Tanaka, Atsuyuki Watanabe, Motomi Tachibana, Hiroshi Morita, Koh-Ichiro Yoshiura, Tatsuhiko Tsunoda, Hiroshi Watanabe, Masahiko Kurabayashi, Akihiko Nogami, Yasuki Kihara, Minoru Horie, Wataru Shimizu, Naomasa Makita, Toshihiro Tanaka

PloS one 17 ( 12 ) e0277242 2022.12

Language：English Publishing type：Research paper (scientific journal)

Long QT syndrome (LQTS) is one of the most common inherited arrhythmias and multiple genes have been reported as causative. Presently, genetic diagnosis for LQTS patients is becoming widespread and contributing to implementation of therapies. However, causative genetic mutations cannot be detected in about 20% of patients. To elucidate additional genetic mutations in LQTS, we performed deep-sequencing of previously reported 15 causative and 85 candidate genes for this disorder in 556 Japanese LQTS patients. We performed in-silico filtering of the sequencing data and found 48 novel variants in 33 genes of 53 cases. These variants were predicted to be damaging to coding proteins or to alter the binding affinity of several transcription factors. Notably, we found that most of the LQTS-related variants in the RYR2 gene were in the large cytoplasmic domain of the N-terminus side. They might be useful for screening of LQTS patients who had no known genetic factors. In addition, when the mechanisms of these variants in the development of LQTS are revealed, it will be useful for early diagnosis, risk stratification, and selection of treatment.

DOI： 10.1371/journal.pone.0277242

肝腎症候群急性期に冠攣縮によるST上昇型急性下壁心筋梗塞を合併し,集学的治療により救命し得た1例

長田栞, 中島充貴, 戸田洋伸, 平井亮佑, 高木章乃夫, 三木崇史, 赤木達, 吉田賢司, 中村一文, 赤木禎治, 森田宏, 伊藤浩

心臓 54 ( 10 ) 1164 - 1169 2022.10

Language：Japanese Publisher：(公財)日本心臓財団

43歳男性.非代償性アルコール性肝硬変のため他院で通院加療を行われていた.特発性細菌性腹膜炎を契機とした肝腎症候群による急性腎障害を発症し当院転院となった.著明なアシドーシスおよび腎不全を認め集中治療室に入室した.入院後,下壁誘導ST上昇および高度房室ブロックを生じショック状態に至った.気管挿管を行いアルブミン補充および昇圧薬を使用して呼吸循環を維持し,持続的血液濾過透析を施行しながら緊急冠動脈造影検査を施行した.右冠動脈中間部90%狭窄,左冠動脈前下行枝近位部90%狭窄,左冠動脈回旋枝中間部90%狭窄を認めたが,血管拡張薬冠注により狭窄は解除され冠攣縮に伴うST上昇型急性下壁心筋梗塞と診断した.ニコランジル持続静脈投与を開始しST変化や房室ブロックの再発を認めなかった.血行動態安定し,全身状態も改善に向かった.肝腎症候群は末期肝硬変に続発する腎皮質血管の攣縮により生じるとされ,肝・腎以外の臓器にも血流障害が併存する可能性を示唆されている.今回我々は肝腎症候群に冠攣縮による急性心筋梗塞を発症し,集学的治療により救命し得た1例を経験したためここに報告する.(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00679&link_issn=&doc_id=20221018180015&doc_link_id=%2Fah2sinzd%2F2022%2F005410%2F019%2F1164-1169%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fah2sinzd%2F2022%2F005410%2F019%2F1164-1169%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Overview of the 86th Annual Scientific Meeting of the Japanese Circulation Society - Cardiology Spreading Its Wings.

Kazufumi Nakamura, Toru Miyoshi, Satoshi Akagi, Norihisa Toh, Yukihiro Saito, Yoichi Takaya, Masatoki Yoshida, Koji Nakagawa, Satoshi Kawada, Hironobu Toda, Takashi Miki, Rie Nakayama, Fumi Yokohama, Keishi Ichikawa, Masashi Yoshida, Makiko Taniyama, Nobuhiro Nishii, Teiji Akagi, Hiroshi Morita, Hiroshi Ito

Circulation journal : official journal of the Japanese Circulation Society 86 ( 8 ) 1312 - 1318 2022.7

Language：English Publishing type：Research paper (scientific journal)

The 86thAnnual Scientific Meeting of the Japanese Circulation Society was held in a web-based format on March 11-13, 2022. In accordance with the internationalization policy of the JCS, the meeting was held with the Asian Pacific Society of Cardiology Congress 2022. The main theme was "Cardiology Spreading its Wings". The number of patients with heart failure and other cardiovascular diseases is increasing dramatically, and the fields dealt with by cardiovascular medicine are also greatly expanding. This conference was both intellectually satisfying and exciting for all participants, who numbered over 14,900. The meeting was completed with great success, and the enormous amount of cooperation and support from all involved was greatly appreciated.

DOI： 10.1253/circj.CJ-22-0349

Intermittent orthodromic capture of the earliest activation site during atrial pacing in a case with reentrant atrial tachycardia originating from the atrioventricular node vicinity.

Akira Ueoka, Satoshi Nagase, Koji Nakagawa, Hiroshi Morita, Hiroshi Ito

Journal of arrhythmia 38 ( 3 ) 473 - 477 2022.6

Language：English Publishing type：Research paper (scientific journal)

Constant pacing (S1-S1: 520 ms) from the right atrial appendage (RAA) during reentrant atrial tachycardia originating from the atrioventricular node vicinity. RA-FW 1-2 was constantly captured antidromically. However, the earliest atrial activation site (EAAS = His1-2) was orthodromically (red circle) and antidromically (blue square) captured at a ratio of 3:1. The electrogram morphology at the EAAS was different between orthodromically and antidromically electrograms captured during pacing. Moreover, the interval between the S1 and orthodromically captured electrogram was gradually prolonged.

DOI： 10.1002/joa3.12702

Impact of shear wave dispersion slope analysis for assessing the severity of myocarditis. International journal

Naofumi Amioka, Yoichi Takaya, Kazufumi Nakamura, Megumi Kondo, Kaoru Akazawa, Yuko Ohno, Keishi Ichikawa, Rie Nakayama, Yukihiro Saito, Satoshi Akagi, Toru Miyoshi, Masashi Yoshida, Hiroshi Morita, Hiroshi Ito

Scientific reports 12 ( 1 ) 8776 - 8776 2022.5

Language：English Publishing type：Research paper (scientific journal)

This study aimed to elucidate the utility of a novel ultrasound-based technique, shear wave dispersion slope (SWDS) analysis, which estimates tissue viscosity, for evaluating the severity of myocardial inflammation. Experimental autoimmune myocarditis (EAM) at different disease phases [3-week (acute phase): n = 10, 5-week (subacute phase): n = 9, and 7-week (late phase): n = 11] were developed in male Lewis rats. SWDS was measured in the right and the left ventricular free walls (RVFW and LVFW) under a retrograde perfusion condition. Histological myocardial inflammation was evaluated by CD68 staining. The accumulation of CD68-positive cells was severe in the myocardium of the EAM 3-week group. The median (interquartile range) SWDS of RVFW was significantly higher in the EAM 3-week group [9.9 (6.5-11.0) m/s/kHz] than in the control group [5.4 (4.5-6.8) m/s/kHz] (P = 0.034). The median SWDS of LVFW was also significantly higher in the EAM 3-week group [8.1 (6.4-11.0) m/s/kHz] than in the control group [4.4 (4.2-4.8) m/s/kHz] (P = 0.003). SWDS and the percentage of CD68-positive area showed a significant correlation in RVFW (R2 = 0.64, P < 0.001) and LVFW (R2 = 0.73, P < 0.001). This study showed that SWDS was elevated in ventricular walls with acute inflammation and also significantly correlated with the degree of myocardial inflammation. These results suggest the potential of SWDS in estimating the histological severity of acute myocarditis.

DOI： 10.1038/s41598-022-12935-6

Enhancement of pacing function by HCN4 overexpression in human pluripotent stem cell-derived cardiomyocytes. International journal

Yukihiro Saito, Kazufumi Nakamura, Masashi Yoshida, Hiroki Sugiyama, Satoshi Akagi, Toru Miyoshi, Hiroshi Morita, Hiroshi Ito

Stem cell research & therapy 13 ( 1 ) 141 - 141 2022.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The number of patients with bradyarrhythmia and the number of patients with cardiac pacemakers are increasing with the aging population and the increase in the number of patients with heart diseases. Some patients in whom a cardiac pacemaker has been implanted experience problems such as pacemaker infection and inconvenience due to electromagnetic interference. We have reported that overexpression of HCN channels producing a pacemaker current in mouse embryonic stem cell-derived cardiomyocytes showed enhanced pacing function in vitro and in vivo. The aim of this study was to determine whether HCN4 overexpression in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can strengthen the pacing function of the cells. METHODS: Human HCN4 was transduced in the AAVS1 locus of human induced pluripotent stem cells by nucleofection and HCN4-overexpressing iPSC-CMs were generated. Gene expression profiles, frequencies of spontaneous contraction and pacing abilities of HCN4-overexpressing and non-overexpressing iPSC-CMs in vitro were compared. RESULTS: HCN4-overexpressing iPSC-CMs showed higher spontaneous contraction rates than those of non-overexpressing iPSC-CMs. They responded to an HCN channel blocker and β adrenergic stimulation. The pacing rates against parent iPSC line-derived cardiomyocytes were also higher in HCN4-overexpressing iPSC-CMs than in non-overexpressing iPSC-CMs. CONCLUSIONS: Overexpression of HCN4 showed enhancement of If current, spontaneous firing and pacing function in iPSC-CMs. These data suggest this transgenic cell line may be useful as a cardiac pacemaker.

DOI： 10.1186/s13287-022-02818-y

Ablation for unmappable ventricular tachycardia in a patient with complete transposition of the great arteries who underwent Rastelli repair.

Takashi Nishimoto, Nobuhiro Nishii, Saori Asada, Koji Nakagawa, Hiroshi Morita, Hiroshi Ito

Journal of cardiology cases 25 ( 4 ) 218 - 224 2022.4

Language：English

Catheter ablation (CA) of ventricular tachycardia (VT) after repair of congenital heart disease may be difficult because of complex anatomy and sometimes unmappable VT. Here, we report a 41-year-old woman with successful CA of unmappable VT in a patient with complete transposition of the great arteries after Rastelli repair. Clinical VT was induced by programmed electrical stimulation, when the mapping catheter was placed at the high anterior right ventricular outflow tract (RVOT). During VT, the local potential at the high anterior RVOT under the right ventricle (RV) - pulmonary artery (PA) conduit was equal to that at the timing of onset of QRS. The VT was unmappable because the hemodynamics deteriorated. Pace mapping was also tried at the aortic cusp and the left ventricular outflow tract (LVOT). Fractionated potential during sinus rhythm was observed at the noncoronary cusp, and the paced QRS morphology at this site was similar to that of the clinical VT, with a delay of 55 ms from pacing to the onset of QRS. However, mapping at the LVOT was impossible due to the difficulty of catheter manipulation. Radiofrequency energy was successfully applied at the noncoronary cusp and the high anterior RVOT under the RV-PA conduit. <Learning objective: This report is a rare case of successful catheter ablation of unmappable ventricular tachycardia (VT) in a patient with complete transposition of the great arteries after Rastelli repair. The VT was unmappable because of intolerable hemodynamics. However, we could speculate the exit or isthmus of the VT by pace mapping or local potential and eliminate the VT.>.

DOI： 10.1016/j.jccase.2021.09.012

2型糖尿病患者におけるCTを用いた冠動脈周囲脂肪の炎症イメージングによるリスク評価

市川啓之, 三好亨, 中島充貴, 西原大裕, 三木崇史, 中村一文, 森田宏, 伊藤浩

日本内科学会雑誌 111 ( 臨増 ) 158 - 158 2022.2

心内短絡疾患における経静脈心内膜リードデバイスによる体塞栓イベントへの影響

中島充貴, 杜徳尚, 西井伸洋, 高谷陽一, 川田哲史, 中川晃志, 森田宏, 赤木禎治, 伊藤浩

日本成人先天性心疾患学会雑誌 11 ( 1 ) 197 - 197 2022.1

Expert consensus document on automated diagnosis of the electrocardiogram: The task force on automated diagnosis of the electrocardiogram in Japan: Part 2: Current status of inappropriate automated diagnosis is widely used electrocardiographs in Japan.

Takao Katoh, Masaaki Yashima, Naohiko Takahashi, Eiichi Watanabe, Takanori Ikeda, Yuji Kasamaki, Naokata Sumitomo, Norihiro Ueda, Hiroshi Morita, Masayasu Hiraoka

Journal of arrhythmia 37 ( 6 ) 1427 - 1433 2021.12

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 79 ( 3 ) 446 - 452 2021.11

Language：English Publishing type：Research paper (scientific journal)

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Hiroshi Morita, Masakazu Miyamoto

Trends in cardiovascular medicine 32 ( 6 ) 364 - 365 2021.8

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

Language：English Publishing type：Research paper (scientific journal)

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

Expert consensus document on automated diagnosis of the electrocardiogram: The task force on automated diagnosis of the electrocardiogram in Japan. Part 1: Nomenclature for diagnosis and abnormal findings.

Takao Katoh, Masaaki Yashima, Naohiko Takahashi, Eiichi Watanabe, Takanori Ikeda, Yuji Kasamaki, Naokata Sumitomo, Norihiro Ueda, Hiroshi Morita, Masayasu Hiraoka

Journal of arrhythmia 37 ( 4 ) 871 - 876 2021.8

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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

無症候性ブルガダ症候群における心臓突然死のリスク層別化(Risk Stratification for Sudden Cardiac Death in Asymptomatic Brugada Syndrome)

中野由紀子, 廣延直也, 清水渉, 高木雅彦, 森田宏, 相庭武司, 草野研吾, 大野聖子, 鎌倉令, 堀江稔, 高橋尚彦, 篠原徹二, 青沼和隆, 村越伸行, 吉田幸彦

日本循環器学会学術集会抄録集 85回 TP14 - 2 2021.3

Inappropriate Automatic Diagnosis of Atrial Fibrillation in Widely-used Electrocardiograph : Current Situation and Problems

Katoh Takao, Yashima Masaaki, Takahashi Naohiko, Watanabe Eiichi, Ikeda Takanori, Kasamaki Yuji, Sumitomo Naokata, Ueda Norihiro, Morita Hiroshi, Hiraoka Masayasu

Japanese Journal of Electrocardiology 41 ( 1 ) 5 - 13 2021.2

Language：Japanese Publisher：Japanese Heart Rhythm Society

Background : Automatic diagnosis of electrocardiograms（ECG）has been widely used not only in clinical practice but in the health check-ups for more than half a century. However, the diagnostic accuracy of widely-used computer equipped electrocardiograph is not always satisfactory and therefore requires an expert’s over-read. The aim of the present study was to evaluate the current situation and factors that led to inappropriate diagnosis focused on atrial fibrillation（AF）. Method : ECGs with inappropriate computer diagnosis were evaluated carefully by members of The Task Force on Automated Diagnosis of the Electrocardiogram in Japan. Results :（1）Inappropriate diagnosis of AF was found in 54 of 50,000 health check-up ECGs（0.11％）and 51 of 272 consecutive patients（18.8％）at a cardiovascular clinic.（2）Factors of 62 under-diagnoses for AF consisted of 42（67.7％）misdiagnoses of f-wave as sinus P waves, 5（8.1％）as ectopic P waves, 8（12.9％）as atrial flutters and 7（11.3％）of no atrial excitations.（3）Factors of 83 over-diagnoses for AF consisted of 38（45.8％）that missed sinus P waves, 37（44.6％）that overlooked ectopic P waves, and 8（9.6％）that misdiagnosed typical flutter waves. Conclusion : Inappropriate automatic diagnosis of AF may result not only in unnecessary consultations with expert physicians due to over-diagnosis but also increased risk of cerebral infarction or heart failure due to under-diagnosis. The construction of highly accurate and reliable systems by further improving computer algorithms is urgent needly to improve automatic diagnosis of ECG.

DOI： 10.5105/jse.41.5

Other Link： https://www.jstage.jst.go.jp/article/jse/41/1/41_5/_pdf

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1253/circj.CJ-19-0910

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

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

Language：English

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1161/CIRCGEN.120.002926

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1093/europace/euaa003

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1096/fj.201902991R

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1253/circj.CJ-19-0871

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1253/circj.CJ-19-0986

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1253/circj.CJ-19-0968

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

Language：English Publishing type：Research paper (scientific journal)

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

非侵襲検査と基礎医学・工学との融合心電図自動診断の精度評価ならびに有用性向上に関する研究

八島正明, 加藤貴雄, 渡邉英一, 高橋尚彦, 池田隆徳, 笠巻祐二, 住友直方, 植田典浩, 森田宏, 平岡昌和

心電図 40 ( Suppl.2 ) S - 28 2020.2

Fontan患者におけるカテーテルアブレーション(Catheter ablation in Fontan patients)

西井伸洋, 森本芳正, 木村朋生, 宮本真和, 杜徳尚, 中川晃志, 渡邊敦之, 森田宏, 伊藤浩, 重光祐輔, 栄徳隆裕, 馬場健児, 笠原慎吾

日本成人先天性心疾患学会雑誌 9 ( 1 ) 223 - 223 2020.1

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1093/europace/euz207

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

Brugada症候群の新知見 Brugada症候群の心臓突然死リスク予測モデルを用いたリスク階層化

中野由紀子, 廣延直也, 清水渉, 高木雅彦, 森田宏, 草野研吾, 相庭武司, 大野聖子, 鎌倉令, 堀江稔, 木原康樹

日本心臓病学会学術集会抄録 67回 S11 - 2 2019.9

高安病患者に対する経皮的腎血管形成術

小倉聡一郎, 戸田洋伸, 藤本竜平, 大塚寛昭, 森田宏, 伊藤浩

日本心血管インターベンション治療学会抄録集 28回 [MP18 - 005] 2019.9

アンプラッツァーデバイス留置後の心房中隔穿刺

中川晃志, 渡邊敦之, 高谷陽一, 赤木禎治, 森本芳正, 浅田早央莉, 宮本真和, 木村朋生, 西井伸洋, 中村一文, 森田宏, 伊藤浩

日本心血管インターベンション治療学会抄録集 28回 [MO114 - 001] 2019.9

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.2169/internalmedicine.1905-18

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1002/joa3.12164

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.2169/internalmedicine.2076-18

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1007/s11886-019-1170-4

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

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

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

Hiroshi Morita

Heart rhythm 16 ( 2 ) 268 - 269 2019.2

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English

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

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

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

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

Yuko Y Inoue, Takeshi Aiba, Hiro Kawata, Tomoko Sakaguchi, Wataru Mitsuma, Hiroshi Morita, Takashi Noda, Hiroshi Takaki, Keiko Toyohara, Yoshiaki Kanaya, Toshiyuki Itoi, Takeshi Mitsuhashi, Naokata Sumitomo, Yongkeun Cho, Satoshi Yasuda, Shiro Kamakura, Kengo Kusano, Yoshihiro Miyamoto, Minoru Horie, Wataru Shimizu

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

Language：English Publishing type：Research paper (scientific journal)

Aims: Andersen-Tawil Syndrome (ATS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are both inherited arrhythmic disorders characterized by bidirectional ventricular tachycardia (VT). The aim of this study was to evaluate the diagnostic value of exercise stress tests for differentiating between ATS and CPVT. Methods and results: We included 26 ATS patients with KCNJ2 mutations from 22 families and 25 CPVT patients with RyR2 mutations from 22 families. We compared the clinical and electrocardiographic (ECG) characteristics, responses of ventricular arrhythmias (VAs) to exercise testing, and the morphology of VAs between ATS and CPVT patients. Ventricular arrhythmias were more frequently observed at baseline in ATS patients compared with CPVT patients [the ratio of ventricular premature beats (VPBs)/sinus: 0.83 ± 1.87 vs. 0.06 ± 0.30, P = 0.01]. At peak exercise, VAs were suppressed in ATS patients, whereas they were increased in CPVT patients (0.14 ± 0.40 vs. 1.94 ± 2.71, P < 0.001). Twelve-lead ECG showed that all 25 VPBs and 15 (94%) of 16 bidirectional VTs were right bundle branch block (RBBB) morphology in ATS patients, whereas 19 (86%) of 22 VPBs had left bundle branch block (LBBB), and 12 (71%) of 17 bidirectional VT had LBBB and RBBB morphologies in CPVT patients. Conclusion: In patients with ATS, VAs with RBBB morphology were frequently observed at baseline and suppressed at peak exercise. In contrast, exercise provoked VAs with mainly LBBB morphology in patients with CPVT. In adjunct to clinical and baseline ECG assessments, exercise testing might be useful for making the diagnosis of ATS vs. CPVT, both characterized by bidirectional VT.

DOI： 10.1093/europace/eux351

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

Language：English Publishing type：Research paper (scientific journal)

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

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

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

Hot topics in Brugada syndrome. International journal

Hiroshi Morita

Heart rhythm 15 ( 9 ) 1402 - 1403 2018.9

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.jacep.2018.02.009

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1253/circj.CJ-17-0747

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1111/jce.13336

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1111/jce.13349

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1111/jce.13315

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

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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

心房中隔欠損症患者における心房細動に対するカテーテルアブレーションの長期転帰(Long-term Outcome of Catheter Ablation for Atrial Fibrillation in Patients with Atrial Septal Defect)

中川晃志, 赤木禎治, 永瀬聡, 高谷陽一, 森本芳正, 川田哲史, 橘元見, 渡辺敦之, 西井伸洋, 中村一文, 森田宏, 伊藤浩

日本循環器学会学術集会抄録集 81回 PJ - 399 2017.3

労作時低酸素血症を合併したEbstein奇形に対する経皮的卵円孔閉鎖術

三木崇史, 赤木禎治, 高谷陽一, 麻植浩樹, 社徳尚, 中川晃志, 中村一文, 森田宏, 伊藤浩

日本成人先天性心疾患学会雑誌 6 ( 1 ) 118 - 118 2017.1

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

Language：English Publishing type：Research paper (scientific journal)

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

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

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.hrthm.2016.03.044

チアノーゼ型心疾患術後に生じた肺動静脈瘻のAmplatzer Vascular Plug IIによる塞栓術

三木崇史, 赤木禎治, 高谷陽一, 麻植浩樹, 中川晃志, 中村一文, 森田宏, 伊藤浩

日本成人先天性心疾患学会雑誌 5 ( 1 ) 114 - 114 2016.1

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

Language：Japanese Publisher：公益財団法人日本心臓財団

<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

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1253/circj.CJ-15-0618

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

Language：English Publishing type：Research paper (scientific journal)

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

成人先天性心疾患に伴う不整脈の特徴と最新の治療心房中隔欠損と心房細動の治療の最前線

中川晃志, 永瀬聡, 赤木禎治, 木島康文, 高谷陽一, 西井伸洋, 河野晋久, 中村一文, 森田宏, 伊藤浩

日本心臓病学会学術集会抄録 62回 JS3 - 3 2014.9

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.jacc.2014.01.072

左室側壁心外膜側に不整脈基質が存在すると考えられたJ波症候群の1例

中川晃志, 永瀬聡, 和田匡史, 田中正道, 西井伸洋, 寒川睦子, 河野晋久, 中村一文, 森田宏, 草野研吾, 伊藤浩, 湯本晃久, 向原直木, 大江透

臨床心臓電気生理 37 127 - 135 2014.5

Language：Japanese Publisher：臨床心臓電気生理研究会

症例は52歳、男性。以前より心電図にて早期再分極が認められていた。心室細動自然発作を来たしたため、当院入院。心電図ではI、II、aVl、aVf、V4-6にJ波を認めた。心臓電気生理学的検査において、多極カテーテルにて経冠静脈的に左室側壁心外膜側の電位を記録すると、単極および双極誘導において体表面心電図のJ波に相当する成分が記録され、この成分は心房頻回刺激およびisoproterenolにて減高し、pilsicainideにて増強を示した。一方、前室間静脈、中心静脈、左室側壁心内膜側からの記録ではJ波に相当する成分は記録されず、また心室プログラム刺激にて心室細動は右室心尖部、右室流出路、左室心内膜側からは誘発されず、左室側壁心外膜側からのみ誘発された。Pilsicainide投与後は左室心外膜側起源と思われる期外収縮が散発し、Brugada型波形は出現しなかった。本例はJ波症候群Type 1+2と考えられ、左室側壁心外膜側の電気的異常が病態の成因に関与することが示唆された興味深い1例と考えられたので報告する。(著者抄録)

心臓突然死予知への挑戦サルコイドーシスにおけるlateral領域のfragmented QRSは心室頻拍の予測因子となる

武寛, 森田宏, 伴場主一, 廣畑敦, 中村一文, 草野研吾, 山本桂三, 大江透, 伊藤浩

心電図 34 ( Suppl.2 ) S - 35 2014.3

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

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

右室単発早期刺激により明瞭なcoved型そしてsaddleback型心電図が得られたBrugada症候群の1例

中川晃志, 永瀬聡, 和田匡史, 田中正道, 西井伸洋, 渡邊敦之, 中村一文, 森田宏, 河野晋久, 草野研吾, 大江透, 伊藤浩

心臓 45 ( Suppl.3 ) 143 - 148 2013.12

Language：Japanese Publisher：(公財)日本心臓財団

症例は62歳、男性。早朝の苦悶様呼吸に続く呼吸停止疑いのため近医受診し、Brugada症候群疑いにて当院紹介入院。心電図では完全右脚ブロックを合併することもありBrugada型心電図との診断が容易ではなかった。電気生理学的検査時、ピルジカイニド1mg/kgを投与したが、やはり明瞭なBrugada型波形が得られないため、完全右脚ブロックの状態を是正する目的で右室心尖部より単発早期刺激を加えた。すると刺激間隔の短縮に伴いcoved型そしてsaddleback型の比較的明瞭なBrugada型心電図を得ることができた。完全右脚ブロックを伴いBrugada型心電図の診断が困難であったが右室心尖部単発早期断激によりBrugada型心電図が明瞭化され、また、相対的な右室伝導遅延の改善に伴いcoved型からsaddleback型に心電図が変化したBrugada症候群の1例を経験したので報告する。(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2013&ichushi_jid=J00679&link_issn=&doc_id=20131216220028&doc_link_id=10.11281%2Fshinzo.45.S3_143&url=https%3A%2F%2Fdoi.org%2F10.11281%2Fshinzo.45.S3_143&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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

CPAを発症したLQTS症例の臨床像の特徴

寒川睦子, 森田宏, 河野晋久, 永瀬聡, 西井伸洋, 中村一文, 草野研吾, 伊藤浩, 大江透, 氏家良人

心電図 33 ( Suppl.4 ) S - 172 2013.9

QT延長症候群の診断に苦慮した1例

高谷陽一, 森田宏, 麻植浩樹, 杜徳尚, 吉田賢司, 谷山真規子, 三好亨, 西井伸洋, 永瀬聡, 中村一文, 河野普久, 草野研吾, 伊藤浩

心電図 33 ( Suppl.4 ) S - 154 2013.9

治療に苦慮した先天性QT延長症候群(LQT3)の1例

野田陽子, 森田宏, 三浦大志, 高谷陽一, 和田匡史, 中川晃志, 西井伸洋, 永瀬聡, 伊藤浩

心電図 33 ( Suppl.4 ) S - 153 2013.9

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.hrthm.2013.04.009

BAL所見が診断に有用であった持続性心室頻拍を伴う心室瘤の1例

和田匡史, 草野研吾, 西井伸洋, 永瀬聡, 森田宏, 中村一文, 河野晋久, 伊藤浩

心臓 45 ( Suppl.2 ) 91 - 91 2013.8

サルコイドーシスにおける心室頻拍の予測因子

武寛, 森田宏, 伴場主一, 大原美奈子, 廣瀬英軌, 廣畑敦, 草野研吾, 山本桂三, 大江透, 伊藤浩

心臓病センター榊原病院雑誌 17 14 - 18 2013.8

Language：Japanese Publisher：心臓病センター榊原病院

サルコイドーシスにおける心室頻拍の予後予測因子として、fragmented QRS(fQRS)が関連するか検討した。心臓サルコイドーシス50例(心サ)、全身性サルコイドーシス71例(全サ)であった。心サ群では、房室ブロックを66%に認め、心機能も有意に低値であった。心サ群50例のうち、初診時に心室頻拍を認めたのは19例であった。fQRSの存在は、心サ群と全サ群とも有意差を認めなかったが、局在性をみると、前壁(52%対30%)、側壁(54%対14%)で有意差を認めた。下壁のfQRSは、全サ群にも多く認め、前壁、側壁のfQRSが心サ群に関連している可能性が考えられた。心サ群の11例が再発、無症候性31例のうち6例に心室頻拍の新規発症を認めた。全サ群からの心室頻拍発症は認めなかった。前壁(68%対31%)、側壁(60%対23%)のfQRSはVT群で有意に高値であった。

Ion channel complex disease in long QT syndrome. International journal

Hiroshi Morita

Heart rhythm 10 ( 5 ) 738 - 9 2013.5

Brugada症候群の夜間・徐脈時の心室遅延電位の特徴の検討

寒川睦子, 森田宏, 永瀬聡, 西井伸洋, 河野晋久, 中村一文, 草野研吾, 伊藤浩, 亀井成美, 青木佐知子, 越智真金, 信定さおり, 川下隆二, 岡田健, 大江透

心電図 33 ( Suppl.2 ) S - 29 2013.5

メタボリックシンドローム患者におけるベザフィブラートの血管内皮機能への影響

大野佑子, 麻植浩樹, 三好亨, 杜徳尚, 河野晋久, 中村一文, 永瀬聡, 森田宏, 草野研吾, 伊藤浩

超音波医学 40 ( Suppl. ) S703 - S703 2013.4

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

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMED CENTRAL LTD

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.

DOI： 10.1186/1475-2840-12-8

最大径40mmを越す心房中隔欠損症をいかにカテーテル閉鎖するか?利尿剤投与の効果

上岡亮, 木島康文, 赤木禎治, 杜徳尚, 中川晃志, 永瀬聡, 河野晋久, 森田宏, 草野研吾, 伊藤浩

日本成人先天性心疾患学会雑誌 2 ( 1 ) 70 - 70 2013.1

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Hiroshi Morita

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

Andersen-Tawil症候群に合併した心室性不整脈に対し各種薬効評価を行い得た1例

重歳正尚, 草野研吾, 武寛, 永瀬聡, 森田宏, 伊藤浩

心臓 44 ( Suppl.3 ) 29 - 35 2012.12

Language：Japanese Publisher：(公財)日本心臓財団

Andersen-Tawil症候群(ATS)は不整脈・周期性四肢麻痺・形態異常を特徴とする稀な遺伝性疾患である。今回、ATSに合併した心室性不整脈に対して各種薬物効果を確認したので報告する。症例は47歳の女性。幼少時より多源性・多発性の心室期外収縮による頻脈・失神歴があり、最近はピルジカイニド100mg/日を内服されていた。2011年動悸が悪化し他院へ入院。その際の遺伝子検査にてKCNJ2遺伝子に既報のミスセンス変異を認め、ATSと診断され、精査加療のため当院へ入院となった。フレカイニド、ピルジカイニド、フェントラミン、ベラパミル静脈投与で著明な心室期外収縮抑制効果を認めたが、β遮断薬は無効であった。心臓電気生理学的検査では持続性心室頻拍や心室細動は誘発されなかった。自然発生の心室期外収縮に対して良好なペースマップが得られた部位で通電したが、すぐに再発し、アブレーションの効果は乏しいと判断した。その後、スピロノラクトン、イコサペント酸、フレカイニド200mgの内服で著明に心室期外収縮数が減少し、症状の劇的な改善を認めた。(著者抄録)

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1161/CIRCEP.111.970285

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

Fragmented QRS: What Is The Meaning? International journal

Yutaka Take, Hiroshi Morita

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

Language：English Publishing type：Research paper (scientific journal)

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.

24時間ホルター心電図を用いた、Brugada症候群、特発性心室細動、健常者の心室遅延電位(LP)の特徴の検討

寒川睦子, 森田宏, 永瀬聡, 西井伸洋, 河野晋久, 中村一文, 草野研吾, 伊藤浩, 大江透

心電図 32 ( Suppl.5 ) S - 180 2012.9

Brugada症候群におけるspontaneous type1波形を呈さないハイリスク群の検討

和田匡史, 森田宏, 三好亨, 西井伸洋, 橋本克史, 永瀬聡, 中村一文, 河野晋久, 草野研吾, 伊藤浩

心電図 32 ( Suppl.5 ) S - 156 2012.9

Brugada症候群患者における心室細動のリスクとしての下壁側壁誘導の早期再分極(ER)とFragmented QRS

時岡浩二, 草野研吾, 森田宏, 永瀬聡, 西井伸洋, 中村一文, 河野晋久, 伊藤浩

心電図 32 ( Suppl.5 ) S - 158 2012.9

左室拡張不全のリスクマーカーとしての冠動脈石灰化スコア冠動脈有意狭窄を認めない例での検討

三好亨, 大澤和宏, 麻植浩樹, 杜徳尚, 永瀬聡, 河野晋久, 中村一文, 森田宏, 草野研吾, 伊藤浩

日本高血圧学会総会プログラム・抄録集 35回 471 - 471 2012.9

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

Language：English Publishing type：Research paper (scientific journal)

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

不整脈と心臓病理形態学器質的心疾患に伴う心室性不整脈の特徴と対策

草野研吾, 永瀬聡, 森田宏, 中村一文, 伊藤浩, 大江透

日本心臓病学会誌 7 ( Suppl.I ) 219 - 219 2012.8

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

Language：English Publishing type：Research paper (scientific journal)

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

電気的ストームの実態と対処 Brugada症候群における植込み型除細動器頻回作動に対する抗不整脈薬の長期的効果

草野研吾, 永瀬聡, 森田宏, 中村一文, 西井伸洋, 田中正道, 中川晃司, 三浦大治, 伊藤浩

Journal of Arrhythmia 28 ( Suppl. ) 160 - 160 2012.5

Brugada症候群での高リスク失神の特徴

武寛, 森田宏, 杜徳尚, 西井伸洋, 永瀬聡, 中村一文, 草野研吾, 大江透, 伊藤浩

心電図 32 ( Suppl.2 ) S - 46 2012.5

Brugada症候群ではピルジカイニド負荷により、心室間非同期が惹起される

杜徳尚, 森田宏, 西井伸洋, 永瀬聡, 中村一文, 草野研吾, 伊藤浩

Journal of Arrhythmia 28 ( Suppl. ) 312 - 312 2012.5

Fragmented QRSは左心機能低下例で心機能改善の予測因子となる

武寛, 伴場主一, 大江透, 森田宏, 西井伸洋, 永瀬聡, 中村一文, 草野研吾, 伊藤浩

Journal of Arrhythmia 28 ( Suppl. ) 333 - 333 2012.5

リモートモニタリングの活用チームで運用するリモートモニタリングの利点、問題点について

久保元基, 西井伸洋, 永瀬聡, 草野研吾, 伊藤浩, 竹中祐樹, 森田宏

Journal of Arrhythmia 28 ( Suppl. ) 185 - 185 2012.5

心不全症例では植込み型除細動器による心腔内除細動により心機能が低下し、血行動態の回復は遅延する

杜徳尚, 西井伸洋, 森田宏, 永瀬聡, 中村一文, 河野晋久, 草野研吾, 伊藤浩

Journal of Arrhythmia 28 ( Suppl. ) 242 - 242 2012.5

不整脈源性右室心筋症の診断にて右室心外膜起源の心室頻拍に対する心内膜側・心外膜側カテーテルアブレーションを施行した症例の剖検心の検討

田中正道, 中川晃志, 西井伸洋, 永瀬聡, 中村一文, 森田宏, 河野邦久, 草野研吾, 伊藤浩, 由谷親夫

Journal of Arrhythmia 28 ( Suppl. ) 410 - 410 2012.5

重症心不全に伴う不整脈の薬物治療

中村一文, 中川晃志, 杉山洋樹, 森田宏, 草野研吾, 伊藤浩

呼吸と循環 60 ( 4 ) S2 - S4 2012.4

心不全を合併した心房細動症例に対する経口アミオダロンの効果

三好章仁, 草野研吾, 中川晃志, 西井伸洋, 永瀬聡, 中村一文, 森田宏, 伊藤浩

Progress in Medicine 32 ( Suppl.1 ) 464 - 467 2012.3

Language：Japanese Publisher：(株)ライフ・サイエンス

心不全を合併した心房細動症例に対するアミオダロンの効果、安全性について検討した。心室性不整脈に対してアミオダロンを処方した124例を対象とした。処方時に発作性・持続性心房細動を合併していた症例は43例で、そのうち6ヵ月間経過観察できた心房細動症例は30例であった。アミオダロン投与による洞調律維持は18例で可能であった。洞調律維持群をsinus群、洞調律に回復しなかった群をAF群として検討した。LVEFはAF群では改善する傾向がみられた。心拍数はsinus群で低下傾向を示した。LADは両群ともに変化は認めなかった。BNP値はsinus群で有意に低下し、AF群では低下傾向を示した。KL-6は投与前後で有意差を認めず、KL-6が急上昇した1例は、CT所見で間質の線維化を認めたためアミオダロン投与を中止し、KL-6は投与前の数値にまで回復した。

Brugada症候群における下壁側壁誘導でのJ waveの意義 Brugada症候群における下壁側壁誘導での早期再分極の影響

時岡浩二, 草野研吾, 谷山真規子, 杜徳尚, 吉田賢司, 三好亨, 西井伸洋, 永瀬聡, 中村一文, 河野晋久, 森田宏, 伊藤浩, 大江透

心電図 32 ( Suppl.1 ) S - 87 2012.2

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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

PSL単独での治療に難渋し、MTX併用が有用であった心サルコイドーシスの1例

三好章仁, 草野研吾, 久保元基, 西井伸洋, 永瀬聡, 河野晋久, 森田宏, 伊藤浩

日本サルコイドーシス/肉芽腫性疾患学会雑誌 31 ( サプリメント号 ) 40 - 40 2011.10

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.3390/ph4081088

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

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER IRELAND LTD

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 < 0.05) and apolipoprotein B-48 (apoB-48) concentrations (r = -0.551, P < 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 < 0.05), remnant lipoprotein cholesterol (from 66.9 +/- 27.6 to 38.9 +/- 15.4 mg h/dl, P < 0.01) and apoB-48 (from 58.8 +/- 27.5 to 36.2 +/- 17.0 mu gh/ml, P < 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 < 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.

DOI： 10.1016/j.atherosclerosis.2011.04.019

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

Language：English Publishing type：Research paper (scientific journal) Publisher：EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC

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 (>= 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 <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 <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 <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)

DOI： 10.1016/j.amjcard.2011.03.049

How can we stabilize QT variability? International journal

Hiroshi Morita

Heart rhythm 8 ( 8 ) 1243 - 4 2011.8

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.hrthm.2011.02.009

心臓突然死予知のための新しい診断法 Fragmented QRSによるBrugada症候群突然死の予知

森田宏, 永瀬聡, 草野研吾, 大江透, 伊藤浩

心電図 31 ( Suppl.1 ) S - 36 2011.5

左室心外膜側にて著明なJ波とOut of QRS Potentialが記録されたBrugada症候群(J Wave Syndrome)の1例

田中正道, 永瀬聡, 中川晃志, 多田毅, 村上正人, 西井伸洋, 中村一文, 幡芳樹, 森田宏, 河野晋久, 草野研吾, 伊藤浩, 大江透

臨床心臓電気生理 34 205 - 215 2011.5

Language：Japanese Publisher：臨床心臓電気生理研究会

症例は39歳、男性。心室細動自然発作を認めるBrugada症候群との診断で当院入院。心電図ではV2でのsaddle back型ST上昇とI、II、aV1、V3-6でのJ波を認めた。心臓電気生理学的検査では、経冠静脈的に左室側壁心外膜側に多極カテーテルを挿入し電位の記録を行ったところ、単極誘導では明瞭なJ波が記録され、双極誘導ではJ波の成分に伴いout of QRS potentialが記録された。単極誘導でのJ波は心房ペーシング、およびisoproterenol投与で減高し、pilsicainide投与で増高した。また双極誘導でのout of QRS電位は心房ペーシングおよびisoproterenol投与で短縮しpilsicainide投与で延長した。再分極異常の性質を示す左室心外膜側J波がout of QRS potentialとしても記録され、J wave syndromeの成因を考えるうえで興味深い症例と考えられここに報告する。(著者抄録)

53歳女性Brugada症例のLate Potential(LP)と心拍変動との関連性、LPの日内変動性の検討ホルター心電図を用いて

寒川睦子, 豊永慎二, 間島圭一, 中津高明, 藤田政雄, 草地省蔵, 大江透, 西井伸洋, 永瀬聡, 森田宏, 中村一文, 草野研吾, 伊藤浩

心電図 31 ( Suppl.1 ) S - 20 2011.5

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

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

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

Language：English Publisher：Japanese Heart Rhythm Society

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.

DOI： 10.4020/jhrs.27.OP36_2

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1371/journal.pone.0019897

Pronounced Late Potential at Night Time, Bradycardia, and Pronounced Vagal Activity May Be a Risk Marker of Ventricular Fibrillation in Brugada Syndrome

Mutsuko Sangawa, Hiroshi Morita, Nobuhiro Nishii, Sastoshi Nagase, Kazufumi Nakamura, Kengo Kusano, Hiroshi Ito

journal of arrhythmia 27 ( 4 ) 280 2011

Publishing type：Research paper (scientific journal)

Backgrond: Ventricular Late Potential(LPs) detected signal averaged ECGs have been used widely to detect high risk patients. In Brugada syndrome(BrS), Ventricular fibrillation(VF) frequently occurs at nighttime and pronounced vagal activity. Purpose: We examine relationship between LPs and Heart rate, Vagal activity, and circadian variation of LPs in BrS. Methods: We evaluated 24hours HolterECGs of total 14 BrS and 10 normal controls. We evaluated LPs (fQRS,LAS40,RMS40), RR interval and High frequency (HF:0.15-0.4Hz) of frequency domaine analysis. We examined relationship between LPs and RRinterval, LnHF. Results: Relationship between LAS40 and RRinterval, relationship between LAS40 and LnHF were obtained as a liner regression line and significant positive correlation inBrS. LAS40/RRslope was significantly sharpened in BrSwithVF than BrSwithout VF, Controls (24 ±11 vs 3±13 vs -4±20, p<0.01, BrSwithVF vs BrSwithoutVF vs Controls). LAS40 at bradycardia was significantly pronounced in BrS withVF than BrS withoutVF, Controls (48±3 vs 32±12 vs 22±11, p<0.01, BrS withVF vs BrS withoutVF vs Controls). LAS40/LnHFslope were significantly sharpened than Controls.(3.0±3.2 vs -0.4±3.0, p<0.05, BrS vs Controls). Conclusion: In BrS, LPs were pronounced at bradycardia and night time and at pronounced vagal acitivity. Pronounced LPs at bradycardia and nighttime, at pronounced vagalacitivity may be a risk marker of VF inBrS. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.OP36_4

J Waves in Patients with Vasospastic Angina

Koji Nakagawa, Satoshi Nagase, Masamichi Tanaka, Nobuhiro Nishii, Hiroshi Morita, Kunihisa Kohno, Kengo Kusano, Tohru Ohe, Hiroshi Ito

journal of arrhythmia 27 191 2011

Publishing type：Research paper (scientific journal)

Objectives: The purpose of this study was to determine whether J wave is a marker of arrhythmic risk in patients with vasospastic angina (VSA). Background: Both VSA and the presence of J waves in ECG are associated with fatal ventricular arrhythmias and sudden death. However, the prevalence of J waves among VSA patients is little known. Methods: We reviewed 66 patients with VSA in our hospital retrospectively and assessed the association between the presence of J wave and clinical backgrounds among them. J wave was defined as an elevation of the QRS-ST junction of > 0.1mV from baseline. Results: Spontaneous VF and syncope occurred in 9 (13.6%) and 14 (21.2%) of all patients, respectively. J waves were observed in 33 patients (50%) and were significantly more prevalent in males than females (60.4% vs. 16.7%, Pμ0.01). Arrhythmic symptoms (ventricular arrhythmias or syncope) were observed frequently in patients with J waves, compared to without J wave (48.4% vs. 23.8%, Pμ0.05). Both of the locations and height of J waves were not associated with the history of arrhythmic symptoms. Conclusions: J waves are observed frequently among male patients with VSA. The presence of J waves potentially influence the development of lethal ventricular arrhythmias associated with VSA. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.OP03_4

Impact of Infero/Lateral Early Repolarization Pattern in Patients with Brugada Syndrome

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

journal of arrhythmia 27 ( 4 ) 286 2011

Publishing type：Research paper (scientific journal)

Background: Inferolateral early repolarization (ER) pattern is often observed in Brugada syndrome (BrS). However, its clinical implication in this syndrome is still controversial. Method: Total two-hundred forty five Brugada ECG patients (mean age 48 years, men/female=235/10), including documented ventricular fibrillation (VF) in 27, were evaluated. Infero/lateral ER pattern was defined as a notched or slurring>1mm J-wave at least consecutive two of inferior (II, III, aVF) or lateral (I, aVL, V4, V5, V6) leads. The presence of this ER pattern was compared with clinical, electrocardiographic and genetic parameters. Results: Infero/lateral ER pattern was observed in 25 (10.2%) BrS patients (inferior leads in 12, lateral leads in 11 and both in 2) and was significantly associated with patients of documented VF (P<0.01) and with prolonged PQ interval (P<0.04). However they were not associated with the frequency of spontaneous type-1 ECG, wide QRS complex (>120ms), family history of sudden death, positive late potential on signal averaged ECG and SCN5A mutation. Increased number of positive ER leads have a trend of increasing documented VF patients (>3 leads; 54%). Conclusion: These data indicates that infero/lateral ER reflects the expansion of repolarization abnormality in the ventricle and may be associated with high-risk phenotype in BrS. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.CP1_07

PJ3-053 New Onset of Ventricular Fibrillation Episodes in Asymptomatic Patients with Brugada Syndrome -Are Patients with Class IIb Safe?-

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

Journal of Arrhythmia 27 2011

Publishing type：Research paper (scientific journal)

Introduction: Japanese guideline of the Brugada syndrome (BS) defined the indication of the implantable cardioverter defibrillater (ICD) in asymptomatic patients with BS as patients having both family history of sudden death (FH) and induced ventricular fibrillation (VF) by programmed electrical stimulation (PES) (class IIa). When patients had one of these criteria, ICD indication considered as class IIb. We analyzed new onset of VF episodes in asymptomatic patients. Methods and Results: We analyzed 99 asymptomatic patients with Brugada type ECG. Fourty-seven patients had FH. VF was induced by PES in 44 patients. Criteria of ICD indication of class IIa, IIb, and III were met in 20, 50, and 29 patients, respectively. Three patients experienced new-onset VF episode during follow-up periods (84±43 months). Although there was no new-onset VF in patients with class IIa, all patients who experienced VF episodes belonged to class IIb (6%). All patients with new-VF had spontaneous type 1 ECG, induced VF by PES, positive late potential and fragmented QRS, but did not have FH and SCN5A mutation. Conclusion: Prediction of prognosis in patients with BS-ECG based on BS-guideline has limited value and occurrence of VF is not rare in patients with class IIb of ICD indication. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.PJ3_053

J Wave in Brugada Syndrome

Wataru Shimizu, Hiro Kawata, Shiro Kamakura, Hiroshi Morita

journal of arrhythmia 27 ( 4 ) 250 2011

Language：English Publishing type：Research paper (scientific journal)

J wave in inforo/ateral leads is more frequently recognized in patients (pts) with idiopahtic ventricular fibrillation (IVF) than in control subjects, and a new concept of early repolarization syndrome or J wave syndrome has been proposed. Brugada syndrome is characterized by ST-segment elevation in the right precordial leads. In our cohort of 49 Brugada pts with documented VF (46 males, 46±13years), J wave was recorded persistently in 15 pts (30.6%, P-group), intermittently in 16 pts (32.6%, I-group), and never recorded in 18 pts (36.7%, N-group). During follow-up period (7.7 ±3.8 years), VF recurred in all 15 pts with P-group (100%), and less in 12 pts with I-group (75%, p=0.11, log rank test) and in 8 pts with N-group (44%, p=0.0001, log rank test). These data suggest higher prevalence of J wave (31/49, 63.2%) in Brugada synforme with documented VF and a significant association between J wave and VF in Brugada syndrome. J wave amplitude in the infero/lateral leads was attenuated with sodium channel blocker in most Brugada pts, whereas ST-segment elevation was augmeted or coved type (type 1) ECG was unmasked in the right precordial leads, indicating the differential mechanism between the ST-segment elevation in the right precordial leads and J wave in the infero/lateral leads in Brugada syndrome. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.STL_4

Identification of High-Risk Syncope Related to Ventricular Fibrillation in Patients with Brugada Syndrome

Yutaka Take, Hiroshi Morita, Satoshi Nagase, Nobuhiro Nishii, Kazuhumi Nakamura, Kengo Kusano, Tohru Ohe, Hiroshi Itoh

journal of arrhythmia 27 ( 4 ) 209 2011

Language：English Publishing type：Research paper (scientific journal)

Background:Syncope in patients with Brugada syndrome (BS) is usually associated with ventricular tachyarrhythmia. However, some episodes of syncope could be related to autonomic disorders. We investigated the characteristics of syncope to differentiate high-risk syncope episodes from low-risk events. Methods and Results: Eighty patients with type 1 ECG and syncope were divided into two groups: patients with prdoromes (Prodromal group, N=40) and without prodromes (Non-prodromal group, N=40). Ventricular fibrillation (VF) was documented at initial episodes in 17 patients. Only 3 patients experienced prodromes before the onset of VF and 14 patients did not have prodromes (P=0.0023). Twenty-seven patients in the Prodromal group and 6 patients in the Non-prodromal group were considered to have syncope related to autonomic dysfunction. Recurrent syncope due to VF was more frequent in the Non-prodromal group (N=9) than in the Prodromal group (N=2
P=0.023) during the follow-up period (50±48months). Multivariate logistic regression analysis indicated that blurred vision (Hazard ratio 0.092) and existence of f-QRS (Hazard ratio 2.99) were independently associated with the occurrence of VF. Conclusion: Syncope without prodromes, especially blurred vision, and existence of fragmented QRS are high-risk signs for occurrence of VF in patients with BS. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.OP18_2

Intrathoracic Impedance Is Negatively Correlated with BNP Value in Patients with Implantable Cardioverter Defibrillator: MOMOTARO Study

Atsuyuki Watanabe, Nobuhiro Nishii, Yoji Okamoto, Satoki Fujii, Tadashi Wada, Motoki Kubo, Hiroshi Morita, Kengo Fukushima, Hiroshi Ito

journal of arrhythmia 27 ( 4 ) 299 2011

Language：English Publishing type：Research paper (scientific journal)

Introduction: Heart failure is one of the most common causes for hospitalizations. OptiVol alert, which was fluid status algorism calculated from intrathoracic impedance, may detect impending fluid accumulation. Then, we tried to examine the relationship of OptiVol alert or intrathoracic impedance with various parameters. Methods: The patients who were implanted high energy device with OptiVol feature were included in this study. The patients were evaluated various examinations at enrolment and following an OptiVol alert. We examined how various parameters were different between baseline and OptiVol alert. and the relationships among the factors included in OptiVol alert and intrathoracic impedance were evaluated by factor analysis. Results: From April in 2010, 191 patients were eligible for the present study. In all patients, there was no significant difference in all parameters between OptiVol alert and baseline. However, in the patients with ejection fraction less than 35%, BNP value was likely to increase in OptiVol alert compared with that in baseline, but not significantly. In factor analysis, there was no parameter correlated with OptiVol alert. However, intrathoracic impedance was negatively correlated with BNP value. Conclusions: Intrathoracic impedance, but OptiVol alert, seems to represent fluid retention. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.PJ2_053

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.hrthm.2010.09.008

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.jccase.2010.06.003

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.yjmcc.2010.07.012

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1097/FJC.0b013e3181f03c2f

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

53歳女性Brugada症例のホルター心電図を用いた加算平均心電図指標(Late Potential)と心拍変動との関連、日内変動の検討

寒川睦子, 藤田政雄, 豊永慎二, 間島圭一, 中津高明, 草地省蔵, 森田宏, 西井伸洋, 永瀬聡, 中村一文, 大江透, 草野研吾, 伊藤浩

心電図 30 ( Suppl.4 ) S - 171 2010.9

小開胸心外膜アプローチにて心室頻拍に対するアブレーションを行った不整脈源性右室心筋症の1例

田中正道, 永瀬聡, 中川晃志, 村上正人, 西井伸洋, 森田宏, 草野研吾, 伊藤浩, 高垣昌己, 佐野俊二

心電図 30 ( Suppl.4 ) S - 201 2010.9

健常人におけるホルター心電図を用いた加算平均心電図指標と心拍変動との関連性の検討

寒川睦子, 藤田政雄, 豊永慎二, 間島圭一, 中津高明, 草地省蔵, 森田宏, 西井伸洋, 永瀬聡, 中村一文, 大江透, 草野研吾, 伊藤浩

心電図 30 ( Suppl.4 ) S - 196 2010.9

遅延電位の24時間Holter心電図記録を用いたBrugada症候群の速度依存性脱分極のダイナミクス(Rate-dependent depolarization dynamics in Brugada syndrome using 24hours Holter recordings of Late Potential)

寒川睦子, 藤田政雄, 豊永慎二, 間島圭一, 中津高明, 草地省蔵, 森田宏, 西井伸洋, 永瀬聡, 中村一文, 大江透, 草野研吾, 伊藤浩

心電図 30 ( Suppl.4 ) S - 197 2010.9

植え込み型除細動器による心腔内除細動が心筋組織・心機能にあたえる影響についての検討

杜徳尚, 西井伸洋, 中村一文, 永瀬聡, 河野晋久, 森田宏, 草野研吾, 伊藤浩

日本心臓病学会誌 5 ( Suppl.I ) 291 - 291 2010.8

Remote ischemic preconditioning(RIPC)により血管弛緩反応が惹起される

圓光賢希, 中村一文, 柚木佳, 杜徳尚, 三好亨, 西井伸洋, 永瀬聡, 河野晋久, 森田宏, 草野研吾, 伊藤浩, 寒川睦子

日本心臓病学会誌 5 ( Suppl.I ) 257 - 257 2010.8

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.hrthm.2010.01.039

上大静脈と下大静脈の周囲を興奮が各々旋回するDual-Loop Reentryによる術後心房頻拍の1例

多田毅, 永瀬聡, 村上正人, 平松茂樹, 田中正道, 中川晃志, 西井伸洋, 中村一文, 幡芳樹, 森田宏, 草野研吾, 伊藤浩, 大江透

臨床心臓電気生理 33 21 - 29 2010.5

Language：Japanese Publisher：臨床心臓電気生理研究会

症例は32歳、女性。開胸術の既往があり、頻拍発作を主訴に来院。心電図にて心房頻拍を認めアブレーション目的に入院。CARTOを用いたvoltage mappingにて右房側壁は強く障害され、activation mappingにて右房内興奮は右房側壁を前方より後方へ伝播し、後壁を横断、中隔を後方から前方へ伝播した後、三尖弁-上大静脈間、いわゆるupper-loopと三尖弁-下大静脈間、いわゆるlower-loopを伝播した。以上より右房側壁にcommon channelを持ち、upper loopとlower loopを同時に旋回するdual-loop reentryと診断した。Common channelでfragmented electrogramが記録され、同部位の通電で速やかに頻拍は停止した。上大静脈と下大静脈周囲を興奮が各々旋回するまれなdual-loop reentryの1例と考える。(著者抄録)

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1093/europace/eup432

サンリズム負荷にて右室流出路起源の単形性心室頻拍を呈したBrugada症候群の1症例

久保元基, 西井伸洋, 永瀬聡, 森田宏, 幡芳樹, 中村一文, 草野研吾, 伊藤浩

Journal of Arrhythmia 26 ( Suppl. ) 348 - 348 2010.4

ここまで進んだ不整脈の遺伝子診断日本人におけるカテコラミン誘発性多形性心室頻拍の臨床的特徴とリアノジン受容体遺伝子異常の関連性

河田宏, 山田優子, 岡村英夫, 野田崇, 里見和浩, 須山和弘, 相原直彦, 鎌倉史郎, 清水渉, 宮本恵宏, 森田宏, 草野研吾, 住友直方

Journal of Arrhythmia 26 ( Suppl. ) 157 - 157 2010.4

「Shock Reduction」ICD頻回作動を回避するためにアルゴリズム・抗不整脈薬の活用と工夫植込み型除細動器を植込まれたBrugada症候群患者における適切作動、不適切作動の検討

西井伸洋, 久保元基, 中川晃司, 田中正道, 多田毅, 村上正人, 永瀬聡, 中村一文, 幡芳樹, 河野晋久, 森田宏, 草野研吾, 伊藤浩

Journal of Arrhythmia 26 ( Suppl. ) 181 - 181 2010.4

ここまで進んだ不整脈の遺伝子診断 Brugada症候群患者における表現型から遺伝型の予測

森田宏, 永瀬聡, 杜徳尚, 西井伸洋, 中村一文, 幡芳樹, 草野研吾, 伊藤浩, 大江透

Journal of Arrhythmia 26 ( Suppl. ) 156 - 156 2010.4

Enhanced T-wave suppression filterにおける誘発心室細動の検出特性について

久保元基, 西井伸洋, 永瀬聡, 森田宏, 幡芳樹, 中村一文, 草野研吾, 伊藤浩

Journal of Arrhythmia 26 ( Suppl. ) 378 - 378 2010.4

遠隔モニタリングシステムの有用性について

西井伸洋, 久保元基, 中川晃司, 田中正道, 多田毅, 村上正人, 永瀬聡, 中村一文, 幡芳樹, 河野晋久, 森田宏, 草野研吾, 伊藤浩

Journal of Arrhythmia 26 ( Suppl. ) 255 - 255 2010.4

アミオダロン肺障害における臨床的特徴とアンギオテンシン系拮抗薬の効果

二階堂暁, 草野研吾, 中村一文, 多田毅, 三浦綾, 田中正道, 中川晃志, 村上正人, 西井伸洋, 福家聡一郎, 永瀬聡, 森田宏, 伊藤浩, 大江透

Progress in Medicine 30 ( Suppl.1 ) 662 - 666 2010.3

Language：Japanese Publisher：(株)ライフ・サイエンス

アミオダロン肺障害(AIPT)における臨床的特徴とアンギオテンシン系拮抗薬(ASA)の効果について検討した。対象は96例(男性74例、女性22例、平均年齢58.1歳)で、基礎疾患は拡張型心筋症39例、虚血性心疾患26例、肥大型心筋症10例、観察期間は平均33.8ヵ月であった。1)11例(11.5%)にAIPTが認められ、AIPT(+)群ではAIPT(-)群に比し繰り返す心不全のエピソードが有意に多かった。2)ヒト肺胞上皮細胞にアミオダロン添加でアポトーシスは濃度依存性に増加し、アミオダロンにアンギオテンシンII追加でとアポトーシスは有意に増強されたが、アンギオテンシンII受容体拮抗薬添加でアポトーシスは有意に抑制された。3)AIPT(+)群ではAIPT(-)群に比しASA投与量は有意に少なかった。多変量解析では繰り返す心不全エピソードとASA投与量が各々独立したAIPT発症の予測因子であった。

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

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/j.hrthm.2009.10.035

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Relationship between circulating levels of monocyte chemoattractant protein-1 and systolic dysfunction in patients with hypertrophic cardiomyopathy

Jun Iwasaki, Kazufumi Nakamura, Hiromi Matsubara, Yoichi Nakamura, Nobuhiro Nishii, Kimikazu Banba, Masato Murakami, Keiko Ohta-Ogo, Hideo Kimura, Norihisa Toh, Satoshi Nagase, Takefumi Oka, Hiroshi Morita, Kengo Fukushima Kusano, Tohru Ohe

CARDIOVASCULAR PATHOLOGY 18 ( 6 ) 317 - 322 2009.11

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Background: Progression of hypertrophic cardiomyopathy (HCM) to left ventricular dilatation and systolic dysfunction sometimes occurs. However, the mechanism of the transition from hypertrophy to dysfunction has not been elucidated. It has been reported that circulating levels of monocyte chemoattractant protein-1 (MCP-1), which is a major factor promoting the accumulation of macrophages, are increased in patients with congestive heart failure. We measured circulating levels of MCP-1 in patients with HCM and examined whether MCP-1 was expressed in the myocardium of HCM patients. We also examined whether circulating levels of MCP-1 were correlated with left ventricular dysfunction. Methods: Circulating levels of MCP-1 were measured by an enzyme immunoassay in 26 patients with HCM (60 2 years old) and 20 control subjects (57 2 years old). Cardiac function was evaluated by two-dimensional echocardiography and cardiac catheterization. Results: HCM patients had significantly elevated levels of MCP-1 (HCM: 309+/-30 vs. control: 178+/-8 pg/ml, P<001). MCPI levels in patients with systolic dysfunction were significantly higher than those in patients without systolic dysfunction (P<05) and were also significantly higher than those in patients with outflow obstruction (P<05). Immunohistochemical analysis revealed that MCP-1 was expressed in endomyocardial biopsy samples obtained from HCM patients with systolic dysfunction. Furthermore, MCP-1 levels were inversely correlated with fractional shortening (r=-.4011, P<05) and correlated with left ventricular end-diastolic pressure (r=-.579, P<01). Conclusion: These results show that MCP-1 is associated with, and might be involved in the pathogenesis of, left ventricular systolic dysfunction in patients with HCM. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.carpath.2008.12.004

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

Language：English Publishing type：Research paper (scientific journal)

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

心臓サルコイドーシスの新たな展開心サルコイドーシスにおける不整脈の検討

草野研吾, 伴場主一, 高谷陽一, 西井伸洋, 永瀬聡, 中村一文, 森田宏, 伊藤浩, 大江透

日本サルコイドーシス/肉芽腫性疾患学会雑誌 29 ( サプリメント号 ) 23 - 23 2009.10

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

Language：English Publishing type：Research paper (scientific journal)

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

心腔内除細動が心機能に与える影響についての検討

杜徳尚, 西井伸洋, 森田宏, 谷口学, 永瀬聡, 中村一文, 草野研吾, 伊藤浩

日本心臓病学会誌 4 ( Suppl.I ) 226 - 226 2009.8

赤血球容積分布幅(RDW)の非虚血性心疾患患者における予後予測因子としての検討

木島康文, 草野研吾, 福家聡一郎, 西井伸洋, 永瀬聡, 幡芳樹, 中村一文, 森田宏, 伊藤浩

日本心臓病学会誌 4 ( Suppl.I ) 437 - 437 2009.8

非Brugada型特発性心室細動12例の検討

平松茂樹, 森田宏, 中川晃志, 田中正道, 村上正人, 多田毅, 西井伸洋, 永瀬聡, 幡芳樹, 草野研吾

心電図 29 ( Suppl.3 ) S - 380 2009.6

植込み型除細動器植込み術時における除細動閾値テストの心機能に与える影響についての検討

杜徳尚, 西井伸洋, 森田宏, 谷口学, 永瀬聡, 中村一文, 草野研吾

心電図 29 ( Suppl.3 ) S - 405 2009.6

植込み型除細動器を植込まれたBrugada症候群患者における適切作動、不適切作動の検討

西井伸洋, 森田宏, 中川晃司, 田中正道, 平松茂樹, 多田毅, 村上正人, 永瀬聡, 中村一文, 幡芳樹, 草野研吾

心電図 29 ( Suppl.3 ) S - 291 2009.6

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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

心内膜心筋生検において著明な脂肪浸潤を認めたBrugada症候群の1例

田中正道, 多田毅, 村上正人, 平松茂樹, 西井伸洋, 永瀬聡, 幡芳樹, 中村一文, 森田宏, 草野研吾, 由谷親夫

Circulation Journal 73 ( Suppl.II ) 970 - 970 2009.4

ミトコンドリア心筋症にWPW症候群を合併した1例

木島康文, 西井伸洋, 永瀬聡, 幡芳樹, 中村一文, 森田宏, 草野研吾

Circulation Journal 73 ( Suppl.II ) 970 - 970 2009.4

ベラプロストにボセンタンとシルデナフィルを併用し、短期的に著効した重症特発性肺動脈性肺高血圧の2例

福家聡一郎, 川田哲史, 森あい子, 西井伸洋, 永瀬聡, 幡芳樹, 中村一文, 森田宏, 垣下幹夫, 河野晋久, 草野研吾

Circulation Journal 73 ( Suppl.II ) 972 - 972 2009.4

肺動脈の圧排により左冠動脈主幹部に高度の狭窄を認めた心房中隔欠損症、肺高血圧症の1例

尾上豪, 柚木佳, 福家聡一郎, 西井伸洋, 永瀬聡, 幡芳樹, 中村一文, 森田宏, 草野研吾, 赤木禎治, 立野博也

Circulation Journal 73 ( Suppl.II ) 975 - 975 2009.4

進行性完全房室ブロックを認めた若年者の一例

川田哲史, 福家聡一郎, 西井伸洋, 永瀬聡, 幡芳樹, 中村一文, 森田宏, 草野研吾

Circulation Journal 73 ( Suppl.II ) 968 - 968 2009.4

発熱時にBrugada型心電図を合併したWPW症候群の1例

池田悦子, 武田賢治, 西井伸洋, 永瀬聡, 幡芳樹, 中村一文, 森田宏, 草野研吾, 寒川睦子

Circulation Journal 73 ( Suppl.II ) 968 - 968 2009.4

慢性活動性EBウイルス感染症に伴う心筋炎を認めた一症例

田中正道, 中村一文, 川合晴朗, 多田毅, 村上正人, 平松茂樹, 西井伸洋, 永瀬聡, 幡芳樹, 森田宏, 草野研吾, 岩月啓氏, 由谷親夫

循環器科 65 ( 2 ) 219 - 219 2009.2

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

Language：English Publishing type：Research paper (scientific journal)

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

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

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

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

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

Brugada症候群の病態合併不整脈や遺伝子異常について

草野研吾, 森田宏, 永瀬聡, 中村一文, 大江透

心電図 28 ( 5 ) 418 - 418 2008.10

Brugada症候群における心電図パラメーターの経時的変化

中川晃志, 西井伸洋, 永瀬聡, 森田宏, 中村一文, 岡岳文, 大江透, 草野研吾

心電図 28 ( 5 ) 485 - 485 2008.10

ウェーブレット解析によるブルガダ症候群の加算平均心電図の検討

野坂和正, 森田宏, 西井伸洋, 永瀬聡, 中村一文, 岡岳文, 草野研吾, 大江透

心電図 28 ( 5 ) 473 - 473 2008.10

AED(自動体外式除細動器)の有効性と限界

高谷陽一, 西井伸洋, 永瀬聡, 中村一文, 森田宏, 岡岳文, 草野研吾

心電図 28 ( 5 ) 481 - 481 2008.10

Abnormal Atrial Electrophysiological Vulnerability and Structural Atrial Remodeling In High-Risk Patients with Brugada Syndrome: Assessment with Electrophysiology and Echocardiography

Norihisa Toh, Hiroshi Morita, Manabu Taniguchi, Nobuhisa Watanabe, Yasuharu Tanabe, Daiji Miura, Satoshi Nagase, Kazufumi Nakamura, Kengo F. Kusano, Tohru Ohe

CIRCULATION 118 ( 18 ) S775 - S775 2008.10

The QT syndromes: long and short. International journal

Hiroshi Morita, Jiashin Wu, Douglas P Zipes

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

Language：English Publishing type：Research paper (scientific journal)

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.

DOI： 10.1016/S0140-6736(08)61307-0

多発性肺動静脈瘻の一例

野坂和正, 永瀬聡, 中村一文, 森田宏, 武田賢治, 岡岳文, 草野研吾

日本心臓病学会誌 2 ( Suppl.I ) 514 - 514 2008.8

右房内に巨大血栓を認めた一例

森あい子, 川田哲史, 永瀬聡, 中村一文, 森田宏, 武田賢治, 岡岳文, 草野研吾, 大江透, 佐野俊二, 豊永慎二

日本心臓病学会誌 2 ( Suppl.I ) 513 - 513 2008.8

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

Language：English Publishing type：Research paper (scientific journal)

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

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

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

不整脈源性右室心筋症に伴う難治性心室頻拍に対するtotal cavopulumonary connection術後、心不全を繰り返した1例

尾上豪, 福家聡一郎, 宮地晃平, 村上正人, 西井伸洋, 永瀬聡, 中村一文, 森田宏, 岡岳文, 草野研吾, 大江透, 大島祐, 笠原真悟, 佐野俊二

Journal of Arrhythmia 24 ( Suppl. ) 256 - 256 2008.4

心臓再同期療法(CRT)による催不整脈効果の検討

西井伸洋, 草野研吾, 宮地晃平, 平松茂樹, 多田毅, 村上正人, 永瀬聡, 中村一文, 森田宏, 岡岳文, 大江透

Journal of Arrhythmia 24 ( Suppl. ) 151 - 151 2008.4

Brugada症候群の発熱時の心電図変化およびSCN5A変異についての検討

宮地晃平, 森田宏, 多田毅, 平松茂樹, 村上正人, 西井伸洋, 永瀬聡, 中村一文, 草野研吾, 大江透

Journal of Arrhythmia 24 ( Suppl. ) 180 - 180 2008.4

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

Simvastatin Inhibits Proliferation and Migration of Pulmonary Artery Smooth Muscle Cells from Patients with Idiopathic Pulmonary Arterial Hypertension

Miura Daiji, Nakamura Kazufumi, Ikeda Tetsuya, Nagase Satoshi, Morita Hiroshi, Fuke Soichiro, Oka Tekefumi, Mohri Satohi, Kusano Kengo, Matsubara Hiromi, Date Hiroshi, Ohe Tohru

Proceedings of Annual Meeting of the Physiological Society of Japan 2008 189 - 189 2008

Publisher：PHYSIOLOGICAL SOCIETY OF JAPAN

Background: Idiopathic pulmonary arterial hypertension (IPAH) is a progressive disease characterized by inappropriate increase of pulmonary artery smooth muscle cells (PASMCs) leading to occlusion of pulmonary arterioles. In this study, we assessed the inhibitory effects of simvastatin, an HMG-CoA reductase inhibitor, on proliferation and migration of PASMCs obtained from patients with IPAH. Methods and Results: PASMCs were obtained from 6 patients with IPAH who underwent lung transplantation. Platelet-derived growth factor (PDGF) (10 ng/mL) stimulation caused a significantly higher growth rate of PASMCs from patients with IPAH than that of control cells assessed by 3H-thymidine incorporation (P<0.05). Simvastatin at 0.1 μmol/L significantly inhibited PDGF-induced cell proliferation of PASMCs from IPAH patients but did not inhibit proliferation of control cells at the same concentration. Simvastatin at 1 μmol/L also inhibited PDGF-induced migration of PASMCs from IPAH patients assessed by a transwell migration assay (P<0.05) and a time-lapse microscopy assay with a dish that has micro-lithographed squared pattern (Kuraray, Japan) (P<0.0001). Conclusions: Simvastatin may be useful for treatment of patients with IPAH. [J Physiol Sci. 2008;58 Suppl:S189]

DOI： 10.14849/psjproc.2008.0_189_3

Controlled Proliferation of Rat Cardiomyocytes Mediated by Retroviral transfer and Site-specific Recombination

Nakamura Kazufumi, Kobayashi Naoya, Shimizu Juichiro, Miura Daiji, Kono Yasuyuki, Nagase Satoshi, Oka Takefumi, Morita Hiroshi, Kusano Kengo, Ohe Tohru

Proceedings of Annual Meeting of the Physiological Society of Japan 2008 189 - 189 2008

Publisher：PHYSIOLOGICAL SOCIETY OF JAPAN

Background: Cardiomyocytes lose their capacity to proliferate soon after birth. Therefore, we can not obtain large amount of cardiomyocytes in vitro. Here, we report the amplification of the cardiomyocyte population using retrovirus-mediated transfer of simian virus 40 large T (SV40T) antigen. SV40T was subsequently removed by Cre-loxP-based site-specific recombination.Methods and Results: Cultured neonatal rat cardiomyocytes were transduced with a retroviral vector expressing SV40T which is flanked by a pair of loxP recombination targets. Transduced cardiomyocytes yielded clones with greatly extended life spans up to population doubling level 142. Laser scanning cytometry analysis revealed that the transduction caused an induction of cell cycle progression. Complete elimination of the transferred SV40T gene was achieved after infection with a recombinant adenovirus expressing the Cre recombinase. Loss of SV40T caused G1-phase cell cycle arrest and discontinuance of cellular proliferation. DNA microarray analysis of cells that had lost SV40T showed increases in expression levels of cardiomyocyte-specific genes (cardiac actin alpha, Troponin T, myosin light chain and actinin alpha2)Conclusion: This study provides a means to obtain large numbers of well-differentiated and safe cardiomyocytes. [J Physiol Sci. 2008;58 Suppl:S189]

DOI： 10.14849/psjproc.2008.0.189.1

働き盛りの突然死突然あの世に行かないために突然死をきたす不整脈と対策

大江透, 草野研吾, 永瀬聡, 森田宏, 中村一文

日本医学会総会会誌 27回 ( 学術講演要旨 ) 243 - 243 2007.12

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

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

Brugada症候群における右室流出路再分極相のばらつき基礎および臨床的知見

森田宏, 草野研吾, 永瀬聡, 大江透, Zipes Douglas P., Wu Jiashin

心電図 27 ( 5 ) 499 - 499 2007.9

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

Language：English Publishing type：Research paper (scientific journal)

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.

Brugada Syndrome:from gene to bedside Brugada症候群における電気的異常についての検討

草野研吾, 永瀬聡, 森田宏, 中村一文, 伴場主一, 西井伸洋, 大江透

Journal of Cardiology 50 ( Suppl.I ) 133 - 133 2007.8

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

不整脈を合併する輸送欠陥HCN43変異であるD553Nの機能的特性(Functional Characterization of a Trafficking-defective HCN4 Mutation, D553N, Associated with Cardiac Arrhythmia)

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

心電図 25 ( 5 ) 373 - 373 2005.9

[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

Language：Japanese Publishing type：Research paper (scientific journal)

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.

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

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

心室細動に対してキニジンが奏功したBrugada症候群の1例

渡辺敦之, 森田宏, 角田和歌子, 伴場主一, 西井伸洋, 永瀬聡, 中村一文, 齋藤博則, 草野研吾, 江森哲郎, 大江透

Circulation Journal 69 ( Suppl.II ) 797 - 797 2005.4

Brugada syndromeにおけるST上昇の日内変動性の検討 Holter心電図によるST変動測定の可能性

寒川睦子, 中津高明, 渡辺敦之, 豊永慎二, 草地省蔵, 森田宏, 草野研吾, 大江透

心電図 25 ( Suppl.1 ) S - 112 2005.3

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

肺高血圧患者の肺移植前後における心電図変化の検討

藤尾栄起, 森田宏, 松原広己, 宮地克維, 中村一文, 斎藤博則, 草野研吾, 江森哲郎, 大江透

心電図 24 ( 5 ) 368 - 368 2004.8

院内の自動体外式除細動器にて除細動された2症例

斎藤博則, 藤尾栄起, 宮地克維, 中村一文, 森田宏, 草野研吾, 江森哲郎, 大江透, 林峰栄, 氏家良人

心電図 24 ( 5 ) 343 - 343 2004.8

Brugada症候群患者でのイソプレナリンの治療効果

渡辺敦之, 森田宏, 西井伸洋, 伴場主一, 永瀬聡, 中村一文, 斎藤博則, 草野研吾, 江森哲郎, 大江透

心電図 24 ( 5 ) 345 - 345 2004.8

不整脈治療とその効果 QOLと予後の改善をめざして Brugada症候群に対する植込み型除細動器による治療予後とQOLの観点からの検討

江森哲郎, 森田宏, 永瀬聡, 西井伸洋, 伴場主一, 渡辺敦之, 中村一文, 斉藤博則, 草野研吾, 大江透

心電図 24 ( 5 ) 293 - 293 2004.8

非虚血性心筋症患者の生命予後と心室頻拍に対する治療戦略について

西井伸洋, 江森哲郎, 宮地克維, 永瀬聡, 中村一文, 森田宏, 斎藤博則, 草野研吾, 大江透

心電図 24 ( 5 ) 382 - 382 2004.8

不整脈治療とその効果 QOLと予後の改善をめざして Brugada症候群に対する植込み型除細動器による治療予後とQOLの観点からの検討

江森哲郎, 森田宏, 永瀬聡, 西井伸洋, 伴場主一, 渡辺敦之, 中村一文, 斉藤博則, 草野研吾, 大江透

Journal of Cardiology 44 ( Suppl.I ) 194 - 194 2004.8

Brugada症候群に対するキニジンの効果

渡辺敦之, 森田宏, 角田和歌子, 西井伸洋, 伴場主一, 永瀬聡, 中村一文, 斎藤博則, 草野研吾, 江森哲郎, 大江透

心電図 24 ( 5 ) 346 - 346 2004.8

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

右室心尖部以外に留置された植込み型除細動器の心室リードの安全性について

西井伸洋, 森田宏, 渡辺敦之, 伴場主一, 永瀬聡, 斉藤博則, 草野研吾, 江森哲郎, 大江透

不整脈 20 ( 2 ) 215 - 215 2004.4

特発性心室細動と考えられた2症例 Short coupled variant of Torsades de pointesとBrugada症候群との比較検討

渡邊敦之, 森田宏, 伴場主一, 西井伸洋, 永瀬聡, 斉藤博則, 草野研吾, 江森哲郎, 大江透

不整脈 20 ( 2 ) 258 - 258 2004.4

心臓突然死のrisk stratification 非虚血性心筋症患者の生命予後と心室頻拍に対する治療戦略について

西井伸洋, 江森哲郎, 永瀬聡, 森田宏, 斉藤博則, 草野研吾, 大江透

不整脈 20 ( 2 ) 184 - 184 2004.4

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

Two cases of idiopathic ventricular fibrillation: —We weigh the differences between idiopathic ventricular fibrillation and short coupled variant of torsades de pointes—

Watanabe Atsuyuki, Morita Hiroshi, Banba Kimikazu, Nishii Nobuhiro, Nagase Satoshi, Nakamura Kazufumi, Saito Hironori, Kusano Kengo, Emori Tetsuro, Ohe Tohru

Japanese Journal of Electrocardiology 24 ( Suppl4 ) 61 - 67 2004

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

Language：English Publishing type：Research paper (scientific journal)

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.

β遮断薬の酸化ストレス

中村一文, 草野研吾, 森田宏, 斎藤博則, 江森哲郎, 松原広己, 大江透

心電図 23 ( 5 ) 427 - 427 2003.8

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

冠動脈及び全身性血管病変を呈した若年者の一例

大田恵子, 垣下幹夫, 小川愛子, 中村一文, 森田宏, 草野研吾, 江森哲郎, 松原広己, 大江透

血栓と循環 10 ( 3 ) 405 - 405 2002.9

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

Language：English Publishing type：Research paper (scientific journal)

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.

発熱にともないT波交代現象と心室性期外収縮の頻発をきたしたBrugada症候群の一例

原岡佳代, 森田宏, 草野研吾, 永瀬聡, 藤尾英起, 江森哲郎, 大江透

心電図 22 ( 5 ) 482 - 482 2002.8

[Advanced endocardial mapping systems].

Hiroshi Morita, Yasuyuki Kouno, Tohru Ohe

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

Language：Japanese Publishing type：Research paper (scientific journal)

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.

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

Language：English Publishing type：Research paper (scientific journal)

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.

Brugada症候群における心房細動と心房受攻性

森田宏, 永瀬聡, 垣下幹夫, 河野康之, 草野研吾[福島], 江森哲郎, 松原広己, 大江透

不整脈 18 ( 2 ) 241 - 241 2002.4

原発性肺高血圧症における右室心筋内微小血管の検討二次性肺高血圧症と比較して

大田恵子, 中村陽一, 草野研吾, 永瀬聡, 中村一文, 森田宏, 江森哲朗, 松原広己, 大江透

血栓と循環 10 ( 1 ) 85 - 85 2002.3

原発性肺高血圧症における右室心筋内微小血管の検討二次性肺高血圧症と比較して

大田恵子, 中村陽一, 草野研吾, 永瀬聡, 中村一文, 森田宏, 江森哲朗, 松原広己, 大江透

循環器科 51 ( 2 ) 192 - 192 2002.2

Lone AF発症の一要因としてのアデノウイルス心筋炎の可能性

中村陽一, 中村一文, 草野研吾, 大田恵子, 森田宏, 江森哲郎, 松原広巳, 大江透, 山田雅夫

循環器科 51 ( 2 ) 197 - 197 2002.2

原発性肺高血圧症における右室心筋内微小血管の組織学的検討

大田恵子, 草野研吾, 永瀬聡, 宮地克維, 中村一文, 森田宏, 江森哲郎, 松原広己, 大江透, 中村陽一

Japanese Circulation Journal 65 ( Suppl.III ) 798 - 798 2001.10

Brugada症候群と類似疾患の病態有症候群から無症候群まで Brugada様心電図症例の階層化について

森田宏, 永瀬聡, 久松研一, 藤尾英起, 小林誠, 竹中志保, 草野研吾, 江森哲郎, 松原広己, 大江透

心電図 21 ( 5 ) 610 - 610 2001.9

不安定狭心症を合併しTorsades de pointesが頻発した先天性QT延長症候群の一例

原岡佳代, 森田宏, 藤尾栄起, 草野研吾, 江森哲郎, 松原広己, 大江透, 大林直嗣

心電図 21 ( 5 ) 718 - 718 2001.9

心電図上,著明なQT延長ならびにT波の交代現象を示した原発性副甲状腺機能低下症の1例

藤尾栄起, 森田宏, 岩崎淳, 原岡佳代, 谷義則, 橋本克史, 宮地克維, 江森哲郎, 草野研吾, 徳永常登

心電図 21 ( 5 ) 704 - 704 2001.9

Arrhythmic Stormを起こした植込み型除細動器植込み患者の臨床的特徴

江森哲郎, 草野研吾, 森田宏, 松原広巳, 佐野俊二, 大江透

心電図 21 ( 5 ) 640 - 640 2001.9

致死性不整脈の検出と予知 Brugada症候群の不整脈の予知症候性と無症候性患者でのアプローチ

森田宏, 永瀬聡, 藤尾栄起, 原岡佳代, 久松研一, 森田志保, 草野研吾, 江森哲郎, 松原広己, 大江透

心電図 21 ( 5 ) 589 - 589 2001.9

Brugada症候群の心室性不整脈の発生部位

森田宏, 永瀬聡, 久松研一, 垣下幹夫, 中村一文, 森田志保[竹中], 草野研吾, 江森哲郎, 松原広己, 大江透

心電図 21 ( 5 ) 637 - 637 2001.9

心筋症患者の心筋からのアデノウイルスの検出

中村一文, 草野研吾, 中村陽一, 大田恵子, 永瀬聡, 宮地克維, 森田宏, 江森哲郎, 松原広己, 大江透

Journal of Cardiology 38 ( Suppl.I ) 183 - 183 2001.8

末梢性肺動脈狭窄による肺高血圧症の一例

大田恵子, 中村陽一, 広瀬英軌, 永瀬聡, 宮地克維, 中村一文, 森田宏, 草野研吾, 江森哲郎, 松原広己

Journal of Cardiology 38 ( Suppl.I ) 244 - 244 2001.8

原発性肺高血圧症患者へのプロスタサイクリン持続静注療法導入時における血行動態破綻の予測因子の検討

宮地克維, 松原広己, 永瀬聡, 中村一文, 森田宏, 草野研吾, 江森哲郎, 大江透

Journal of Cardiology 38 ( Suppl.I ) 303 - 303 2001.8

不整脈新世紀難治性不整脈治療への挑戦 Brugada症候群患者へのアプローチ

森田宏, 永瀬聡, 久松研一, 垣下幹夫, 森田志保[竹中], 中村一文, 草野研吾, 江森哲郎, 松原広己, 大江透

Journal of Cardiology 38 ( Suppl.I ) 81 - 81 2001.8

体表面心電図と第三肋間の心電図記録によるBrugada様心電図を示す無症候例の検討 Brugada症候群との比較

久松研一, 草野研吾, 森田宏, 竹中志保, 大田恵子, 永瀬聡, 中村一文, 松原広己, 江森哲郎, 大江透

不整脈 17 ( 2 ) 273 - 273 2001.4

植込み型除細動器植込み患者の臨床経過とQOLについて

江森哲郎, 草野研吾, 森田宏, 松原広己, 大江透, 佐野俊二

不整脈 17 ( 2 ) 284 - 284 2001.4

カテーテルアブレーションが著効した多形性心室頻拍の1例

森田宏, 草野研吾[福島], 中村一文, 藤本良久, 山本美香, 小林誠, 永瀬聡, 垣下幹夫, 江森哲朗, 山成洋, 大江透

心臓 32 ( Suppl.5 ) 17 - 20 2000.12

Language：Japanese Publisher：(公財)日本心臓財団

65歳女.発作時の心電図で多形性心室頻拍から心室細動への移行がみられた.安静時心電図は明らかな異常を認めず,各種画像検査で器質的心疾患は認められなかった.植込み型除細動器(ICD)とDisopyramideの投与を開始したが,退院3ヵ月目に頻回のICD作動が生じ,ICDの保存記録で反復する多形性心室頻拍のshort runを認め,電気生理学的検査を施行した.PVTは常に右室流出路起源の心室期外収縮(PVC)から発生し,心室性期外収縮の起源近くからの頻回刺激(220/分)にて多形性心室頻拍と同様のQRS波形の変化を認めた.以上から,この多形性心室頻拍の起源は一つで,心室性期外収縮の延長上に多形性心室頻拍があると考えられた為,先行する多形性心室頻拍をtargetとしてカテーテルアブレーションを行った.以後約2年の経過でICDの作動なく経過している

RF信号を用いた高安動脈炎の組織診断の試み

中村陽一, 山成洋, 松原広己, 草野研吾, 森田宏, 坪根泉, 由谷親夫, 大江透

血栓と循環 8 ( 3 ) 275 - 275 2000.9

心房頻拍との鑑別が困難であった非通常型房室結節回帰性頻拍の1例

永瀬聡, 草野研吾, 藤本良久, 森田宏, 松原広己, 大江透

心電図 20 ( 5 ) 495 - 495 2000.8

体表面電位図を用いた心房粗動興奮伝播の検討

森田宏, 草野研吾, 藤本良久, 久松研一, 永瀬聡, 竹中志保, 山成洋, 大江透

心電図 20 ( 5 ) 502 - 502 2000.8

至適通電部位が冠動脈尖であった心室頻拍の3症例

永瀬聡, 草野研吾, 森田宏, 藤本良久, 大田恵子, 山本美香, 松原広己, 大江透

心電図 20 ( 5 ) 486 - 486 2000.8

体表面心電図によるBrugada様心電図を呈する,無症候例の検討 Brugada症候群との比較

久松研一, 草野研吾, 森田宏, 竹中志保, 永瀬聡, 山成洋, 大江透

心電図 20 ( 5 ) 502 - 502 2000.8

12誘導心電図による流出路起源心室頻拍の至適アブレーション部位の推定 pacemappingを用いた検討

草野研吾, 藤本良久, 森田宏, 永瀬聡, 大江透

心電図 20 ( 5 ) 487 - 487 2000.8

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

Language：English Publisher：Japanese Circulation Society

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

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

カテーテルアブレーション後,右室内にExit Blockを生じた不整脈源性右室異形成症の1例

草野研吾, 森田宏, 江森哲郎, 垣下幹夫, 物部秀明, 藤本良久, 伴場主一, 谷山真規子, 中山和昭, 松原広己, 山成洋, 大江透

臨床心臓電気生理 23 113 - 120 2000.5

Language：Japanese Publisher：臨床心臓電気生理研究会

46歳女.以前より不整脈源性右室異形成症としてfollowされており,昼食後に突然動悸が出現した.心室頻拍(VT)は190/分で,電気生理学的検査では,右室のbaseから心尖部の下壁の広い範囲に,心電図上のイプシロン波に一致する大きなdelayed potential(DP)を伴う異常電位が認められた.このDPの認められる部位からのペーシングによって全てVTとほぼ同波形のQRS波形が得られた.VTに対するアブレーションは回路のexit siteに近いと考えられたmid free wallの通電によって行い,以後誘発不能となった.その後,DPの記録される部位からペーシングを行ったところ,ペーシングによってDPは捕捉されたが,体表面心電図のQRS波とは解離を示した

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

Language：English Publisher：PHYSIOLOGICAL SOCIETY OF JAPAN

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

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

無症候性Brugada型心電図波形を呈する症例についての検討

大田恵子, 竹中志保, 永瀬聡, 森田宏, 草野研吾, 松原広己, 山成洋, 大江透

日本内科学会雑誌 89 ( 臨増 ) 126 - 126 2000.2

Successful catheter ablation in a patient with polymorphic ventricular tachycardia

Kengo Fukushima Kusano, Mika Yamamoto, Tetsuro Emori, Hiroshi Morita, Tohru Ohe

Journal of Cardiovascular Electrophysiology 11 ( 6 ) 682 - 685 2000

Language：English Publishing type：Research paper (scientific journal) Publisher：Futura Publishing Company Inc.

We describe a patient with polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF) without organic heart disease who was cured by radiofrequency catheter ablation. The patient was a 65-year-old woman with a 10-year history of recurrent syncope. There was no evidence of organic heart disease, and the QT interval during sinus rhythm was borderline normal (corrected QT interval = 0.45 sec(1/2)). ECG recording during syncope showed PVT. On one occasion, PVT degenerated into VF. This PVT was always induced by a premature ventricular complex (PVC) originating from the right ventricular (RV) outflow tract. Rapid pacing (220 beats/min) at the site of PVC origin reproduced polymorphic change of the QRS wave on surface ECG that was similar to PVT. This suggests that the PVT originated from a single focus in the RV outflow tract. Catheter ablation was performed at the site of PVC origin. During 18-month follow-up, PVT/VF was not documented.

DOI： 10.1111/j.1540-8167.2000.tb00031.x

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

類似したwide QRS tachycardia波形を認めた特殊な頻拍の2症例

森田宏, 福島研吾[草野], 藤本良久, 垣下幹夫, 江森哲朗, 山成洋, 大江透

心電図 19 ( 5 ) 610 - 610 1999.8

心室再分極過程alternans現象に及ぼすNicorandilの影響動物実験及び臨床例からの検討

藤本良久, 草野研吾, 森田宏, 垣下幹夫, 山成洋, 大江透

心電図 19 ( 5 ) 529 - 529 1999.8

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

Language：English Publisher：Japanese Circulation Society

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

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

Early Afterdepolarization Abolished by Potassium Channel Opener in a Patient with Idiopathic Long QT Syndrome

TETSUYA SATO, YOSHIKI HATA, MIKA YAMAMOTO, HIROSHI MORITA, KOZO MIZUO, HIROSHI YAMANARI, DAIJI SAITO, TOHRU OHE

Journal of Cardiovascular Electrophysiology 6 ( 4 ) 279 - 282 1995

Language：English Publishing type：Research paper (scientific journal)

Abolished Early Afterdepolarization by Nicorandil. We describe a 17‐year‐old boy with idiopathic long QT syndrome and repeated syncopal episodes. Early afterdepolarization (EAD) in the monophasic action potential (MAP) was demonstrated in the posterior septum of the left ventricle. Injection of the potassium channel opener nicorandil decreased KAD and shortened MAP duration. The syncopal episodes due to ventricular fibrillation disappeared after administration of the potassium channel opener. Copyright © 1995, Wiley Blackwell. All rights reserved

DOI： 10.1111/j.1540-8167.1995.tb00400.x

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