Faculty Profiles - NAKAMURA Kazufumi

iPSC-Derived Biological Pacemaker—From Bench to Bedside Reviewed

Quan Duy Vo, Kazufumi Nakamura, Yukihiro Saito, Toshihiro Iida, Masashi Yoshida, Naofumi Amioka, Satoshi Akagi, Toru Miyoshi, Shinsuke Yuasa

Cells 13 ( 24 ) 2045 - 2045 2024.12

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Induced pluripotent stem cell (iPSC)-derived biological pacemakers have emerged as an alternative to traditional electronic pacemakers for managing cardiac arrhythmias. While effective, electronic pacemakers face challenges such as device failure, lead complications, and surgical risks, particularly in children. iPSC-derived pacemakers offer a promising solution by mimicking the sinoatrial node’s natural pacemaking function, providing a more physiological approach to rhythm control. These cells can differentiate into cardiomyocytes capable of autonomous electrical activity, integrating into heart tissue. However, challenges such as achieving cellular maturity, long-term functionality, and immune response remain significant barriers to clinical translation. Future research should focus on refining gene-editing techniques, optimizing differentiation, and developing scalable production processes to enhance the safety and effectiveness of these biological pacemakers. With further advancements, iPSC-derived pacemakers could offer a patient-specific, durable alternative for cardiac rhythm management. This review discusses key advancements in differentiation protocols and preclinical studies, demonstrating their potential in treating dysrhythmias.

DOI： 10.3390/cells13242045

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

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

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

The American Journal of Cardiology 2024.12

Crescent-Shaped Atrial Septal Defect: A New Clinical Entity of an Acquired Defect for Transcatheter Closure. International journal

Mitsutaka Nakashima, Teiji Akagi, Yoichi Takaya, Takashi Miki, Rie Nakayama, Koji Nakagawa, Norihisa Toh, Kazufumi Nakamura, Shinsuke Yuasa

JACC. Asia 4 ( 12 ) 1013 - 1016 2024.12

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

Clinical and Histopathological Characteristics of Patients With Myocarditis After mRNA COVID-19 Vaccination Reviewed

Taku Omori, Kazuaki Maruyama, Keiko Ohta-Ogo, Kinta Hatakeyama, Hatsue Ishibashi-Ueda, Kenji Onoue, Toshiyuki Nagai, Seiya Kato, Takahiro Okumura, Masayoshi Oikawa, Eisuke Amiya, Saeko Yoshizawa, Tadaki Suzuki, Hidemasa Goto, Kazufumi Nakamura, Takeo Fujino, Keishi Moriwaki, Shiro Nakamori, Toshihisa Anzai, Yasushi Sakata, Michiaki Hiroe, Kyoko Imanaka-Yoshida, Kaoru Dohi

Circulation Journal 2024.11

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

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

Morphological Features of Patent Foramen Ovale Compared Between Older and Young Patients With Cryptogenic Ischemic Stroke Reviewed

Mitsutaka Nakashima, Yoichi Takaya, Rie Nakayama, Masahiro Tsuji, Teiji Akagi, Takashi Miki, Kazufumi Nakamura, Shinsuke Yuasa

Circulation Journal 88 ( 9 ) 1398 - 1405 2024.8

Prognostic value of right atrial function in patients with significant tricuspid regurgitation Reviewed

Takahiro Nishihara, Yoichi Takaya, Rie Nakayama, Yu Yoshida, Norihisa Toh, Toru Miyoshi, Kazufumi Nakamura, Shinsuke Yuasa

ESC Heart Failure 11 ( 6 ) 4019 - 4027 2024.8

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

Abstract

Aims

Although right ventricular (RV) dysfunction is associated with adverse outcomes in tricuspid regurgitation (TR), the potential role of right atrial (RA) function is unknown. We aimed to investigate the relationship between RA function and clinical outcomes in patients with significant TR.

Methods

This retrospective study included 169 outpatients with moderate or severe TR due to left‐sided heart diseases who underwent transthoracic echocardiography between June 2020 and April 2023 (average age, 75 ± 10 years; male, 40%). Patients with atrial fibrillation were excluded from this study due to the inaccuracy of the evaluation using 2D speckle‐tracking echocardiography. RA function was compared between patients with and without events, which were defined as all‐cause mortality or hospitalization due to heart failure. RA function was calculated as RA global longitudinal strain (RAGLS) with the 2D speckle‐tracking echocardiography.

Results

During a median follow‐up of 13 months, 19 patients had events (all‐cause mortality: 14 cases, hospitalization due to heart failure: 5 cases). RAGLS was lower in patients with events than in those without events (13% ± 10% vs. 18% ± 9%, P = 0.02). When the patients were categorized into two groups [low RAGLS ≤ 16.2% vs. high RAGLS > 16.2%, high RA volume index (RAVI) ≥ 50 mL/m² vs. low RAVI < 50 mL/m²], Kaplan–Meier curves showed that patients with low RAGLS had higher event rates than those with high RAGLS (log‐rank test, P = 0.003). Patients with high RAVI had higher event rates than those with low RAVI (log‐rank test, P < 0.001). In the multivariate Cox regression analysis, low RAGLS (≤16.2%) was significantly associated with events in a model that included RV dysfunction (RV fractional area change ≤ 35%) or high RAVI (≥50 mL/m²) (hazard ratio: 4.55, 95% confidence interval: 1.51–13.71, P < 0.01; hazard ratio: 4.57, 95% confidence interval: 1.52–13.79, P < 0.01, respectively).

Conclusions

RAGLS is associated with all‐cause mortality and hospitalization due to heart failure in patients with significant TR. Our results suggest that RA function is a sensitive marker for identifying the risk stratification of significant TR.

DOI： 10.1002/ehf2.14846

Fenestrated GORE® CARDIOFORM ASD occluder for transcatheter atrial septal defect closure in a geriatric patient. Reviewed

Mitsutaka Nakashima, Teiji Akagi, Takashi Miki, Rie Nakayama, Yoichi Takaya, Koji Nakagawa, Satoshi Akagi, Norihisa Toh, Kazufumi Nakamura

Journal of cardiology cases 30 ( 2 ) 31 - 34 2024.8

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

UNLABELLED: An 82-year-old man with a secundum atrial septal defect (ASD) underwent transcatheter closure. The patient had a wide area of aortic and superior rim deficiency, with left ventricular diastolic dysfunction and moderate mitral regurgitation. These findings suggested the risk of both cardiac erosion and increased left atrial pressure after closure. To avoid cardiac erosion, a GORE® CARDIOFORM ASD (GCA) occluder (W.L. Gore & Associates, Flagstaff, AZ, USA) was considered an appropriate device in this patient. However, the possibility of excessively high left atrial pressure due to complete defect closure was a concern. Thus, we created a 4.5-mm fenestration using a surgical punch in the fabric membrane of a 44-mm GCA. The device was deployed in an appropriate position, and no significant elevation of pulmonary capillary wedge pressure was observed. One month after the closure, marked improvement in clinical symptoms and continuous flow through the fenestration were observed. This novel fenestration technique may contribute to expansion of the indications for transcatheter ASD closure in patients who require a GCA owing to an anatomically high risk of erosion accompanied by left ventricular diastolic dysfunction. LEARNING OBJECTIVE: In elderly patients with left ventricular diastolic dysfunction, transcatheter atrial septal defect (ASD) closure is difficult because rapid resolution of an ASD shunt can cause an increase in left atrial pressure. Previous reports described the creation of a fenestration in the closure device. The use of a GORE® CARDIOFORM ASD (GCA) occluder can reduce the erosion risk; however, creating a stable fenestration is difficult. We developed a novel technique to create a stable fenestration in a GCA.

DOI： 10.1016/j.jccase.2024.04.001

Reply to the letter, “Residual shunt after patent foramen ovale closure: The devil is in the details!” regarding article “Relationship between patent foramen ovale anatomical features and residual shunt after patent foramen ovale closure” Reviewed

Rie Nakayama, Yoichi Takaya, Teiji Akagi, Rika Takemoto, Madoka Haruna, Mitsutaka Nakashima, Takashi Miki, Koji Nakagawa, Norihisa Toh, Kazufumi Nakamura, Shinsuke Yuasa

Catheterization and Cardiovascular Interventions 104 ( 3 ) 633 - 634 2024.7

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

Prognostic Implications of Insulin Resistance in Heart Failure in Japan Reviewed

Keiichiro Iwasaki, Kazufumi Nakamura, Satoshi Akagi, Yoichi Takaya, Hironobu Toda, Toru Miyoshi, Shinsuke Yuasa

Nutrients 16 ( 12 ) 1888 - 1888 2024.6

Authorship：Corresponding author Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Diabetes mellitus (DM) is a major risk and prognostic factor for heart failure (HF). Insulin resistance (IR) is an important component of DM, but the relationship between IR and HF prognosis has not yet been established across a wide variety of HF populations. We retrospectively evaluated the relationship between IR and clinical outcomes of HF patients at our hospital between 2017 and 2021. IR was defined as a homeostatic model assessment of IR (HOMA-IR) index ≥ 2.5, calculated from fasting blood glucose and insulin concentrations. The primary outcome was a composite of all-cause death and hospitalisation for HF (HHF). Among 682 patients included in the analyses, 337 (49.4%) had IR. The median age was 70 [interquartile range (IQR): 59–77] years old, and 66% of the patients were men. Among the patients, 41% had a left ventricular ejection fraction below 40%, and 32% had DM. The median follow-up period was 16.5 [IQR: 4.4–37.3] months. IR was independently associated with the primary outcome (HR: 1.91, 95% CI: 1.39–2.62, p < 0.0001), death (hazard ratio [HR]: 1.86, 95% confidence interval [CI]: 1.28–2.83, p < 0.01), and HHF (HR: 1.91, 95% CI: 1.28–2.83, p < 0.01). HOMA-IR is an independent prognostic factor of HF in a wide variety of HF populations.

DOI： 10.3390/nu16121888

The use of artificial intelligence in induced pluripotent stem cell-based technology over 10-year period: A systematic scoping review Reviewed

Quan Duy Vo, Yukihiro Saito, Toshihiro Ida, Kazufumi Nakamura, Shinsuke Yuasa

PLOS ONE 19 ( 5 ) e0302537 - e0302537 2024.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Public Library of Science (PLoS)

Background

Stem cell research, particularly in the domain of induced pluripotent stem cell (iPSC) technology, has shown significant progress. The integration of artificial intelligence (AI), especially machine learning (ML) and deep learning (DL), has played a pivotal role in refining iPSC classification, monitoring cell functionality, and conducting genetic analysis. These enhancements are broadening the applications of iPSC technology in disease modelling, drug screening, and regenerative medicine. This review aims to explore the role of AI in the advancement of iPSC research.

Methods

In December 2023, data were collected from three electronic databases (PubMed, Web of Science, and Science Direct) to investigate the application of AI technology in iPSC processing.

Results

This systematic scoping review encompassed 79 studies that met the inclusion criteria. The number of research studies in this area has increased over time, with the United States emerging as a leading contributor in this field. AI technologies have been diversely applied in iPSC technology, encompassing the classification of cell types, assessment of disease-specific phenotypes in iPSC-derived cells, and the facilitation of drug screening using iPSC. The precision of AI methodologies has improved significantly in recent years, creating a foundation for future advancements in iPSC-based technologies.

Conclusions

Our review offers insights into the role of AI in regenerative and personalized medicine, highlighting both challenges and opportunities. Although still in its early stages, AI technologies show significant promise in advancing our understanding of disease progression and development, paving the way for future clinical applications.

DOI： 10.1371/journal.pone.0302537

Association Between Aortic Valve Calcification and Severity of Concomitant Aortic Regurgitation in Patients With Severe Aortic Stenosis. Reviewed

Fumi Yokohama, Yoichi Takaya, Keishi Ichikawa, Rie Nakayama, Takashi Miki, Hironobu Toda, Norihisa Toh, Toru Miyoshi, Kazufumi Nakamura, Hiroshi Ito

Circulation journal : official journal of the Japanese Circulation Society 2024.4

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

BACKGROUND: Patients with severe aortic stenosis (AS) frequently have concomitant aortic regurgitation (AR), but the association between aortic valvular calcification (AVC) and the severity of AR remains unclear.Methods and Results: We retrospectively reviewed patients with severe AS who underwent transthoracic echocardiography and multidetector computed tomography (MDCT) within 1 month. The patients were divided into 3 groups according to the degree of concomitant AR. The association between AVC and the severity of concomitant AR was assessed in patients with severe AS. The study population consisted of 95 patients: 43 men and 52 women with a mean age of 82±7 years. Of the 95 patients with severe AS, 27 had no or trivial AR, 53 had mild AR, and 15 had moderate AR. The AVC score (AVCS) and AVC volume (AVCV) significantly increased as the severity of concomitant AR increased (P=0.014 for both), and similar findings were obtained for the AVCS and AVCV indexes (P=0.004 for both). CONCLUSIONS: The severity of AR correlated with AVCS and AVCV measured by MDCT in patients with severe AS. AVC may cause concomitant AR, leading to worsening of disease condition.

DOI： 10.1253/circj.CJ-22-0746

Artificial intelligence to detect noise events in remote monitoring data Reviewed

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

Feasibility of Treat and Repair Strategy in Congenital Heart Defects With Pulmonary Arterial Hypertension. Reviewed International journal

Satoshi Akagi, Shingo Kasahara, Teiji Akagi, Kentaro Ejiri, Toshiharu Mitsuhashi, Koji Nakagawa, Kazufumi Nakamura, Hiroshi Ito

JACC. Advances 3 ( 4 ) 100887 - 100887 2024.4

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

BACKGROUND: A treatment strategy for congenital heart defects with moderate to severe pulmonary arterial hypertension (PAH) has not been established. OBJECTIVES: The purpose of this study was to identify patients in whom a treat and repair strategy was considered and to examine pretreatment variables associated with successful defect repair. METHODS: Patients with atrial or ventricular septal defect and PAH (pulmonary vascular resistance [PVR] ≥ 5 Wood units) eligible for the treat and repair strategy were included. Hemodynamics among pretreatment, pre-repair, and post-defect repair were compared. Clinical outcomes in patients with or without defect repair were also compared. Clinical outcomes included all-cause death, hospitalization for worsening pulmonary hypertension, and lung transplantation. RESULTS: Among 25 eligible for the treat and repair strategy, 20 underwent successful repair (repaired group) and 5 did not have a repair (unrepaired group). In the repaired group, PVR significantly decreased from 9.6 ± 2.6 WU at pretreatment to 5.0 ± 3.4 pre-repair (ß coefficient -4.6 [95% CI: -5.9 to -3.3]). The pulmonary to systemic blood flow ratio (Qp/Qs) increased from 1.5 ± 0.6 at pretreatment to 2.4 ± 1.3 pre-repair (ß coefficient 0.9 [95% CI: 0.4-1.38]). In the unrepaired group, pretreatment PVR decreased with treatment; however, PVR remained elevated. Qp/Qs did not change between pretreatment and post-treatment. The repaired group had a better prognosis than the unrepaired group (HR 0.092 [95% CI: 0.009-0.905]). Pretreatment mean pulmonary artery pressure, PVR, Qp/Qs, and arterial oxygen saturations were associated with undergoing defect repair. CONCLUSIONS: In this small cohort, a treat and repair strategy was successfully used in a significant proportion of the patients with congenital heart defects with moderate to severe PAH.

DOI： 10.1016/j.jacadv.2024.100887

Diagnostic improvements of calcium-removal image reconstruction algorithm using photon-counting detector CT for calcified coronary lesions Reviewed

Takahiro Nishihara, Toru Miyoshi, Mitsutaka Nakashima, Noriaki Akagi, Yusuke Morimitsu, Tomohiro Inoue, Takashi Miki, Masatoki Yoshida, Hironobu Toda, Kazufumi Nakamura, Shinsuke Yuasa

European Journal of Radiology 172 111354 - 111354 2024.3

先天性心疾患患者の移行期医療:成人循環器医の協力を得る方策成人先天性心疾患の診療の手助けとなる心エコー図検査

武本梨佳, 杜徳尚, 高谷陽一, 中山理絵, 赤木禎治, 中村一文, 笠原真悟, 大塚文男

日本循環器学会学術集会抄録集 88回 CS3 - 4 2024.3

Significant delayed conduction and characteristic ventricular tachycardias in patients with cardiac sarcoidosis and electrical storm. Reviewed 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 2024.2

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

Relationship between patent foramen ovale anatomical features and residual shunt after patent foramen ovale closure Reviewed

Catheter-directed thrombolysis for critical hand ischemia with failed distal venous arterialization. Reviewed

Mitsutaka Nakashima, Hironobu Toda, Kentaro Ejiri, Susumu Ozawa, Satoshi Akagi, Kazufumi Nakamura

Cardiovascular intervention and therapeutics 2024.1

Rie Nakayama, Yoichi Takaya, Teiji Akagi, Rika Takemoto, Madoka Haruna, Mitsutaka Nakashima, Takashi Miki, Koji Nakagawa, Norihisa Toh, Kazufumi Nakamura

Cardiovascular Intervention and Therapeutics 39 ( 2 ) 200 - 206 2024.1

Induced Pluripotent Stem Cell-Derived Cardiomyocytes Therapy for Ischemic Heart Disease in Animal Model: A Meta-Analysis Reviewed

Quan Duy Vo, Yukihiro Saito, Kazufumi Nakamura, Toshihiro Iida, Shinsuke Yuasa

International Journal of Molecular Sciences 25 ( 2 ) 987 - 987 2024.1

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Ischemic heart disease (IHD) poses a significant challenge in cardiovascular health, with current treatments showing limited success. Induced pluripotent derived–cardiomyocyte (iPSC-CM) therapy within regenerative medicine offers potential for IHD patients, although its clinical impacts remain uncertain. This study utilizes meta-analysis to assess iPSC-CM outcomes in terms of efficacy and safety in IHD animal model studies. A meta-analysis encompassing PUBMED, ScienceDirect, Web of Science, and the Cochrane Library databases, from inception until October 2023, investigated iPSC therapy effects on cardiac function and safety outcomes. Among 51 eligible studies involving 1012 animals, despite substantial heterogeneity, the iPSC-CM transplantation improved left ventricular ejection fraction (LVEF) by 8.23% (95% CI, 7.15 to 9.32%; p < 0.001) compared to control groups. Additionally, cell-based treatment reduced the left ventricle fibrosis area and showed a tendency to reduce left ventricular end-systolic volume (LVESV) and end-diastolic volume (LVEDV). No significant differences emerged in mortality and arrhythmia risk between iPSC-CM treatment and control groups. In conclusion, this meta-analysis indicates iPSC-CM therapy’s promise as a safe and beneficial intervention for enhancing heart function in IHD. However, due to observed heterogeneity, the efficacy of this treatment must be further explored through large randomized controlled trials based on rigorous research design.

DOI： 10.3390/ijms25020987

In vivo tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging Reviewed

Corrigendum: Use of the index of pulmonary vascular disease for predicting longterm outcome of pulmonary arterial hypertension associated with congenital heart disease. Reviewed International journal

Ayako Chida-Nagai, Naoki Masaki, Kay Maeda, Konosuke Sasaki, Hiroki Sato, Jun Muneuchi, Yoshie Ochiai, Hiroomi Murayama, Masahiro Tahara, Atsuko Shiono, Atsushi Shinozuka, Fumihiko Kono, Daisuke Machida, Shinichi Toyooka, Seiichiro Sugimoto, Kazufumi Nakamura, Satoshi Akagi, Maiko Kondo, Shingo Kasahara, Yasuhiro Kotani, Junichi Koizumi, Katsuhiko Oda, Masako Harada, Daisuke Nakajima, Akira Murata, Hazumu Nagata, Koichi Yatsunami, Tomio Kobayashi, Yoshikiyo Matsunaga, Takahiro Inoue, Hiroyuki Yamagishi, Naomi Nakagawa, Katsuki Ohtani, Masaki Yamamoto, Yushi Ito, Tatsunori Hokosaki, Yuta Kuwahara, Satoshi Masutani, Koji Nomura, Tsutomu Wada, Hirofumi Sawada, Masayuki Abiko, Tatsunori Takahashi, Yuichi Ishikawa, Seigo Okada, Atsushi Naitoh, Takako Toda, Tatsuya Ando, Akihiro Masuzawa, Shinsuke Hoshino, Masaaki Kawada, Yuichi Nomura, Kentaro Ueno, Naoki Ohashi, Tsuyoshi Tachibana, Yuchen Cao, Hideaki Ueda, Sadamitsu Yanagi, Masaaki Koide, Norie Mitsushita, Kouji Higashi, Yoshihiro Minosaki, Tomohiro Hayashi, Takashi Okamoto, Kenji Kuraishi, Eiji Ehara, Hidekazu Ishida, Hitoshi Horigome, Takashi Murakami, Kohta Takei, Taku Ishii, Gen Harada, Yasutaka Hirata, Jun Maeda, Shunsuke Tatebe, Chiharu Ota, Yasunobu Hayabuchi, Hisanori Sakazaki, Takashi Sasaki, Keiichi Hirono, Sayo Suzuki, Masahiro Yasuda, Atsuhito Takeda, Madoka Sawada, Kagami Miyaji, Atsushi Kitagawa, Yosuke Nakai, Nobuyuki Kakimoto, Kouta Agematsu, Atsushi Manabe, Yoshikatsu Saiki

Frontiers in cardiovascular medicine 11 1369831 - 1369831 2024

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

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

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

Utility of angiopoietin-2 measured early after the Fontan operation Reviewed

Norihisa Toh, Teiji Akagi, Kazufumi Nakamura, Shingo Kasahara

The American Journal of Cardiology 205 516 - 516 2023.10

Yukihiro Saito, Naoko Nose, Toshihiro Iida, Kaoru Akazawa, Takayuki Kanno, Yuki Fujimoto, Takanori Sasaki, Masaru Akehi, Takahiro Higuchi, Satoshi Akagi, Masashi Yoshida, Toru Miyoshi, Hiroshi Ito, Kazufumi Nakamura

Frontiers in Cardiovascular Medicine 10 2023.9

Authorship：Last author Language：English Publishing type：Research paper (scientific journal) Publisher：Frontiers Media SA

Introduction

Transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established.

Methods

In this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as ¹²⁵I, ¹⁸F-tetrafluoroborate (TFB), and ^99mTc-pertechnetate (^99mTcO₄⁻), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs.

Results

To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by ^99mTcO₄⁻ single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of ¹²⁵I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using ^99mTcO₄⁻ SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells.

Discussion

Such functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions.

DOI： 10.3389/fcvm.2023.1261330

Evidence for Hypoxia-Induced Shift in ATP Production from Glycolysis to Mitochondrial Respiration in Pulmonary Artery Smooth Muscle Cells in Pulmonary Arterial Hypertension. Reviewed International journal

Satoshi Akagi, Kazufumi Nakamura, Megumi Kondo, Satoshi Hirohata, Heiichiro Udono, Mikako Nishida, Yukihiro Saito, Masashi Yoshida, Toru Miyoshi, Hiroshi Ito

Journal of clinical medicine 12 ( 15 ) 2023.7

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

BACKGROUND: The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. METHODS: We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology. RESULTS: Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 ± 5 pmol/min) than in non-PAH-PASMCs (70 ± 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 ± 5 pmol/min) than in non-PAH-PASMCs (14 ± 3 pmol/min) under hypoxia. CONCLUSIONS: There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia.

DOI： 10.3390/jcm12155028

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

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

Authorship：Corresponding author 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

Impact of malnutrition on prognosis in patients with pulmonary arterial hypertension. Reviewed International journal

Mitsutaka Nakashima, Satoshi Akagi, Kentaro Ejiri, Kazufumi Nakamura, Hiroshi Ito

Pulmonary circulation 13 ( 3 ) e12286 - 3 2023.7

Language：English Publishing type：Research paper (scientific journal) Publisher：(一社)日本循環器学会

Pulmonary arterial hypertension is a life-threatening disease that coexists with right heart failure. We evaluated the relationship between malnutrition and prognosis in patients with pulmonary arterial hypertension, as malnutrition is known as a prognosis determinant in chronic heart failure. We retrospectively reviewed data of patients with pulmonary arterial hypertension before treatment. The Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Controlling Nutritional Status scores on the day of diagnosis were calculated to assess the nutritional status. Clinical endpoints were defined as composite outcomes of all-cause death or lung transplantation. Eighty patients were enrolled (mean age, 50 years; 23 men). The mean pulmonary arterial pressure was 47 ± 19 mmHg, Geriatric Nutritional Risk Index was 99.9 ± 12.0, and Prognostic Nutritional Index was 46.3 ± 10.0. The median Controlling Nutritional Status score was 2 (1-4). During the median 5.5-year follow-up period, 28 composite events occurred. Kaplan-Meier analysis demonstrated significant differences in the incidence of clinical endpoints between groups divided by each median Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Controlling Nutritional Status score (p = 0.007, 0.039, and 0.010, respectively). In multivariate Cox regression analysis, clinical endpoints were significantly associated with Geriatric Nutritional Risk Index (hazard ratio: 0.953, 95% confidence interval: 0.918-0.990), Prognostic Nutritional Index (hazard ratio: 0.942, 95% confidence interval: 0.892-0.996), and Controlling Nutritional Status score (hazard ratio: 1.230, 95% confidence interval: 1.056-1.433) after adjustment for factors associated in univariate Cox regression analysis. Malnutrition at diagnosis is a useful prognostic predictor for patients with pulmonary arterial hypertension.

DOI： 10.1002/pul2.12286

Myocardial Late Iodine Enhancement Using Photon-Counting Computed Tomography in Patients With Hypertrophic Cardiomyopathy Reviewed

Takahiro Nishihara, Toru Miyoshi, Noriaki Akagi, Mitsutaka Nakashima, Kazufumi Nakamura, Hiroshi Ito

Circulation Reports 5 ( 6 ) 269 - 270 2023.6

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

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

A Long-Term Survival Case of Coronary Artery Intimal Sarcoma Reviewed

Mitsutaka Nakashima, Kazufumi Nakamura, Masahiro Tabata, Zenichi Masuda, Takehiro Tanaka, Masatoki Yoshida, Yoshinobu Maeda, Shingo Kasahara, Hiroshi Ito

International Heart Journal 64 ( 3 ) 483 - 486 2023.5

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

Elderly Brothers With Fabry Disease Exhibiting Cardiac and Renal Manifestations Reviewed

Keiko Tanaka, Hitoshi Sugiyama, Hiroshi Morinaga, Akifumi Onishi, Yuzuki Kano, Hidemi Takeuchi, Kenji Tsuji, Motoki Kubo, Katsuyuki Tanabe, Haruhito A. Uchida, Kazufumi Nakamura, Jun Wada

Annals of Internal Medicine: Clinical Cases 2 ( 5 ) 2023.5

JCS 2023 Guideline on the Diagnosis and Treatment of Myocarditis Reviewed

Toshiyuki Nagai, Takayuki Inomata, Takashi Kohno, Takuma Sato, Atsushi Tada, Toru Kubo, Kazufumi Nakamura, Noriko Oyama-Manabe, Yoshihiko Ikeda, Takeo Fujino, Yasuhide Asaumi, Takahiro Okumura, Toshiyuki Yano, Kazuko Tajiri, Hiroyuki Matsuura, Yuichi Baba, Haruki Sunami, Shingo Tsujinaga, Yasutoshi Ota, Keiko Ohta-Ogo, Yusuke Ishikawa, Hideo Matama, Nobutaka Nagano, Kimi Sato, Kazushi Yasuda, Yasushi Sakata, Koichiro Kuwahara, Tohru Minamino, Minoru Ono, Toshihisa Anzai

Circulation Journal 87 ( 5 ) 674 - 754 2023.4

Molecular Research on Amyloidosis Reviewed

Kazufumi Nakamura

International Journal of Molecular Sciences 24 ( 8 ) 6980 - 6980 2023.4

Authorship：Lead author,　Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Amyloidosis is a large group of diseases that are caused by the deposition of insoluble amyloid fibrils formed by misfolded soluble proteins in organs or tissues [...]

DOI： 10.3390/ijms24086980

Shear Wave Dispersion Slope of the Liver Can Predict Adverse Outcomes in Patients with Pulmonary Hypertension Reviewed

Chikara Urabe, Yoichi Takaya, Rie Nakayama, Kazufumi Nakamura, Hiroshi Ito

International Heart Journal 64 ( 2 ) 230 - 236 2023.3

Prevalence of transthyretin amyloidosis among heart failure patients with preserved ejection fraction in Japan Reviewed

Takanori Naito, Kazufumi Nakamura, Yukio Abe, Hiroyuki Watanabe, Satoru Sakuragi, Yusuke Katayama, Hajime Kihara, Atsutaka Okizaki, Yusuke Kawai, Masaki Yoshikawa, Atsushi Takaishi, Hideki Fujio, Hiroaki Otsuka, Soichiro Ogura, Hiroshi Ito

ESC Heart Failure 10 ( 3 ) 1896 - 1906 2023.3

Authorship：Corresponding author Publishing type：Research paper (scientific journal) Publisher：Wiley

Abstract

Aims

Heart failure with preserved ejection fraction (HFpEF), which is caused by wide various conditions, has become a major public health problem. Transthyretin amyloid cardiomyopathy (ATTR‐CM), which is thought to be an underdiagnosed disease, can cause HFpEF. Non‐invasive diagnosis using ^99mTechnetium (Tc)‐pyrophosphate (PYP) scintigraphy enables accurate diagnosis of ATTR‐CM. The aim of this study was to clarify the prevalence and characteristics of ATTR‐CM among Japanese patients with HFpEF.

Methods and results

This study was a multicentre, prospective, observational study conducted in Japan. We enrolled 373 patients with HFpEF [left ventricular (LV) ejection fraction ≥50%] aged ≥65 years who were admitted to the department of cardiology from September 2018 to January 2022. A ^99mTc‐PYP scintigraphy scan was performed during admission in all eligible patients. Cardiac ^99mTc‐PYP retention was graded according to a previously reported visual scale ranging from 0 to 3 points. The scan was considered positive when it revealed moderate‐to‐severe ^99mTc‐PYP uptake (Grade 2–3) in both ventricles. Patients were divided into ATTR‐CM and non‐ATTR‐CM patients according to positive (Grade 2–3) or negative (Grade 0–1) 99mTc‐PYP scintigraphy, respectively. Medical history, blood tests, electrocardiogram, echocardiography, and magnetic resonance imaging in the two groups of patients were compared. Among the 373 patients with HFpEF, 53 patients (14.2%; 95% confidence interval: 10.7–17.7) showed positive uptake on ^99mTc‐PYP scintigraphy. An endomyocardial biopsy was performed in 32 patients and confirmed amyloidosis in all cases. There were no significant differences between the two groups in age, severity of heart failure as assessed by the New York Heart Association (NYHA) functional classification, renal function values, left ventricular ejection fraction, and tricuspid regurgitant pressure gradient (ATTR‐CM, n = 53 vs. non‐ATTR‐CM, n = 320). Patients in the ATTR‐CM group had a higher N‐terminal pro‐brain natriuretic peptide level [2314 (1081–3398) vs. 900 (415–1828), P < 0.001], higher sensitive troponin T level (0.074 ± 0.049 vs. 0.035 ± 0.038, P < 0.001), and higher mean LV maximal wall thickness [12.5 (11–14) vs. 10.5 (9.5–11.5), P < 0.001].

Conclusions

ATTR‐CM is an underdiagnosed disease with a significant prevalence in Japanese patients with HFpEF. This study showed that results of examinations for ATTR‐CM patients appear to be worse than those for non‐ATTR‐CM patients, but clinical severities of heart failure as assessed by the NYHA functional classification are similar in ATTR‐CM and non‐ATTR‐CM patients, and the clinical overlap between ATTR‐CM and non‐ATTR‐CM is high.

DOI： 10.1002/ehf2.14364

Heat Exposure Following the Rainy Season Is Associated With an Increased Risk of Cardiovascular Emergency Among the Elderly in Japan Reviewed

Ryohei Fujimoto, Etsuji Suzuki, Saori Kashima, Kazufumi Nakamura, Hiromichi Naito, Atsunori Nakao, Hiroshi Ito, Takashi Yorifuji

Journal of the American Heart Association 12 ( 6 ) 2023.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Ovid Technologies (Wolters Kluwer Health)

Background

Despite the impact of heat exposure caused by global warming, few studies have investigated the hourly effects of heat exposure and the risk of cardiovascular disease (CVD) in the elderly. We examined the associations between short‐term heat exposure and the risk of CVD in the elderly in Japan and evaluated possible effect‐measure modifications by rainy seasons that occur in East Asia.

 Methods and Results

We conducted a time‐stratified case–crossover study. The study included 6527 residents in Okayama City, Japan, aged ≥65 years who were transported to emergency hospitals between 2012 and 2019 for the onset of CVD during and a few months after the rainy seasons. We examined the linear associations between temperature and CVD‐related emergency calls for each year and for hourly preceding intervals before the emergency call during the most relevant months. Heat exposure during 1 month after the end of the rainy season was associated with CVD risk; the odds ratio (OR) for a 1° C increase in temperature was 1.34 (95% CI, 1.29–1.40). When we further explored the nonlinear association by using the natural cubic spline model, we found a J‐shaped relationship. Exposures 0 to 6 hours before the case event (preceding intervals 0–6 hours) were associated with CVD risk, particularly for the preceding interval 0 to 1 hour (OR, 1.33 [95% CI, 1.28–1.39]). For longer periods, the highest risk was at preceding intervals 0 to 23 hours (OR, 1.40 [95% CI, 1.34–1.46]).

 Conclusions

Elderly individuals may be more susceptible to CVD after heat exposure during the month after the rainy season. As shown by finer temporal resolution analyses, short‐term exposure to increasing temperature can trigger CVD onset.

DOI： 10.1161/jaha.122.027046

Association between Cardiovascular Disease and Liver Disease, from a Clinically Pragmatic Perspective as a Cardiologist. Reviewed International journal

Mitsutaka Nakashima, Kazufumi Nakamura, Takahiro Nishihara, Keishi Ichikawa, Rie Nakayama, Yoichi Takaya, Norihisa Toh, Satoshi Akagi, Toru Miyoshi, Teiji Akagi, Hiroshi Ito

Nutrients 15 ( 3 ) 2023.2

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Cardiovascular diseases and liver diseases are closely related. Non-alcoholic fatty liver disease has the same risk factors as those for atherosclerotic cardiovascular disease and may also be a risk factor for atherosclerotic cardiovascular disease on its own. Heart failure causes liver fibrosis, and liver fibrosis results in worsened cardiac preload and congestion. Although some previous reports regard the association between cardiovascular diseases and liver disease, the management strategy for liver disease in patients with cardiovascular diseases is not still established. This review summarized the association between cardiovascular diseases and liver disease. In patients with non-alcoholic fatty liver disease, the degree of liver fibrosis progresses with worsening cardiovascular prognosis. In patients with heart failure, liver fibrosis could be a prognostic marker. Liver stiffness assessed with shear wave elastography, the fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score is associated with both liver fibrosis in patients with liver diseases and worse prognosis in patients with heart failure. With the current population ageing, the importance of management for cardiovascular diseases and liver disease has been increasing. However, whether management and interventions for liver disease improve the prognosis of cardiovascular diseases has not been fully understood. Future investigations are needed.

DOI： 10.3390/nu15030748

Association between home-based exercise using a pedometer and clinical prognosis after endovascular treatment in patients with peripheral artery disease. Reviewed International journal

Kohei Kawamura, Kentaro Ejiri, Hironobu Toda, Toshiaki Yamanaka, Masato Taniguchi, Kenji Kawamoto, Koji Tokioka, Yoichiro Naito, Ryo Yoshioka, Eiji Karashima, Hideki Fujio, Soichiro Fuke, Yasukazu Fujiwara, Atsushi Takaishi, Kosuke Seiyama, Toru Miyoshi, Kazufumi Nakamura, Hiroshi Ito

Journal of cardiology 81 ( 2 ) 222 - 228 2023.2

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

BACKGROUND: Exercise therapy following endovascular treatment (EVT) is important for patients with peripheral artery disease (PAD); however, continuous exercise therapy is difficult to be performed in clinical practice. This study aimed to investigate the association between the implementation of home-based exercise using pedometers after EVT and 1-year clinical outcomes. METHODS: This multicenter observational prospective cohort registry included patients with PAD complaining of intermittent claudication who underwent EVT for aortoiliac and/or femoropopliteal artery lesions between January 2016 and March 2019. Patients were instructed to perform home-based exercises using a specific pedometer after EVT. The study population was divided into good and poor recording groups according to the frequency of the pedometer measurements. The good recording group was defined as those who completed ≥50 % of the prescribed daily pedometer recording during the follow-up period. The poor recording group was defined as those with an inability to use a pedometer and/or who completed <50 % of the prescribed daily pedometer recordings. The primary outcome was 1-year major adverse events (MAE), defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, target vessel revascularization, and major amputation of the target limb. RESULTS: The mean age was 74.4 years; 78 % were male. A total of 623 lesions were analyzed (58.7 % aortoiliac, 41.3 % femoropopliteal). At 1 year, a lower cumulative incidence of MAE was observed in the good recording group compared to that in the poor recording group [10/233 (4.3 %) vs. 35/267 (13.7 %) patients, respectively; p < 0.001]. Multivariate Cox regression analysis showed that patients in the good recording group had a lower hazard ratio for 1-year MAE (0.33; 95 % confidence interval, 0.16-0.68; p = 0.004) than that in the poor recording group. CONCLUSIONS: Good self-recording of pedometer measurements was associated with favorable prognosis in patients with PAD following EVT.

DOI： 10.1016/j.jjcc.2022.09.005

Microcalcification and 99mTc-Pyrophosphate Uptake without Increased Bone Metabolism in Cardiac Tissue from Patients with Transthyretin Cardiac Amyloidosis. Reviewed International journal

Atsushi Mori, Yukihiro Saito, Kazufumi Nakamura, Toshihiro Iida, Satoshi Akagi, Masashi Yoshida, Makiko Taniyama, Toru Miyoshi, Hiroshi Ito

International journal of molecular sciences 24 ( 3 ) 2023.1

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Transthyretin cardiac amyloidosis (ATTR-CA) is characterized by high 99mTc-labeled bone tracer uptake in the heart. However, the mechanism of bone tracer uptake into the heart remains controversial. Since bone tracer uptake into metastatic bone tumors is thought to be associated with increased bone metabolism, we examined 99mTc-pyrophosphate (PYP) scintigraphy findings, endomyocardial biopsy (EMB) tissue findings, and the expression of bone metabolism-related genes in the EMB tissues in patients with ATTR-CA, amyloid light-chain cardiac amyloidosis (AL-CA), and noncardiac amyloidosis (non-CA) in this study. The uptake of 99mTc-PYP in the heart was significantly higher in the ATTR-CA patients than in the AL-CA and non-CA patients. A higher percentage of ATTR-CA EMB tissue showed von Kossa-positive microparticles: ATTR-CA, 62%; AL-CA, 33%; and non-CA, 0%. Calcified microparticles were identified using transmission electron microscopy. However, none of the osteogenic marker genes, osteoclastic marker genes, or phosphate/pyrophosphate-related genes were upregulated in the EMB samples from ATTR-CA patients compared to those from AL-CA and non-CA patients. These results suggest that active calcification-promoting mechanisms are not involved in the microcalcification observed in the heart in ATTR-CA. The mechanisms explaining bone tracer uptake in the heart, which is stronger than that in the ribs, require further investigation.

DOI： 10.3390/ijms24031921

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

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease. Reviewed International journal

Ayako Chida-Nagai, Naoki Masaki, Kay Maeda, Konosuke Sasaki, Hiroki Sato, Jun Muneuchi, Yoshie Ochiai, Hiroomi Murayama, Masahiro Tahara, Atsuko Shiono, Atsushi Shinozuka, Fumihiko Kono, Daisuke Machida, Shinichi Toyooka, Seiichiro Sugimoto, Kazufumi Nakamura, Satoshi Akagi, Maiko Kondo, Shingo Kasahara, Yasuhiro Kotani, Junichi Koizumi, Katsuhiko Oda, Masako Harada, Daisuke Nakajima, Akira Murata, Hazumu Nagata, Koichi Yatsunami, Tomio Kobayashi, Yoshikiyo Matsunaga, Takahiro Inoue, Hiroyuki Yamagishi, Naomi Nakagawa, Katsuki Ohtani, Masaki Yamamoto, Yushi Ito, Tatsunori Hokosaki, Yuta Kuwahara, Satoshi Masutani, Koji Nomura, Tsutomu Wada, Hirofumi Sawada, Masayuki Abiko, Tatsunori Takahashi, Yuichi Ishikawa, Seigo Okada, Atsushi Naitoh, Takako Toda, Tatsuya Ando, Akihiro Masuzawa, Shinsuke Hoshino, Masaaki Kawada, Yuichi Nomura, Kentaro Ueno, Naoki Ohashi, Tsuyoshi Tachibana, Yuchen Cao, Hideaki Ueda, Sadamitsu Yanagi, Masaaki Koide, Norie Mitsushita, Kouji Higashi, Yoshihiro Minosaki, Tomohiro Hayashi, Takashi Okamoto, Kenji Kuraishi, Eiji Ehara, Hidekazu Ishida, Hitoshi Horigome, Takashi Murakami, Kohta Takei, Taku Ishii, Gen Harada, Yasutaka Hirata, Jun Maeda, Shunsuke Tatebe, Chiharu Ota, Yasunobu Hayabuchi, Hisanori Sakazaki, Takashi Sasaki, Keiichi Hirono, Sayo Suzuki, Masahiro Yasuda, Atsuhito Takeda, Madoka Sawai, Kagami Miyaji, Atsushi Kitagawa, Yosuke Nakai, Nobuyuki Kakimoto, Kouta Agematsu, Atsushi Manabe, Yoshikatsu Saiki

Frontiers in cardiovascular medicine 10 1212882 - 1212882 2023

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

AIMS: Limited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH. METHODS: This retrospective study examined lung pathology images of 764 patients with CHD-PAH aged <20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death. RESULTS: The 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD <2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45-13.73; P = .009). CONCLUSIONS: The IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered.

DOI： 10.3389/fcvm.2023.1212882

A hyperechoic mass in femoral vein

Naoko Kaku, Hiroki Sugiyama, Kazufumi Nakamura, Tomoki Furutani, Takashi Hongo, Hiroshi Ito

Clinical Case Reports 10 ( 11 ) 2022.11

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

Abstract

Here, we present a case of fat embolism syndrome (FES) in which ultrasound sonography and computed tomography successfully visualized fat embolus in the femoral vein. A multimodality approach was particularly useful for early and specific diagnosis.

DOI： 10.1002/ccr3.6552

Repeated Syncope During Exercise as a Result of Anomalous Origin of Left Coronary Artery With Intramural Aortic Course in a Teenage Boy Reviewed

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.6552

Naofumi Amioka, Kazufumi Nakamura, Naoaki Matsuo, Atsuyuki Watanabe, Yasuhiro Kotani, Shingo Kasahara, Hiroshi Ito

Texas Heart Institute Journal 49 ( 6 ) 2022.11

Authorship：Corresponding author Publishing type：Research paper (scientific journal) Publisher：Texas Heart Institute Journal

Anomalous origin of the left coronary artery from the opposite sinus of Valsalva with an intramural aortic course (L-ACAOS-IM) can cause syncope, sometimes as a prodrome of lethal events, including sudden cardiac death, in young athletes. The detailed mechanism of syncope in patients with L-ACAOS-IM is still unclear. This case report describes a 17-year-old boy who presented to the hospital because of syncope following chest pain with increasing frequency during exercise, such as playing soccer and running. In a treadmill exercise test, a decrease in blood pressure was seen (from 99/56 mm Hg to 68/38 mm Hg); chest pain and faintness accompanied by ST-segment elevation in lead aVR and ST-segment depression at other leads on electrocardiography were noted. These findings and symptoms disappeared spontaneously within a few minutes while clinicians prepared for emergency medications. Coronary computed tomography angiography (CCTA) showed that the origin of the left coronary artery (LCA) was the opposite sinus of Valsalva, and the course of the LCA was through the aortic wall toward the left coronary sinus. He was diagnosed with L-ACAOS-IM. After surgical treatment by unroofing the intramural part of the LCA and reconstructing a neo-ostium, he no longer experienced syncope during exercise. This case suggests that low cardiac output caused by myocardial ischemia, not life-threatening arrythmia, is a main mechanism of syncope in patients with L-ACAOS-IM. Consideration should be given to performing CCTA before an exercise stress test for young patients with syncope and chest pain to avoid the risk of severe myocardial ischemia.

DOI： 10.14503/thij-21-7677

Cardio-Ankle Vascular Index as an Arterial Stiffness Marker Improves the Prediction of Cardiovascular Events in Patients without Cardiovascular Diseases Reviewed

Yuko Okamoto, Toru Miyoshi, Keishi Ichikawa, Yoichi Takaya, Kazufumi Nakamura, Hiroshi Ito

Journal of Cardiovascular Development and Disease 9 ( 11 ) 368 - 368 2022.10

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Several studies have reported that the cardio-ankle vascular index (CAVI), a non-invasive measurement of arterial stiffness, is associated with the incidence of cardiovascular events. We investigated whether adding CAVI to a risk score improves the prediction of cardiovascular events in the setting of primary prevention. This retrospective observational study included consecutive 554 outpatients with cardiovascular disease risk factors but without known cardiovascular disease (68 ± 9 years, 64% men). The CAVI was measured using the VaSera vascular screening system. Major adverse cardiovascular events (MACE) included cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization. During a median follow-up of 4.3 years, cardiovascular events occurred in 65 patients (11.7%). Multivariate Cox analysis showed that abnormal CAVI (>9.0) was significantly associated with the incidence of MACE (hazard ratio 2.31, 95% confidence interval 1.27–4.18). The addition of CAVI to the Suita score, a conventional risk score for coronary heart disease in Japan, significantly improved the C statics from 0.642 to 0.713 (p = 0.04). In addition to a conventional risk score, CAVI improved the prediction of cardiovascular events in patients with cardiovascular disease risk factors but without known cardiovascular diseases.

DOI： 10.3390/jcdd9110368

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 Reviewed

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

Effects of luseogliflozin and voglibose on high-risk lipid profiles and inflammatory markers in diabetes patients with heart failure. Reviewed International journal

Kentaro Ejiri, Toru Miyoshi, Hajime Kihara, Yoshiki Hata, Toshihiko Nagano, Atsushi Takaishi, Hironobu Toda, Seiji Namba, Yoichi Nakamura, Satoshi Akagi, Satoru Sakuragi, Taro Minagawa, Yusuke Kawai, Nobuhiro Nishii, Soichiro Fuke, Masaki Yoshikawa, Kazufumi Nakamura, Hiroshi Ito

Scientific reports 12 ( 1 ) 15449 - 15449 2022.9

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

Sodium-glucose cotransporter 2 inhibitors could reduce cardiovascular events in patients with heart failure irrespective of diabetes status. In this prespecified sub-analysis of randomised-controlled trial, we investigated the efficacy of luseogliflozin (2.5 mg daily), a sodium-glucose cotransporter 2 inhibitor, with that of voglibose (0.6 mg daily), an alpha-glucosidase inhibitor, on high-risk lipid profile and inflammatory markers in patients with type-2 diabetes and heart failure. Among the 157 patients studied, there were no significant differences in the mean malondialdehyde LDL or small-dense LDL cholesterol levels between the luseogliflozin and voglibose groups (percent change: 0.2% vs. - 0.6%, p = 0.93; - 1.7% vs. - 8.6%, p = 0.21) after 12 weeks in comparison to levels at the baseline. No significant difference was observed between the two groups in the adiponectin and high-sensitivity C-reactive protein levels after 12 weeks compared to the baseline levels (percent change, - 1.6% vs. - 4.0% and 22.5% vs. 10.0%; p = 0.52 and p = 0.55, respectively). In conclusion, in patients with type-2 diabetes and heart failure, compared to voglibose, luseogliflozin did not significantly improve the high-risk lipoprotein profile including malondialdehyde LDL and small-dense LDL cholesterol or the levels of inflammatory markers, including adiponectin and high-sensitivity C-reactive protein.Trial registration: Trial number: UMIN-CTR, UMIN000018395; Registered 23 July 2015; URL: https://www.umin.ac.jp/ctr/index.htm .

DOI： 10.1038/s41598-022-19371-6

High platelet reactivity is a predictor of left ventricular remodelling in patients with acute myocardial infarction Reviewed

Masahiro Tsuji, Yusuke Kawai, Toru Miyoshi, Eisuke Saito, Kohei Kawamura, Tamaki Ono, Koji Tokioka, Tohru Ohe, Kazufumi Nakamura, Hiroshi Ito

ESC Heart Failure 9 ( 5 ) 3565 - 3574 2022.7

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

Abstract

Aims

Acute myocardial infarction (AMI) is associated with left ventricular remodelling (LVR), which leads to progressive heart failure. Platelets play a pivotal role in promoting systemic and cardiac inflammatory responses during the complex process of myocardial wound healing or repair following AMI. This study aimed to investigate the impact of platelet reactivity immediately after primary percutaneous coronary intervention (PCI) on LVR in AMI patients with ST‐segment (STEMI) and non‐ST‐segment elevation (NSTEMI).

Methods and results

This prospective, single‐centre, observational study included 182 patients with AMI who underwent primary PCI (107 patient with STEMI and 75 patients with NSTEMI). Patients were administered a loading dose of aspirin plus prasugrel before the procedure, and platelet reactivity was assessed using the VerifyNow P2Y12 assay immediately after PCI. Echocardiography was performed before discharge and during the chronic phase (8 ± 3 months after discharge). LVR was defined as a relative ≥20% increase in left ventricular end‐diastolic volume index (LVEDVI). LVR in chronic phase was found in 34 patients (18.7%) whose platelet reactivity was significantly higher than those without LVR (259.6 ± 61.5 and 213.1 ± 74.8 P2Y12 reaction units [PRU]; P = 0.001). The occurrence of LVR did not differ between patients with STEMI and patients with NSTEMI (21.5% and 14.7%; P = 0.33). The optimal cut‐off value of platelet reactivity for discriminating LVR was ≥245 PRU. LVEDVI significantly decreased at chronic phase in patients without high platelet reactivity (<245 PRU) (from 49.2 ± 13.5 to 45.4 ± 15.8 mL/m²; P = 0.02), but not in patients with high platelet reactivity (≥d245 PRU) (P = 0.06). Multivariate logistic analysis showed that high platelet reactivity was an independent predictor of LVR after adjusting for LVEDVI before discharge (odds ratio, 4.13; 95% confidence interval, 1.85–9.79).

Conclusions

High platelet reactivity measured immediately after PCI was a predictor of LVR in patients with AMI during the chronic phase. The role of antiplatelet therapy on inflammation in the myocardium is a promising area for further research.

DOI： 10.1002/ehf2.14100

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ehf2.14100

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

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

Authorship：Lead author 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

Differences in extracellular fluid volume between acute heart failure patients with and without high systolic blood pressure Reviewed

Yusuke Namba, Kei Yunoki, Kazufumi Nakamura, Kentaro Ejiri, Takefumi Oka, Hiroshi Ito

ESC Heart Failure 9 ( 5 ) 3358 - 3366 2022.7

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

Abstract

Aims

Some reports have suggested that hypertensive acute heart failure (AHF) is caused by intravascular congestion, not interstitial congestion. We evaluated the differences in extracellular fluid volume assessed by bioelectrical impedance analysis (BIA) between AHF patients with and without high systolic blood pressure (sBP).

Methods

This prospective single‐centre study (UMIN000030266) included 178 patients hospitalized due to AHF between September 2017 and August 2018. We calculated extracellular water (ECW), intracellular water (ICW), total body water (TBW), and ECW‐to‐TBW ratio (oedema index: EI) by BIA and evaluated conventional parameters as follows: weight, N‐terminal pro brain natriuretic peptide values, and echocardiography parameters on admission and before discharge. One‐year outcomes included all‐cause death and re‐admission due to heart failure. We compared patients with sBP > 140 mmHg on admission [clinical scenario 1 (CS1) group] and with sBP of ≤140 mmHg on admission (non‐CS1 group).

Results

The mean age of the patients was 79.5 ± 11.1 years, and 48.9% of the patients were female. EI on admission of 83 patients in the CS1 group was lower than that of 95 patients in the non‐CS1 group. The change in EI from admission to before discharge was no significant in the CS1 group but was significant in the non‐CS1 group. Comparing the changes from admission to before discharge between the CS1 and the non‐CS1 group, delta ECW, delta ICW, delta TBW, and delta EI of the CS1 group were significantly smaller than those of the non‐CS1 group. During the 1‐year follow‐up period after discharge of the 178 patients, the numbers of deaths and re‐admissions due to acute HF were 26 (15%) and 49 (28%), respectively. Patients with high EI before discharge [>0.408 (median)] had significantly more cardiac events than patients with low EI [hazard ratio (HR): 2.15, 95% confidence interval (CI): 1.30–3.55]. Cox regression analysis revealed that higher EI as a continuous variable was significantly associated with worse outcome in non‐CS1 group (HR: 1.46, 95% CI: 1.13–1.87), but not significantly associated with worse outcome in CS1 group (HR: 1.29, 95% CI: 0.98–1.69).

Conclusions

EI on admission in patients with high sBP was not elevated, and changes in ECW, ICW, TBW, and EI in patients with high sBP were smaller than those in patients without high sBP. EI measured by BIA could distinguish AHF with interstitial or intravascular congestion.

DOI： 10.1002/ehf2.14067

Myocardial T-Lymphocytes as a Prognostic Risk-Stratifying Marker of Dilated Cardiomyopathy ― Results of the Multicenter Registry to Investigate Inflammatory Cell Infiltration in Dilated Cardiomyopathy in Tissues of Endomyocardial Biopsy (INDICATE Study) ― Reviewed

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ehf2.14067

Keiko Ohta-Ogo, Yasuo Sugano, Soshiro Ogata, Takafumi Nakayama, Takahiro Komori, Kazuo Eguchi, Kaoru Dohi, Tetsuro Yokokawa, Hiromitsu Kanamori, Shigeyuki Nishimura, Kazufumi Nakamura, Yoshihiko Ikeda, Kunihiro Nishimura, Genzou Takemura, Toshihisa Anzai, Michiaki Hiroe, Kinta Hatakeyama, Hatsue Ishibashi-Ueda, Kyoko Imanaka-Yoshida

Circulation Journal 86 ( 7 ) 1092 - 1101 2022.6

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

Efficacy of shear wave elasticity for predicting clinical outcomes in patients with significant tricuspid regurgitation Reviewed

Rie Nakayama, Yoichi Takaya, Kazufumi Nakamura, Rika Takemoto, Norihisa Toh, Hiroshi Ito

Heart and Vessels 37 ( 11 ) 1866 - 1872 2022.5

Quantification of Lung Perfusion Blood Volume in Dual-Energy Computed Tomography in Patients with Pulmonary Hypertension. Reviewed International journal

Satoko Ugawa, Satoshi Akagi, Kentaro Ejiri, Kazufumi Nakamura, Hiroshi Ito

Life (Basel, Switzerland) 12 ( 5 ) 2022.5

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

Dual-energy computed tomography (DECT) is a promising technique for the assessment of the lung perfused blood volume (LPBV) in the lung parenchyma. This study was performed to compare the LPBV by DECT of patients with pulmonary hypertension (PH) and controls and to evaluate the association between the LPBV and the perfusion ratio derived by lung perfusion scintigraphy. This study involved 45 patients who underwent DECT (25 patients with PH and 20 controls). We measured the total LPBV and distribution of the LPBV in each lung. The total LPBV was significantly lower in the PH group than the control group (38 ± 9 vs. 45 ± 8 HU, p = 0.024). Significant differences were observed between the LPBV of the upper lung of the PH and control groups (34 ± 10 vs. 47 ± 10, p = 0.021 and 37 ± 10 vs. 47 ± 8, p < 0.001). A significant correlation was observed between the LPBV and the lung perfusion scintigraphy. A lower total LPBV and lower LPBV of the upper lung as detected by DECT might be specific findings of PH.

DOI： 10.3390/life12050684

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

Authorship：Corresponding author 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

Pathophysiology and Treatment of Diabetic Cardiomyopathy and Heart Failure in Patients with Diabetes Mellitus Reviewed

Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Satoshi Akagi, Yukihiro Saito, Kentaro Ejiri, Naoaki Matsuo, Keishi Ichikawa, Keiichiro Iwasaki, Takanori Naito, Yusuke Namba, Masatoki Yoshida, Hiroki Sugiyama, Hiroshi Ito

International Journal of Molecular Sciences 23 ( 7 ) 3587 - 3587 2022.3

Authorship：Lead author,　Corresponding author Publishing type：Research paper (scientific journal) Publisher：MDPI AG

There is a close relationship between diabetes mellitus and heart failure, and diabetes is an independent risk factor for heart failure. Diabetes and heart failure are linked by not only the complication of ischemic heart disease, but also by metabolic disorders such as glucose toxicity and lipotoxicity based on insulin resistance. Cardiac dysfunction in the absence of coronary artery disease, hypertension, and valvular disease is called diabetic cardiomyopathy. Diabetes-induced hyperglycemia and hyperinsulinemia lead to capillary damage, myocardial fibrosis, and myocardial hypertrophy with mitochondrial dysfunction. Lipotoxicity with extensive fat deposits or lipid droplets is observed on cardiomyocytes. Furthermore, increased oxidative stress and inflammation cause cardiac fibrosis and hypertrophy. Treatment with a sodium glucose cotransporter 2 (SGLT2) inhibitor is currently one of the most effective treatments for heart failure associated with diabetes. However, an effective treatment for lipotoxicity of the myocardium has not yet been established, and the establishment of an effective treatment is needed in the future. This review provides an overview of heart failure in diabetic patients for the clinical practice of clinicians.

DOI： 10.3390/ijms23073587

LCZ696 ameliorates doxorubicin-induced cardiomyocyte toxicity in rats. Reviewed International journal

Toru Miyoshi, Kazufumi Nakamura, Naofumi Amioka, Omer F Hatipoglu, Tomoko Yonezawa, Yukihiro Saito, Masashi Yoshida, Satoshi Akagi, Hiroshi Ito

Scientific reports 12 ( 1 ) 4930 - 4930 2022.3

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

Doxorubicin (DOX)-based chemotherapy induces cardiotoxicity, which is considered the main bottleneck for its clinical application. In this study, we investigated the potential benefit of LCZ696, an angiotensin receptor-neprilysin inhibitor against DOX-induced cardiotoxicity in rats and H9c2 cells and determined whether the mechanism underlying any such effects involves its antioxidant activity. Male Sprague-Dawley rats were randomly separated into four groups, each consisting of 15 rats (DOX (1.5 mg/kg/day intraperitoneally for 10 days followed by non-treatment for 8 days); DOX + valsartan (31 mg/kg/day by gavage from day 1 to day 18); DOX + LCZ696 (68 mg/kg/day by gavage from day 1 to day 18); and control (saline intraperitoneally for 10 days). DOX-induced elevation of cardiac troponin T levels on day 18 was significantly reduced by LCZ696, but not valsartan. The DOX-induced increase in myocardial reactive oxygen species (ROS) levels determined using dihydroethidium was significantly ameliorated by LCZ696, but not valsartan, and was accompanied by the suppression of DOX-induced increase in p47phox. LCZ696 recovered the DOX-induced decrease in phosphorylation of adenosine monophosphate-activated protein kinase and increased the ratio of Bax and Bcl-2. In H9c2 cardiomyocytes, LCZ696 reduced DOX-induced mitochondrial ROS generation and improved cell viability more than valsartan. Our findings indicated that LCZ696 ameliorated DOX-induced cardiotoxicity in rat hearts in vivo and in vitro, possibly by mediating a decrease in oxidative stress.

DOI： 10.1038/s41598-022-09094-z

The number of circulating CD34-positive cells is an independent predictor of coronary artery calcification progression: Sub-analysis of a prospective multicenter study. Reviewed International journal

Keishi Ichikawa, Toru Miyoshi, Kazuhiro Osawa, Takashi Miki, Kunihisa Kohno, Kazufumi Nakamura, Yasushi Koyama, Hiroshi Ito

Cardiology journal 2022.3

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

BACKGROUND: Decreases in circulating CD34-positive cells are associated with increases in cardiovascular events. We investigated the association between the number of CD34-positive cells and the progression of coronary artery calcification (CAC), a marker of atherosclerosis, in patients with hypercholesteremia under statin therapy in a sub-analysis of a multicenter study. METHODS: In the principal study, patients with CAC scores of 1-999 were treated with pitavastatin. Measurement of CAC by non-enhanced computed tomography and a blood test were performed at baseline and at 1-year follow-up. Patients were divided into two groups: CAC progression (change in CAC score > 0) and non-progression. The number of circulating CD34-positive cells was counted using flow cytometry. RESULTS: A total of 156 patients (mean age 67 years, 55% men) were included in this sub-analysis. CD34 positive cell numbers at baseline as a continuous variable was inversely correlated with annual change in the log-transformed CAC score (r = -0.19, p = 0.02). When patients were divided into high and low CD34 groups based on the median value of 0.8 cells/μL, the adjusted change in CAC score in the low-CD34 group was significantly greater than that in the high-CD34 group (54.2% vs. 20.8%, respectively, p = 0.04). In multiple logistic analysis, a low CD34-positive cell number was an independent predictor of CAC progression, with an odds ratio of 2.88 (95% confidence interval 1.28-6.49, p = 0.01). CONCLUSIONS: Low numbers of CD34-positive cells are associated with CAC progression in patients with hypercholesterolemia under statin therapy. The number of CD34-positive cells may help to identify patients at increased cardiovascular risk.

DOI： 10.5603/CJ.a2021.0151

Fragmented QRS as a predictor of cardiac events in patients with cardiac sarcoidosis. Reviewed 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 2022.3

Authorship：Corresponding author 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

Effects of luseogliflozin on estimated plasma volume in patients with heart failure with preserved ejection fraction. Reviewed International journal

Mitsutaka Nakashima, Toru Miyoshi, Kentaro Ejiri, Hajime Kihara, Yoshiki Hata, Toshihiko Nagano, Atsushi Takaishi, Hironobu Toda, Seiji Nanba, Yoichi Nakamura, Satoshi Akagi, Satoru Sakuragi, Taro Minagawa, Yusuke Kawai, Nobuhiro Nishii, Soichiro Fuke, Masaki Yoshikawa, Kazufumi Nakamura, Hiroshi Ito

ESC heart failure 9 ( 1 ) 712 - 720 2022.2

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

AIMS: Sodium glucose co-transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: This study was a post-hoc analysis of the MUSCAT-HF trial (UMIN000018395), a multicentre, prospective, open-label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed-effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group-difference -6.43% [95% confidence interval (CI): -9.11 to -3.74]}, at Week 12 [-8.73% (95%CI: -11.40 to -6.05)], and at Week 24 [-11.02% (95%CI: -13.71 to -8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log-transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019). CONCLUSIONS: Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF.

DOI： 10.1002/ehf2.13683

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

Incremental prognostic value of non-alcoholic fatty liver disease over coronary computed tomography angiography findings in patients with suspected coronary artery disease. Reviewed 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 2022.1

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

Assessment of congestion and clinical outcomes in patients with chronic heart failure using shear wave elasticity Reviewed

Rie Nakayama, Yoichi Takaya, Kazufumi Nakamura, Rika Takemoto, Norihisa Toh, Hiroshi Ito

ESC Heart Failure 9 ( 2 ) 1279 - 1286 2022.1

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

Abstract

Aims

The relief of congestion is essential for the prevention of worsening heart failure (HF) resulting in hospitalizations. Assessment of the degree of organ congestion in the chronic phase of HF is important for determining therapeutic strategies. The aim of this study was to evaluate the efficacy of shear wave (SW) elasticity for assessing congestion and clinical outcomes in patients with chronic HF.

Methods and results

We prospectively enrolled 345 consecutive patients with chronic HF who underwent SW elastography at outpatient clinic. Patients were divided into two groups according to the median value of SW elasticity: low group (SW elasticity <6.4 kPa, n = 176) and high group (SW elasticity ≥6.4 kPa, n = 169). The endpoint was cardiovascular death or hospitalization for HF. During the median follow‐up period of 19 months (range: 7–36 months), cardiovascular death or hospitalization for HF occurred in 4 patients of low group and 27 patients of high group. In high group, 8 patients died, and 19 patients were hospitalized for HF. In low group, 3 patients died, and 1 patient was hospitalized. Kaplan–Meier analysis showed that the event‐free survival rate was worse in high group than in low group (log‐rank test, P = 0.004). After adjusting for variables, high SW elasticity was independently related to cardiac events. In multivariate regression analysis, SW elasticity was correlated with left atrial volume index, early diastolic mitral inflow velocity to mitral annular velocity ratio, and inferior vena cava diameter.

Conclusions

The SW elasticity reflected haemodynamic congestion in patients with chronic HF, which was related to cardiac events.

DOI： 10.1002/ehf2.13809

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ehf2.13809

Rapidly Progressive Stenosis of the Left Main Trunk Ostium Starting 21 Months After Stent Implantation Reviewed

Y. Naito, M. Yoshikawa, K. Nakamura, M. Kubo, H. Sugiyama, H. Suzuki

Acta Med Okayama 76 ( 1 ) 99 - 104 2022.1

Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms. Reviewed International journal

Naofumi Amioka, Toru Miyoshi, Tomoko Yonezawa, Megumi Kondo, Satoshi Akagi, Masashi Yoshida, Yukihiro Saito, Kazufumi Nakamura, Hiroshi Ito

Frontiers in cardiovascular medicine 9 904215 - 904215 2022

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

Background: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) agonist, on AAA formation and rupture. Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE - / - mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS). Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-α in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPARα significantly attenuated the anti-oxidative effect of pemafibrate. Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.

DOI： 10.3389/fcvm.2022.904215

Molecular Mechanisms of Cardiac Amyloidosis. Reviewed International journal

Yukihiro Saito, Kazufumi Nakamura, Hiroshi Ito

International journal of molecular sciences 23 ( 1 ) 2021.12

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Cardiac involvement has a profound effect on the prognosis of patients with systemic amyloidosis. Therapeutic methods for suppressing the production of causative proteins have been developed for ATTR amyloidosis and AL amyloidosis, which show cardiac involvement, and the prognosis has been improved. However, a method for removing deposited amyloid has not been established. Methods for reducing cytotoxicity caused by amyloid deposition and amyloid precursor protein to protect cardiovascular cells are also needed. In this review, we outline the molecular mechanisms and treatments of cardiac amyloidosis.

DOI： 10.3390/ijms23010025

心内膜心筋生検による心臓サルコイドーシスの診断(Diagnosis of Cardiac Sarcoidosis by Endomyocardial Biopsy)

中村一文, 網岡尚史, 中川晃志, 赤木達, 伊藤浩

日本循環器学会学術集会抄録集 85回 SS05 - 3 2021.3

Effects of Dual Initial Combination Therapy With Macitentan Plus Riociguat or Macitentan Plus Selexipag on Hemodynamics in Patients With Pulmonary Arterial Hypertension (SETOUCHI-PH Study) - Protocol of a Multicenter Randomized Control Trial.

Satoshi Akagi, Yoshihiro Dohi, Kaori Ishikawa, Kayoko Kubota, Koshin Horimoto, Shusuke Yagi, Tetsuo Hirata, Eiichiro Yamamoto, Hiroshi Ito, Kazufumi Nakamura

Circulation reports 3 ( 2 ) 105 - 109 2021.1

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

Background: The latest guideline from the European Society of Cardiology and European Respiratory Society recommends initial combination therapy with oral pulmonary arterial hypertension (PAH)-specific drugs in PAH patients with World Health Organization functional class (WHO-FC) II or III. However, whether this initial combination therapy improves hemodynamics and clinical failure events regardless of the combination of PAH-specific drugs remains unknown. This study was designed to evaluate whether the initial combination therapy with macitentan plus riociguat or macitentan plus selexipag showed equal efficacy in reducing pulmonary vascular resistance (PVR) 8 months after administration. Methods and Results: This study is a multicenter randomized control trial. PAH subjects with WHO-FC II or III will be randomized (1 : 1) into initial combination therapy with either macitentan plus riociguat or macitentan plus selexipag, and will be observed 8 months after the initiation of treatment. The primary endpoint will be the difference in the change ratio of PVR from baseline to after 8 months of treatment. Conclusions: The SETOUCHI-PH study will clarify whether initial combination therapy with macitentan plus riociguat or macitentan plus selexipag results in equal reductions in PVR 8 months after administration.

DOI： 10.1253/circrep.CR-20-0133

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

Correction to: Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet. International journal

Masatoki Yoshida, Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Megumi Kondo, Kaoru Akazawa, Tomonari Kimura, Hiroaki Ohtsuka, Yuko Ohno, Daiji Miura, Hiroshi Ito

Cardiovascular diabetology 19 ( 1 ) 213 - 213 2020.12

心アミロイドーシスの療総論 (心不全, 不整脈, 血栓塞栓症に対する治療)

宮本真和, 中村一文

24 ( 11 ) 1078 - 1083 2020.11

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

Chemoradiation therapy for non-small cell lung cancer exacerbates thoracic aortic calcification determined by computed tomography Reviewed

Heart Vessels 35 ( 10 ) 1401 - 1408 2020.10

Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet Reviewed

Yoshida M, Nakamura K, Miyoshi T, Yoshida M, Kondo M, Akazawa K, Kimura T, Ohtsuka H, Ohno Y, Miura D, Ito H

Cardiovasc Diabetol 19 ( 1 ) 149 2020.9

Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet. International journal

Masatoki Yoshida, Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Megumi Kondo, Kaoru Akazawa, Tomonari Kimura, Hiroaki Ohtsuka, Yuko Ohno, Daiji Miura, Hiroshi Ito

Cardiovascular diabetology 19 ( 1 ) 149 - 149 2020.9

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

BACKGROUND: Statins suppress the progression of atherosclerosis by reducing low-density lipoprotein (LDL) cholesterol levels. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor α modulator, is expected to reduce residual risk factors including high triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol during statin treatment. However, it is not known if statin therapy with add-on pemafibrate improves the progression of atherosclerosis. The aim of this study was to assess the effect of combination therapy with pitavastatin and pemafibrate on lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. METHODS: Seven-week-old male Dahl salt-sensitive (DS) rats were divided into the following five treatment groups (normal diet (ND) plus vehicle, high-salt and high-fat diet (HD) plus vehicle, HD plus pitavastatin (0.3 mg/kg/day), HD plus pemafibrate (K-877) (0.5 mg/kg/day), and HD plus combination of pitavastatin and pemafibrate) and treated for 12 weeks. At 19 weeks, endothelium-dependent relaxation of the thoracic aorta in response to acetylcholine was evaluated. RESULTS: After feeding for 12 weeks, systolic blood pressure and plasma levels of total cholesterol were significantly higher in the HD-vehicle group compared with the ND-vehicle group. Combination therapy with pitavastatin and pemafibrate significantly reduced systolic blood pressure, TG levels, including total, chylomicron (CM), very LDL (VLDL), HDL-TG, and cholesterol levels, including total, CM, VLDL, and LDL-cholesterol, compared with vehicle treatment. Acetylcholine caused concentration-dependent relaxation of thoracic aorta rings that were pre-contracted with phenylephrine in all rats. Relaxation rates in the HD-vehicle group were significantly lower compared with the ND-vehicle group. Relaxation rates in the HD-combination of pitavastatin and pemafibrate group significantly increased compared with the HD-vehicle group, although neither medication alone ameliorated relaxation rates significantly. Western blotting experiments showed increased phosphorylated endothelial nitric oxide synthase protein expression in aortas from rats in the HD-pemafibrate group and the HD-combination group compared with the HD-vehicle group. However, the expression levels did not respond significantly to pitavastatin alone. CONCLUSIONS: Combination therapy with pitavastatin and pemafibrate improved lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Pemafibrate as an add-on strategy to statins may be useful for preventing atherosclerosis progression.

DOI： 10.1186/s12933-020-01132-2

Effect of Luseogliflozin on Heart Failure With Preserved Ejection Fraction in Patients With Diabetes Mellitus Reviewed

Ejiri K, Miyoshi T, Kihara H, Hata Y, Nagano T, Takaishi A, Toda H, Nanba S, Nakamura Y, Akagi S, Sakuragi S, Minagawa T, Kawai Y, Nishii N, Fuke S, Yoshikawa M, Nakamura K, Ito H; MUSCAT‐HF Study Investigators

J Am Heart Assoc 9 ( 16 ) e015103 2020.8

松田論文に対するEditoial Comment –SIADHの診断と治療

中村一文

心臓 52 ( 8 ) 897 2020.8

Effects of Eicosapentaenoic Acid on Arterial Calcification Reviewed

Saito Y, Nakamura K, Ito H

Int J Mol Sci 21 ( 15 ) 5455 2020.7

Prognostic Value of Coronary Computed Tomographic Angiography in Patients With Nonalcoholic Fatty Liver Disease Reviewed

Ichikawa K, Miyoshi T, Osawa K, Miki T, Nakamura K, Ito H

JACC Cardiovasc Imaging 13 ( 7 ) 1628 - 1630 2020.7

循環器内科医が生理査に期待するもの－無くてはならない心電図・超音波－

中村一文

生物試料分析 43 ( 3 ) 171 - 175 2020.6

【臨床医が知っていてほしい循環器基礎研究最新の成果】心不全　酸化ストレスは心不全の原因か?

中村一文、網岡尚史、三好　亨、伊藤　浩

循環器内科 87 ( 5 ) 597 - 600 2020.5

Deficiency of CD44 prevents thoracic aortic dissection in a murine model Reviewed

Hatipoglu OF, Miyoshi T, Yonezawa T, Kondo M, Amioka N, Yoshida M, Akagi S, Nakamura K, Hirohata S, Ito H

Sci Rep 10 ( 1 ) 6869 2020.4

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

Toda H, Nakamura K, Shimizu K, Ejiri K, Iwano T, Miyoshi T, Nakagawa K, Yoshida M, Watanabe A, Nishii N, Hikasa Y, Hayashi M, Morita H, Morimatsu H, Ito H; MAMACARI Investigators.

Circ J 84 ( 4 ) 642 - 649 2020.3

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

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

Successful Transition from Phosphodiesterase-5 Inhibitors to Riociguat Without a Washout Period in Patients With Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: A Pilot Cohort Study Reviewed

Kuroda K, Akagi S, Nakamura K, Sarashina T, Ejiri K, Ito H

Heart Lung Circ 29 ( 3 ) 331 - 336 2020.3

【第6回世界肺高血圧学会2018のステートメントを読み解く　アンメット・メディカル・ニーズは解決されたのか?】右心室および肺循環の病態生理学

中村一文, 赤木達, 江尻健太郎, 伊藤　浩

呼吸器内科 37 ( 3 ) 233 - 237 2020.3

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

Ogura S, Nakamura K, Morita H, Toh N, Nakagawa K, Yoshida M, Watanabe A, Nishii N, Miyoshi T, Ito H

Circ J 84 ( 3 ) 487 - 494 2020.2

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 Reviewed

84 ( 3 ) 456 - 462 2020.2

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

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

Chemotherapy Improved Pulmonary Arterial Hypertension in a Patient with Chronic-Active Epstein-Barr Virus Infection Reviewed

Akagi S, Miki T, Sando Y, Fujii N, Sarashina T, Nakamura K, Ito H

Int Heart J 61 ( 1 ) 191 - 194 2020.1

Marked Reduction of Pulmonary Artery Pressure After Registration for Lung Transplantation Is Associated With Long-Term Survival in Patients With Pulmonary Arterial Hypertension　- Cohort Study Reviewed

Akagi S, Matsubara H, Nakamura K, Oto T, Ejiri K, Ito H

Circ J 84 ( 2 ) 245 - 251 2020.1

Fontan術後の複数の心房頻拍に対しRythmiaによるカテーテルアブレーションとTCPC conversionが奏功した1例

森本芳正, 西井伸洋, 水野智文, 浅田早央莉, 木村朋生, 宮本真和, 中川晃志, 渡邊敦之, 中村一文, 伊藤　浩, 栄徳隆裕, 笠原真悟

日本成人先天性心疾患学会雑誌 9 ( 1 ) 247 2020.1

Fontan術後の複数の心房頻拍に対しRhythmiaによるカテーテルアブレーションとTCPC conversionが奏功した1例

森本芳正, 西井伸洋, 水野智文, 浅田早央莉, 木村朋生, 宮本真和, 中川晃志, 渡邊敦之, 中村一文, 伊藤浩, 栄徳隆裕, 笠原真悟

日本成人先天性心疾患学会雑誌 9 ( 1 ) 247 - 247 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

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

EP Europace 21 ( 11 ) 1663 - 1669 2019.11

Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

<title>Abstract</title>
<sec>
<title>Aims</title>
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.

</sec>
<sec>
<title>Methods and results</title>
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].

</sec>
<sec>
<title>Conclusion</title>
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.

</sec>

DOI： 10.1093/europace/euz207

Liver transplantation in a patient with hereditary haemorrhagic telangiectasia and pulmonary hypertension

Kentaro Ejiri, Satoshi Akagi, Kazufumi Nakamura, Naofumi Amioka, Keishi Ichikawa, Takahito Yagi, Hiroshi Ito

Pulmonary Circulation 9 ( 4 ) 2019.10

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications Ltd

Hereditary haemorrhagic telangiectasia or Rendu-Osler-Weber syndrome is a systemic vascular disease with autosomal dominant inheritance, mucocutaneous telangiectasia, and repeated nasal bleeding due to vascular abnormalities. Hereditary haemorrhagic telangiectasia may occasionally lead to complications, including arteriovenous malformations and pulmonary hypertension. We present a case of a 52-year-old female patient with hereditary haemorrhagic telangiectasia who was referred to our hospital for treatment of pulmonary hypertension. She had been diagnosed with hereditary haemorrhagic telangiectasia during adolescence and was being followed up. Six months prior to presentation, she had undergone coil embolization for pulmonary haemorrhage due to pulmonary arteriovenous malformations. She was in World Health Organization functional class IV, with a mean of pulmonary arterial pressure of 38 mmHg, a pulmonary capillary wedge pressure of 10 mmHg, and a right atrial pressure of 22 mmHg. A contrast-enhanced computed tomography angiography showed large arteriovenous malformations in the liver. Right heart catheterization revealed an increase in oxygen saturation in the inferior vena cava between the supra- and infra-hepatic veins, low pulmonary vascular resistance, and high right atrial pressure. Hence, she was diagnosed with hereditary haemorrhagic telangiectasia with pulmonary hypertension due to major arteriovenous shunt resulting from arteriovenous malformations in the liver. Therefore, we considered liver transplantation as an essential treatment option. She underwent cadaveric liver transplantation after a year resulting in dramatic haemodynamic improvement to World Health Organization functional class I. Liver transplantation is a promising treatment in patients with hereditary haemorrhagic telangiectasia and pulmonary hypertension resulting from arteriovenous shunt caused by arteriovenous malformations in the liver.

DOI： 10.1177/2045894019896677

遺残坐骨動脈瘤に対しステントグラフト(VIABAHN)を用いて治療した一例 Reviewed

大塚寛昭, 戸田洋伸, 江尻健太郎, 杜徳尚, 三好亨, 中村一文, 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 [MP34 - 006] 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. Reviewed

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

Inhibitory Effects of Tofogliflozin on Cardiac Hypertrophy in Dahl Salt-Sensitive and Salt-Resistant Rats Fed a High-Fat Diet.

Tomonari Kimura, Kazufumi Nakamura, Toru Miyoshi, Masashi Yoshida, Kaoru Akazawa, Yukihiro Saito, Satoshi Akagi, Yuko Ohno, Megumi Kondo, Daiji Miura, Jun Wada, Hiroshi Ito

International heart journal 60 ( 3 ) 728 - 735 2019.5

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

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are drugs for diabetes and might prevent heart failure. In this study, we investigated the effects of tofogliflozin, an SGLT2 inhibitor, on cardiac hypertrophy and metabolism in hypertensive rats fed a high-fat diet. Dahl salt-sensitive (DS) rats, hypertensive model rats, and Dahl salt-resistant (DR) rats, non-hypertensive model rats, were fed a high-salt and high-fat diet containing tofogliflozin (0.005%) for 9 weeks to examine the effects of this drug on cardiac hypertrophy and metabolism. Tofogliflozin tended to suppress a rise of the systolic blood pressure, relative to the control, throughout the treatment period in both DR and DS rats, and significantly suppress a rise of the systolic blood pressure, relative to the control, at the 9th week in DS rats. Tofogliflozin reduced cardiac hypertrophy (heart weight/body weight) not only in DS rats but also in DR rats. Histological analysis showed that tofogliflozin significantly decreased cardiomyocyte hypertrophy and perivascular fibrosis in both DS and DR rats. Tofogliflozin significantly decreased the expression levels of genes related to cardiac hypertrophy (encoding for natriuretic peptides A and B and interleukin-6), and to cardiac fibrosis (encoding for transforming growth factor-β1 and collagen type IV), in DS rats. Recent studies have shown that hypertrophied and failing hearts shift to oxidizing ketone bodies as a significant fuel source. We also performed metabolome analysis for ventricular myocardial tissue. Tofogliflozin reduced 3-hydroxybutyrate, a ketone body, and significantly decreased the expression levels of β-hydroxybutyrate dehydrogenase 1 and 3-oxoacid CoA-transferase, which are related to ketone oxidization. In conclusion, tofogliflozin ameliorated cardiac hypertrophy and fibrosis along with reduction of ketone usage in myocardial tissue.

DOI： 10.1536/ihj.18-392

The optimal amount of salt intake. International journal

Kazufumi Nakamura, Toru Miyoshi

Hypertension research : official journal of the Japanese Society of Hypertension 42 ( 5 ) 752 - 753 2019.5

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

Improvement of lung function and pulmonary hypertension after pulmonary aneurysm repair: case series

Satoshi Akagi, Kentaro Ejiri, Shingo Kasahara, Kazufumi Nakamura, Hiroshi Ito

Pulmonary Circulation 9 ( 1 ) 2019.1

Language：English Publishing type：Research paper (scientific journal) Publisher：SAGE Publications Ltd

Pulmonary artery aneurysms (PAA) can be complicated with pulmonary arterial hypertension (PAH), causing sudden death due to PA rupture and dissection. Because treatment with PAH-targeted drugs does not always prevent PAA progression, prophylactic surgical repair of the PAA seems a promising alternative. However, although it avoids rupture and dissection of the PAs, additional benefits have not been forthcoming. We therefore present two patients with co-existing PAH and a PAA who underwent surgical repair of the aneurysm. Following the surgery, their lung function and pulmonary hypertension improved. Optimal treatment of PAA remains uncertain, however, with no clear guidelines regarding the best therapeutic approach. This case series provides physicians with reasons to repair PAA surgically in patients with PAH.

DOI： 10.1177/2045894019831217

Japanese Antibacterial Drug Management for Cardiac Sarcoidosis (J-ACNES): A multicenter, open-label, randomized, controlled study. Reviewed

Kohei Ishibashi, Yoshinobu Eishi, Nobuhiro Tahara, Masanori Asakura, Naka Sakamoto, Kazufumi Nakamura, Yoichi Takaya, Tomohisa Nakamura, Yoshikazu Yazaki, Tetsuo Yamaguchi, Koko Asakura, Toshihisa Anzai, Teruo Noguchi, Satoshi Yasuda, Fumio Terasaki, Toshimitsu Hamasaki, Kengo Kusano

Journal of arrhythmia 34 ( 5 ) 520 - 526 2018.10

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

Background: Cardiac sarcoidosis (CS) is a noncaseating granulomatous disease of unknown etiology. Lifelong immunosuppressive therapy, most frequently using corticosteroids, is a standard therapy to control hypersensitivity of immune reactions and prevent inflammation. However, it sometimes causes various systemic adverse effects and requires dose escalation. Thus, additional therapy may be required for the treatment of this disease. Recently, Propionibacterium acnes (P. acnes) was reported as one of the etiologic agents of CS, indicating that antibacterial drugs (ABD) may be effective for the treatment of CS. The objective of this study was to investigate the effect of ABD treatment, in addition to standard corticosteroid therapy, in patients with CS. Methods: The Japanese Antibacterial Drug Management for Cardiac Sarcoidosis (J-ACNES) trial was designed as a prospective, multicenter, randomized, open-label, controlled clinical trial. The patients will be randomized to receive either standard corticosteroid therapy plus ABD therapy (ABD group) or standard corticosteroid therapy (standard group). The primary endpoint is change in the total standardized uptake value at 6 months vs baseline using fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography. Secondary endpoints include efficacy, prognosis, and safety. Results: The results of this study are currently under investigation. Conclusion: The J-ACNES trial will be the first prospective study assessing the clinical benefit and safety of ABD therapy, in addition to corticosteroid treatment, in patients with CS. Our findings may improve treatment of patients with CS, as additional ABD therapy reduces recurrence of inflammation and elucidates the mechanism of sarcoidosis.

DOI： 10.1002/joa3.12084

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

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

重度低心機能患者に発症した重症下肢虚血、糖尿病性壊疽に対し集学的治療を行った一例 Reviewed

大塚寛昭, 戸田洋伸, 江尻健太郎, 奥山倫弘, 大澤晋, 山田潔, 三好亨, 中村一文, 伊藤浩

日本下肢救済・足病学会誌 10 ( 1 ) 83 - 83 2018.6

High Baseline Lipoprotein(a) Level as a Risk Factor for Coronary Artery Calcification Progression: Sub-analysis of a Prospective Multicenter Trial.

Jun Ida, Kazuhiko Kotani, Toru Miyoshi, Kazufumi Nakamura, Kunihisa Kohno, Hirohiko Asonuma, Satoru Sakuragi, Masayuki Doi, Takashi Miki, Yasushi Koyama, Hiroshi Ito

Acta medica Okayama 72 ( 3 ) 223 - 230 2018.6

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

Lipoprotein(a), or Lp(a), is a low-density lipoprotein-like particle largely independent of known risk factors for, and predictive of, cardiovascular disease (CVD). We investigated the association between baseline Lp(a) levels and the progression of coronary artery calcification (CAC) in patients with hypercholesterolemia undergoing statin therapy. This study was a sub-analysis of a multicenter prospective study that evaluated the annual progression of CAC under intensive and standard pitavastatin treatment with or without eicosapentaenoic acid in patients with an Agatston score of 1 to 999, and hypercholesterolemia treated with statins. We classified the patients into 3 groups according to CAC progression. A total of 147 patients (mean age, 67 years; men, 54%) were analyzed. The proportion of patients with Lp(a) > 30 mg/dL significantly increased as CAC progressed (non-progression; 5.4%, 0<CAC progression ≦100; 7.7%, and CAC progression >100; 23.6%). Logistic regression analysis showed that Lp(a) > 30 mg/dL was an independent predictor of the annual change in Agatston score > 100 (OR: 5.51; 95% CI: 1.28-23.68; p=0.02), even after adjusting for age, sex, hypertension, diabetes mellitus, current smoking, body mass index, and lipid-lowering medications. Baseline Lp(a) >30 mg/dL was a predictor of CAC progression in this population of patients with hypercholesterolemia undergoing statin therapy.

DOI： 10.18926/AMO/56067

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

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

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

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. Reviewed

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

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

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

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

下肢動脈血栓塞栓症に対するEVTと外科的血栓除去の選択について Reviewed

戸田洋伸, 江尻健太郎, 大澤晋, 藤井泰宏, 武本梨佳, 内田治仁, 中村一文, 伊藤浩

脈管学 55 ( Suppl. ) S216 - S216 2015.10

Are beta-blockers effective or contraindicated in pulmonary arterial hypertension?

Kazufumi Nakamura, Hideki Fujio, Satoshi Akagi, Aya Miura, Toshihiro Sarashina, Nobuhiro Nishiand Hiroshi Ito

Recent Developments in Beta-Blockers Research 101 - 108 2015.4

Language：English Publishing type：Part of collection (book) Publisher：Nova Science Publishers, Inc.

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressively elevated pulmonary vascular resistance. Sustained elevation of pulmonary vascular resistance causes severe right ventricular hypertrophy and failure. Sympathetic nerve activity is increased in patients with left ventricular failure, and treatment with beta-adrenergic receptor blockers was found to improve survival rate and cardiac function of patients with left ventricular failure. Sympathetic nerve activity is also increased in patients with PAH. Muscle sympathetic nerve activity in patients with PAH was correlated with heart rate and NYHA class. These findings indicate that treatment with adrenergic receptor blockers may be effective in patients with PAH. However, neurohormonal modulation with beta-adrenergic receptor blockers carries the risks of decreased cardiac contractility and cardiac output. The safety of treatment with beta-adrenergic receptor blockers in clinical settings has been uncertain. Meanwhile, several experimental studies have shown beneficial effects of adrenergic receptor blockers in PAH. Carvedilol inhibited the exaggerated proliferation of pulmonary artery smooth muscle cells of patients with idiopathic PAH. Treatment with carvedilol improved survival of rats with monocrotaline-induced PAH. Bisoprolol also delays progression to right heart failure in rats with PAH. Careful use of beta blockers in selected patients might be beneficial. Further studies are needed to determine whether beta-adrenergic receptor blockers are tolerable and effective in patients with PAH.

Pioglitazone prevents the endothelial dysfunction induced by ischemia and reperfusion in healthy subjects. International journal

Yuka Sakatani, Toru Miyoshi, Hiroki Oe, Yoko Noda, Yuko Ohno, Kazufumi Nakamura, Yukihiro Saito, Kazuhiro Osawa, Hiroshi Morita, Kunihisa Kohno, Hiroshi Ito

Journal of cardiovascular pharmacology 64 ( 4 ) 326 - 31 2014.10

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

BACKGROUND: No study has investigated whether pioglitazone (an agonist of peroxisome proliferator-activated receptor gamma) protects against ischemia and reperfusion (IR)-induced endothelial dysfunction in humans. METHODS AND RESULTS: In the first crossover study, 20 volunteers were randomized to 1 week of pioglitazone (30 mg/d, postoperatively) or control (no treatment). In the second single-arm study, 15 volunteers received pioglitazone and the cyclooxygenase-2 inhibitor meloxicam for 1 week. On day 7, endothelium-dependent flow-mediated dilation (FMD) of the distal brachial artery was measured before and after IR (15 minutes of ischemia followed by 15 minutes of reperfusion in the proximal upper arm). Pre-IR brachial-artery diameter and FMD were similar across the 2 sessions (control, pioglitazone) in protocol 1 and between the 2 protocols. IR significantly blunted FMD after no treatment (pre-IR FMD: 10.2% ± 2.6%; post-IR FMD: 3.5% ± 1.9%, P < 0.01) but not after pioglitazone administration (pre-IR FMD: 9.7% ± 2.5%; post-IR FMD: 8.8% ± 2.9%, P = 0.11). This protective effect was accompanied by an increase in serum levels of the antioxidant enzyme extracellular superoxide dismutase and was not affected by concomitant administration of the cyclooxygenase-2 inhibitor meloxicam (P = 0.10). CONCLUSIONS: In humans, pioglitazone provides potent protection against IR-induced endothelial dysfunction.

DOI： 10.1097/FJC.0000000000000124

Omega-3 fatty acids improve postprandial lipemia and associated endothelial dysfunction in healthy individuals - a randomized cross-over trial. International journal

Toru Miyoshi, Yoko Noda, Yuko Ohno, Hiroki Sugiyama, Hiroki Oe, Kazufumi Nakamura, Kunihisa Kohno, Hiroshi Ito

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 68 ( 8 ) 1071 - 7 2014.10

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

BACKGROUND: Postprandial elevation of triglycerides impairs endothelial function and contributes to the development of atherosclerosis. We investigated the effects of omega-3 fatty acids on postprandial endothelial function and lipid profiles. METHODS: Healthy volunteers [10] were given supplementation at 4g/day omega-3 fatty acids (or were not treated) for 4 weeks in a randomised crossover study. Postprandial levels of various lipids were monitored and endothelial function assessed by brachial artery flow-mediated dilation during fasting and after a standard cookie test. RESULTS: Omega-3 fatty acids reduced postprandial endothelial dysfunction compared with the control diet (flow-mediated dilation at 4h=-0.5±1.2 vs. -2.0±1.6%, P=0.03). Postprandial levels of triglycerides, apolipoprotein B-48, and remnant lipoprotein-cholesterol increased in untreated subjects, peaked at 2-4h, and returned to baseline at 8h, whereas low-density lipoprotein-cholesterol levels did not change. Supplementation with omega-3 fatty acids significantly suppressed postprandial elevation of triglycerides (incremental area under the curve=220±209 vs. 374±216mg/h/dL, P=0.04) and remnant lipoprotein-cholesterol (incremental area under the curve=21.7±13.8 vs. 13.3±12.9mg/h/dL, P=0.04). Supplementation with omega-3 fatty acids significantly suppressed the increase in triglyceride content in chylomicrons as well as in very-low-density lipoproteins from baseline to 4h after the cookie test. CONCLUSION: Omega-3 fatty acids significantly decreased postprandial triglyceride elevation and postprandial endothelial dysfunction, suggesting that omega-3 fatty acids may have vascular protective effects in postprandial state.

DOI： 10.1016/j.biopha.2014.10.008

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)

心房中隔欠損症に対するカテーテル閉鎖術下大静脈縁の有無による治療成績の検討

木島康文, 赤木禎治, 中川晃志, 高谷陽一, 池田まどか, 渡辺修久, 麻植浩樹, 中村一文, 伊藤浩

超音波医学 41 ( Suppl. ) S715 - S715 2014.4

食道再建後の心房中隔欠損症に対してカテーテル閉鎖術を施行した一例

木島康文, 赤木禎治, 中川晃志, 高谷陽一, 池田まどか, 渡辺修久, 麻植浩樹, 中村一文, 伊藤浩

超音波医学 41 ( Suppl. ) S721 - S721 2014.4

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

卵円孔開存に対するAmplatzer PFO Occluderを用いたカテーテル閉鎖術

木島康文, 赤木禎治, 中川晃志, 高谷陽一, 上岡亮, 麻植浩樹, 中村一文, 佐野俊二, 伊藤浩

日本成人先天性心疾患学会雑誌 3 ( 1 ) 80 - 80 2014.1

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

An unsuccessful case of PAH-specific therapy in patient with pulmonary hypertension associated with ventricular septal defect

Akagi Satoshi, Sarashina Toshihiro, Kusano Kengo, Suzuki Hideyuki, Nakamura Kazufumi, Ito Hiroshi

Shinzo 46 ( 6 ) 812 - 815 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

うっ血性心不全に対するトルバプタンの効果予測因子に関する検討

戸田洋伸, 中村一文, 渡邊敦之, 中濱一, 寺坂律子, 草野研吾, 伊藤浩

日本心臓病学会誌 8 ( Suppl.I ) 299 - 299 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

PGI2経口薬をベースとした併用療法 PGI2(ベラプロスト)封入ナノ粒子吸入によるモノクロタリン誘発性肺高血圧の改善経口薬を吸入にする新たな試み

赤木達, 中村一文, 草野研吾, 伊藤浩

Therapeutic Research 34 ( 9 ) 1202 - 1202 2013.9

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

Serum cystatin C as a biomarker of cardiac diastolic dysfunction in patients with cardiac disease and preserved ejection fraction. Reviewed

Nosaka K, Nakamura K, Kusano K, Toh N, Tada T, Miyoshi T, Doi M, Kohno K, Morita H, Ito H

Congestive heart failure (Greenwich, Conn.) 19 ( 4 ) E35 - 9 2013.7

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

Safety and Efficacy of a Bolus Injection of Landiolol Hydrochloride as a Premedication for Multidetector-Row Computed Tomography Coronary Angiography

OSAWA Kazuhiro, MIYOSHI Toru, SATO Shuhei, AKAGI Noriaki, MORIMITSU Yusuke, NAKAMURA Kazufumi, KOHNO Kunihisa, KUSANO Kengo, KANAZAWA Susumu, ITO Hiroshi

JAPANESE CIRCULATION JOURNAL 77 ( 1 ) 146 - 152 2012.12

Language：English Publisher：The Japanese Circulation Society

Background: We evaluated the safety and efficacy of a bolus injection of landiolol hydrochloride, an ultrashort-acting β1-selective antagonist, as an additional treatment after premedication with an oral β-blocker to reduce heart rate prior to multidetector-row computed tomography (MDCT) coronary angiography (CAG). Methods and Results: A total of 458 patients who underwent MDCT CAG were retrospectively enrolled. Image quality and hemodynamic parameters were compared in patients before and after approval of landiolol hydrochloride. If heart rate reduction was insufficient after premedication with an oral β-blocker, a bolus injection of landiolol hydrochloride (n=66) or other drugs (n=30) was used. The percentage of evaluable images per segment in patients after approval of landiolol (99.3%) was greater than that in patients before approval of landiolol (97.4%, P<0.01). Heart rates before scanning in patients receiving landiolol hydrochloride were similar to those receiving other drugs. Heart rate was significantly reduced approximately 5min after injection of landiolol hydrochloride and increased shortly. No decrease in systolic blood pressure or other adverse effects was observed. Conclusions: Bolus injection of landiolol hydrochloride sufficiently reduced heart rate without significantly reducing systolic blood pressure and produced a high percentage of evaluable images, suggesting that bolus injection of landiolol hydrochloride as an additional pretreatment is feasible in MDCT CAG. (Circ J 2013; 77: 146–152)

DOI： 10.1253/circj.CJ-12-0663

CiNii Article

CiNii Books

Fragmented QRSは左心機能低下例で心機能改善の予測因子となる

Other Link： http://search.jamas.or.jp/link/ui/2013357873

[Oxidative stress and calcium overload in heart failure].

Kazufumi Nakamura, Daiji Miura, Hiromi Matsubara, Hiroshi Ito

Nihon yakurigaku zasshi. Folia pharmacologica Japonica 140 ( 6 ) 265 - 9 2012.12

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

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

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

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

冠動脈石灰化スコアは左室拡張不全のリスクマーカーとなるか?

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

日本心臓病学会誌 7 ( Suppl.I ) 361 - 361 2012.8

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

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

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

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

Guidelines for treatment of chronic heart failure

124 ( 1 ) 71 - 73 2012.4

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

プロスタグランジンI2はFasリガンドを介して特発性肺動脈性肺高血圧症患者の肺動脈平滑筋細胞のアポトーシスを誘導し肺血管リモデリングを改善する

赤木達, 中村一文, 草野研吾, 松原広己, 伊藤浩

日本臨床分子医学会学術総会プログラム・抄録集 49回 89 - 89 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。

Sustained monomorphic ventricular tachycardia in patients with Brugada syndrome

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

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

著明に拡張した肺動脈による左冠動脈主幹部狭窄をPCIにて治療しえた肺高血圧症の1例

赤木達, 中村一文, 内藤洋一郎, 草野研吾, 伊藤浩

Therapeutic Research 32 ( 10 ) 1217 - 1218 2011.10

Language：Japanese Publisher：ライフサイエンス出版(株)

56歳女。著明に拡張した主肺動脈が左冠動脈主幹部を圧排し、左冠動脈の血流低下が左心機能低下と肺高血圧症の悪化をもたらしていた。同部に対してIABP補助下に冠動脈ステント留置術を行い、肺高血圧の改善はあまりみられなかったが、左心機能の改善が得られた。

Other Link： https://search.jamas.or.jp/default/link?pub_year=2011&ichushi_jid=J01759&link_issn=&doc_id=20111111100004&doc_link_id=issn%3D0289-8020%26volume%3D32%26issue%3D10%26spage%3D1217&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0289-8020%26volume%3D32%26issue%3D10%26spage%3D1217&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

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

Nakamura K, Murakami M, Miura D, Yunoki K, Enko K, Tanaka M, Saito Y, Nishii N, Miyoshi T, Yoshida M, Oe H, Toh N, Nagase S, Kohno K, Morita H, Matsubara H, Kusano KF, Ohe T, Ito H

Pharmaceuticals (Basel, Switzerland) 4 ( 8 ) 1088 - 1100 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

糖尿病と心血管疾患拡張不全における糖代謝異常の関与

中村一文, 三好亨, 三浦大志, 麻植浩樹, 伊藤浩

日本心臓病学会誌 6 ( Suppl.I ) 167 - 167 2011.8

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)

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

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

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

Shinzo 43 ( 2 ) S2_39 - S2_45 2011

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

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

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

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

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

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

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)

Altered nano/micro-order elasticity of pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension Reviewed

Kazufumi Nakamura, Juichiro Shimizu, Noriyuki Kataoka, Katsushi Hashimoto, Tetsuya Ikeda, Hideki Fujio, Keiko Ohta-Ogo, Aiko Ogawa, Aya Miura, Satoshi Mohri, Satoshi Nagase, Hiroshi Morita, Kengo Fukushima Kusano, Hiroshi Date, Hiromi Matsubara, Seiichi Mochizuki, Ken Hashimoto, Fumihiko Kajiya, Tohru Ohe

International Journal of Cardiology 140 ( 1 ) 102 - 107 2010.4

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

Background: Idiopathic pulmonary arterial hypertension (IPAH) is a disease characterized by progressively increased resistance of pulmonary arteries. In this study, we evaluated the mechanical property of single pulmonary artery smooth muscles cells (PASMC) from patients with IPAH and tested whether the PASMC showed abnormal response to a vasodilator by use of an atomic force microscope (AFM). Methods: PASMC were isolated and cultured from explanted lungs of 7 patients with IPAH (IPAH-PASMC). Normal vascular specimens from 3 patients with bronchogenic carcinoma were used as normal controls (normal PASMC). The nano/micro-order elasticity of five to ten living PASMC in each sample was measured by parabolic force curves of cantilever deflection/indentation obtained by using an AFM. The elasticity measurements were performed under control conditions and under condition of nitric oxide (NO) treatment (190 and 380 nmol/L). Results: There was no significant difference between nano/micro-order elasticity of normal PASMC and that of IPAH-PASMC under the control conditions. In normal PASMC, NO (190 and 380 nmol/L) significantly reduced (i.e., softened) the nano/micro-order elasticity. However, NO did not reduce elasticity in IPAH-PASMC, indicating higher vasodilator-resistive nano/micro-order rigidity in IPAH-PASMC. Conclusion: Nano/micro-order elasticity change in PASMC in response to vasodilation induced by NO is reduced in patients with IPAH. © 2008 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2008.11.022

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

「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

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

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 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

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。

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

マイクロ空間構造付き細胞培養ディッシュを用いた新規マイグレーションアッセイ法の開発

西泰治, 三浦大志, 中村一文, 浦川茂美, 赤木達, 三浦綾, 草野研吾, 大江透, 菊池佑二

日本ヘモレオロジー学会プログラム・抄録集 16回 41 - 41 2009.11

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

非持続性心室頻拍を合併したacromegalic cardiomyopathyの1例

村上正人, 赤木達, 多田毅, 大郷恵子, 永瀬聡, 中村一文, 桜木悟, 草野研吾, 大江透

Journal of Cardiology 50 ( Suppl.I ) 501 - 501 2007.8

スプライシング供与部位に接する配列に変異を認めたQT延長症候群の一家系

赤木達, 中村一文, 福家聡一郎, 三浦大志, 永瀬聡, 桜木悟, 草野研吾, 大江透, 末丸俊二

Journal of Arrhythmia 23 ( Suppl. ) 304 - 304 2007.4

孤立性心筋緻密化障害を有する難治性心不全に対し両心室ペーシングが有用であった1例

中川晃志, 福家聡一郎, 西井伸洋, 永瀬聡, 中村一文, 櫻木悟, 草野研吾, 大江透, 飛岡徹

Journal of Arrhythmia 23 ( Suppl. ) 244 - 244 2007.4

Brugada症候群におけるNa遮断薬投与前後の体表面心電図と加算平均心電図の検討 SCN5A遺伝子での検討

渡辺敦之, 草野研吾, 永瀬聡, 三浦大志, 平松茂樹, 伴場主一, 西井伸洋, 中村一文, 桜木悟, 酒井芳明, 大江透

心臓 39 ( Suppl.1 ) 62 - 62 2007.2

SCN5A遺伝子のスプライシングドナーサイトに新規のmutationを認めたBrugada症候群の1例

三浦大志, 中村一文, 三浦綾, 平松茂樹, 渡邊敦之, 西井伸洋, 伴場主一, 谷山真規子, 木村英夫, 岩崎淳, 浦川茂美, 角田和歌子, 湯本晃久, 河野康之, 永瀬聡, 櫻木悟, 草野研吾, 大江透

心電図 26 ( 4 ) 500 - 500 2006.6

イオンチャネル異常による致死性不整脈 Brugada症候群におけるSCN5A遺伝子変異の臨床的意義

伴場主一, 永瀬聡, 三浦大志, 平松茂樹, 西井伸洋, 渡辺敦之, 中村一文, 櫻木悟, 酒井芳昭, 草野研吾, 大江透

心電図 26 ( 4 ) 408 - 408 2006.6

Andersen症候群の母子における各種薬剤負荷による心電図学的検討

永瀬聡, 西井伸洋, 伴場主一, 渡辺敦之, 平松茂樹, 酒井芳昭, 三浦大志, 三浦綾, 中村一文, 桜木悟, 草野研吾, 大江透

心電図 26 ( 4 ) 485 - 485 2006.6

SCN5A遺伝子のスプライシングドナーサイトに新規のmutationを認めたBrugada症候群の1例

Journal of Arrhythmia 22 ( Suppl. ) 244 - 244 2006.5

イオンチャネル異常による致死性不整脈 Brugada症候群におけるSCN5A遺伝子変異の臨床的意義

伴場主一, 永瀬聡, 三浦大志, 平松茂樹, 西井伸洋, 渡辺敦之, 中村一文, 桜木悟, 酒井芳昭, 草野研吾, 大江透

Journal of Arrhythmia 22 ( Suppl. ) 152 - 152 2006.5

Andersen症候群の母子における各種薬剤負荷による心電図学的検討

永瀬聡, 西井伸洋, 伴場主一, 渡辺敦之, 平松茂樹, 酒井芳昭, 三浦大志, 三浦綾, 中村一文, 桜木悟, 草野研吾, 大江透

Journal of Arrhythmia 22 ( Suppl. ) 229 - 229 2006.5

[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.

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

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

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

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.

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

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

心電図 24 ( 5 ) 293 - 293 2004.8

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.

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.