研究者基本情報

• 医学博士, 北海道大学大学院医学研究院, 2022年03月

• https://researchmap.jp/motoki_nakao

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=202101019254884851

• 90911694

• 202101019254884851

• バイオインフォマティクス
• 心不全
• 人工知能
• 光遺伝学
• 不整脈
• 心臓電気生理学

• ライフサイエンス, 循環器内科学
• ライフサイエンス, 生理学, 心臓電気生理学

研究活動情報

• 2025年10月, 日本心不全学会学術集会, Young Investigator’s Award 優秀賞
• 2024年09月, 日本心臓病学会, Young Investigator's Award（YIA）優秀賞
• 2024年03月, 日本循環器学会, Young Investigator’s Award Clinical Research部門 優秀賞
• 2013年11月, 日本循環器学会北海道地方会, Young Investigator’s Award 優秀賞

• Neuropeptide Y drives ventricular arrhythmogenesis in chronic ischemic heart failure via calcium mishandling.
  Jiro Koya; Taro Temma; Kei Kawakami; Fuyuki Karube; Zen-Ichi Tanei; Masahiro Kawasaki; Kintaro Shimano; Shota Saito; Daishiro Tatsuta; Kotaro Nishino; Hiroyuki Natsui; Takahide Kadosaka; Taro Koya; Motoki Nakao; Masaya Watanabe; Kiwamu Kamiya; Toshiyuki Nagai; Shinya Tanaka; Fumino Fujiyama; Toshihisa Anzai
  Heart rhythm, 22, 12, e1179-e1192, 2025年12月, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Ventricular arrhythmias (VAs) in chronic ischemic heart failure (HF) are associated with high mortality and often refractory to beta-blocker treatment, highlighting the need for alternative therapeutic targets. OBJECTIVE: This study investigates the role of neuropeptide Y (NPY), a neurotransmitter released during sympathoexcitation, in the pathogenesis of VAs associated with ischemic chronic HF following myocardial infarction (MI). METHODS: Using a mouse model of ischemic chronic HF after coronary ligation, we employed biochemical, electrophysiological, and calcium ion (Ca2+) imaging analyses to investigate the proarrhythmic mechanisms of NPY. RESULTS: Immunohistochemical staining revealed a significantly elevated NPY expression in both the MI and border zone, consistent with findings in human autopsy samples. In cardiomyocytes isolated from ischemic HF mice, NPY treatment increased Ca2+ waves at a dose that did not elicit this response in normal heart cardiomyocytes, an effect suppressed by NPY Y1 receptor blocker. Additionally, the NPY treatment elevated the frequency of delayed afterdepolarizations at the membrane potential level. Similarly, NPY-induced VAs that were suppressed by the NPY Y1 receptor blocker in Langendorff-perfused chronic ischemic failed hearts at a concentration that had no effect in normal hearts. CONCLUSION: We identified structural and functional changes in NPY within an chronic ischemic HF model, leading to increased arrhythmogenicity through Ca2+ mishandling. Therefore, targeting NPY signaling may offer a novel therapeutic approach for treating VAs in patients with chronic ischemic HF.
• Impact of Statement-Concordant Implantable Cardioverter-Defibrillator Programming on Therapy Reduction in an Asian Cohort.
  Jiro Koya; Taro Temma; Kei Kawakami; Masahiro Kawasaki; Kintaro Shimano; Shota Saito; Daishiro Tatsuta; Kotaro Nishino; Takahide Kadosaka; Taro Koya; Motoki Nakao; Masaya Watanabe; Kiwamu Kamiya; Toshiyuki Nagai; Toshihisa Anzai
  JACC. Asia, 2025年09月08日, ［国際誌］
  英語, 研究論文（学術雑誌）
• Battery Longevity in Modern Implantable Cardioverter-Defibrillators and Cardiac Resynchronization Therapy-Defibrillators.
  Kotaro Nishino; Taro Temma; Masaya Watanabe; Motoki Nakao; Masahiro Kawasaki; Kintaro Shimano; Kei Kawakami; Shota Saito; Jiro Koya; Daishiro Tatsuta; Hiroyuki Natsui; Takuya Koizumi; Takahide Kadosaka; Taro Koya; Kiwamu Kamiya; Toshiyuki Nagai; Toshihisa Anzai
  Journal of arrhythmia, 41, 4, e70175, 2025年08月, ［国内誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Battery longevity in high-voltage devices (HVDs), specifically implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy-defibrillators (CRT-Ds), is critical for reducing the frequency of generator replacements, minimizing procedural risks, and enhancing patient outcomes. Despite technological advancements, significant variability in battery performance remains among the major manufacturers. This study aimed to evaluate the battery longevity among ICDs and CRT-Ds from the major manufacturers implanted at a single institution and identify the factors influencing battery depletion. METHODS: We conducted a retrospective analysis of 353 patients implanted with HVDs (63 Abbott, 150 Boston Scientific, 140 Medtronic) at Hokkaido University Hospital between 2012 and 2021. Kaplan-Meier curves and Cox proportional hazards models were used to analyze the device longevity, with a primary endpoint of the time to battery depletion, defined by the elective replacement indicator. A multivariate analysis adjusted for the potential confounders. RESULTS: Boston Scientific devices exhibited a significantly longer battery life than Abbott and Medtronic devices (p < 0.001), with a 6-year replacement-free survival of 99% for ICDs and 93% for CRT-Ds. A multivariate analysis identified the device manufacturer, device type (ICD vs. CRT-D), and ventricular pacing rate as independent predictors of battery depletion (p < 0.001). CONCLUSION: Battery longevity differed significantly by the manufacturer, which may influence device selection. Devices with a longer battery life may help reduce the replacement frequency and could potentially contribute to improved patient outcomes and cost-effectiveness.
• Clinical Phenotyping and Treatment Response in Patients With Chronic Heart Failure
  Daishiro Tatsuta; Motoki Nakao; Toshiyuki Nagai; Yoshifumi Mizuguchi; Isao Yokota; Taro Koya; Atsushi Tada; Suguru Ishizaka; Fusako George; Yoshiya Kato; Shogo Imagawa; Ko Motoi; Yusuke Tokuda; Masashige Takahashi; Junichi Matsumoto; Masaharu Machida; Hiroshi Okamoto; Takahiko Saito; Toshihisa Anzai
  JACC: Advances, 4, 8, 101972, 101972, Elsevier BV, 2025年08月, ［査読有り］, ［筆頭著者］
  研究論文（学術雑誌）
• Serum Vasoactive Intestinal Peptide as a Novel Biomarker for Low-Voltage Areas in Patients With Atrial Fibrillation.
  Kotaro Nishino; Taro Temma; Hiroyuki Natsui; Masaya Watanabe; Motoki Nakao; Masahiro Kawasaki; Kintaro Shimano; Kei Kawakami; Shota Saito; Jiro Koya; Daishiro Tatsuta; Takuya Koizumi; Takahide Kadosaka; Taro Koya; Satonori Tsuneta; Kiwamu Kamiya; Toshiyuki Nagai; Toshihisa Anzai
  Journal of the American Heart Association, 14, 7, e039192, 2025年04月, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Low-voltage areas in the left atrium predict atrial fibrillation recurrence after catheter ablation and are associated with adverse outcomes like death, heart failure, and stroke. Detecting low-voltage areas (LVAs) typically requires invasive procedures, highlighting the need for a simple, minimally invasive marker. Vasoactive intestinal peptide (VIP), a neuropeptide released during parasympathetic stimulation, affects electrophysiological remodeling in atrial fibrillation. We hypothesized that serum VIP could serve as a biomarker for detecting LVAs in these patients. METHODS AND RESULTS: This prospective, cross-sectional study was conducted at Hokkaido University Hospital between August 2021 and September 2023. We included 108 patients with atrial fibrillation scheduled for catheter ablation. Blood samples were collected during ablation to measure VIP using an ELISA. Electroanatomical mapping identified LVAs, defined as regions with bipolar voltage ≤0.5 mV and occupying >5% of the left atrial surface. Statistical analyses evaluated the relationship between VIP and LVAs. Fifty-one patients (47%) had LVAs, with significantly higher serum VIP levels than those without (335.1 versus 247.7 pg/mL, P<0.001). VIP levels and female sex were statistically significant factors of LVAs. Adding VIP to the existing score significantly improved its discrimination (area under the curve: 0.784 versus 0.707, P<0.001). CONCLUSIONS: Serum VIP levels are higher in patients with atrial fibrillation with LVAs, suggesting its potential as a noninvasive biomarker for detecting these areas and improving clinical management.
• Prognostic Value of Reticulocyte Production Ability in Patients with Chronic Heart Failure.
  Motoki Nakao; Toshiyuki Nagai; Atsushi Tada; Taro Koya; Suguru Ishizaka; Yoshifumi Mizuguchi; Fusako George; Yoshiya Kato; Shogo Imagawa; Yusuke Tokuda; Masashige Takahashi; Junichi Matsumoto; Ko Motoi; Hiroshi Okamoto; Masaharu Machida; Takahiko Saito; Toshihisa Anzai
  The Canadian journal of cardiology, 2025年02月07日, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Anemia is frequently observed and associated with mortality in patients with heart failure (HF). Although the quality of erythropoiesis is an intrinsic aspect of anemia's pathophysiology, its prognostic value in HF patients is unclear. METHODS: Between January 2020 and October 2023, 1,328 symptomatic patients with chronic HF from a multicenter registry were prospectively examined. The reticulocyte production ability was evaluated by calculating the reticulocyte production index (RPI) using reticulocyte counts and serum hematocrit level. Patients were divided into four groups based on the presence or absence of anemia and the median RPI. The primary outcome was a composite of all-cause death and hospitalization for worsening HF. RESULTS: During a median follow-up of 551 (interquartile range 321-712) days, the primary outcome occurred in 219 patients. The incidence of the primary outcome was high among patients in the anemia and higher RPI group (≥ 0.978) (P <0.001). Higher RPI was independently associated with a higher risk of the primary outcome, even after adjusting for prognostic covariates (adjusted HR 1.37; 95% CI 1.05-1.78). Erythrocyte counts were significantly higher in patients with higher RPI in the groups without anemia (P <0.001); however, no significant differences were observed between the groups with anemia (P = 0.923). Serum iron levels and transferrin saturation did not significantly differ between the RPI groups with or without anemia. CONCLUSIONS: Higher RPI, which may reflect impaired maturation or a shortened lifespan of erythrocytes, was associated with worse clinical outcomes in HF patients irrespective of iron status.
• Enveloped Ablation: A Strategy for Managing Outflow Tract PVCs With an R Wave Pattern Break in Lead V2.
  Jiro Koya; Taro Temma; Motoki Nakao; Masaya Watanabe; Toshihisa Anzai
  Case reports in cardiology, 2025, 4667457, 4667457, 2025年, ［国際誌］
  英語, 研究論文（学術雑誌）, Outflow tract premature ventricular contractions (OT-PVCs) with an R wave pattern break in Lead V2 (PBV2) pose significant treatment challenges due to their refractory nature and complex anatomical origins. A 56-year-old male with drug-resistant palpitations underwent detailed electroanatomical mapping using a microcatheter to identify the earliest activation site. This precision mapping was crucial for directing the ablation strategy accurately. The "enveloped ablation" technique was employed, involving multisite, low-power ablations surrounding the critical activation site, tailored to address the unique electrical and structural characteristics of OT-PVCs with a PBV2. This case highlights the importance of accurate mapping and tailored ablation strategies in managing OT-PVCs with PBV2.
• Usefulness of frailty assessment using the revised Japanese version of the Cardiovascular Health Study on the prediction of clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.
  Takahiro Abe; Toshiyuki Nagai; Atsunori Yuasa; Yusuke Tokuda; Suguru Ishizaka; Sakae Takenaka; Yoshifumi Mizuguchi; Motoki Nakao; Takuma Sato; Taro Temma; Kiwamu Kamiya; Toshihisa Anzai
  Cardiovascular intervention and therapeutics, 40, 1, 144, 151, 2025年01月, ［国内誌］
  英語, 研究論文（学術雑誌）, Frailty assessment is essential for deciding the treatment strategy for patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Recently, the revised Japanese version of the Cardiovascular Health Study (J-CHS) criteria has been proposed for the frailty assessment; however, it is unclear whether the criteria are useful for the risk stratification in these patients. We investigated the impact of frailty assessment using the revised J-CHS criteria on clinical outcomes in patients with AS undergoing TAVR. We examined 205 consecutive severe AS patients who underwent TAVR at two tertiary hospitals from May 2018 to December 2022. Frailty was defined by the revised J-CHS criteria (score ≥ 3) before TAVR. The primary outcome was major adverse cardiac or cerebrovascular events (MACCE). Among the studied patients, the mean age was 84 years and 65% were female. Frailty was present in 51% of patients. During a median follow-up period of 1000 (interquartile range 677-1210) days, MACCE occurred in 22 patients. Frailty was significantly independently associated with higher risks of the MACCE adjusted for confounders related to nutritional status, severity of AS, comorbidities [hazard ratio (HR) 5.09, 95% confidence interval (CI) 1.70-15.23; HR 3.94, 95% CI 1.34-11.55; HR 3.12, 95% CI 1.14-8.53; HR 3.31, 95% CI 1.21-9.02, respectively]. Frailty determined by the revised J-CHS criteria was associated with clinical outcomes, suggesting these criteria would be useful for risk stratification in Japanese patients with AS undergoing TAVR.
• Normalization of increasing shocking coil impedance with full output synchronized shock.
  Takahide Kadosaka; Masaya Watanabe; Motoki Nakao; Taro Koya; Taro Temma; Toshihisa Anzai
  Journal of cardiovascular electrophysiology, 35, 11, 2251, 2253, 2024年08月21日, ［国際誌］
  英語, 研究論文（学術雑誌）, INTRODUCTION: Impedance is a crucial parameter in cardiovascular implantable electronic devices (CIEDs). Clinically, most CIEDs measure impedance using low voltage sub-threshold measurement (LVSM). Although the LVSM of shock impedance (LVSM-SI) is generally comparable with high voltage shock impedance (HVSI), LVSM-SI might be inaccurate if peri-lead tissue degeneration occurs. METHODS AND RESULTS: We present a case of elevated LVSM-SI occurring 8 years post-lead implantation, possibly attributed to encapsulation of the right ventricular lead coil. After 0.1 J shock was delivered, a full output synchronized shock was administered to measure HVSI, revealing a normal value. Furthermore, LVSM-SI was normalized and maintained within the normal range during long-term follow-up. CONCLUSION: Our findings suggest conducting a full-output synchronized shock test to assess HVSI when abnormal LVSM-SI is detected in the remote phase post-ICD implantation, which may be considered to help normalize LVSM shock impedance.
• Differential impacts of self-care behavior on clinical outcomes in patients with and without recent heart failure hospitalization.
  Taro Koya; Toshiyuki Nagai; Atsushi Tada; Motoki Nakao; Suguru Ishizaka; Yoshifumi Mizuguchi; Hiroyuki Aoyagi; Fusako George; Shogo Imagawa; Yusuke Tokuda; Yoshiya Kato; Masashige Takahashi; Hiroto Sakai; Masaharu Machida; Kenichi Matsutani; Takahiko Saito; Hiroshi Okamoto; Toshihisa Anzai
  International journal of cardiology, 415, 132452, 132452, 2024年08月14日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Although clinical guidelines recommend self-care assessment for patients with chronic heart failure (CHF), its prognostic significance remains controversial. This study aimed to compare the prognostic significance of self-care behavior on mortality between patients with and without a history of recent hospitalization for heart failure (HF). METHODS: We analyzed consecutive 1907 CHF patients from a Japanese multicenter registry (January 2020-June 2023) using the 9-item European Heart Failure Self-care Behavior Scale (EHFScBS-9) at enrolment. Suboptimal self-care behavior was defined as a score < 70 on the EHFScBS-9. Patients were divided into recent (within 30 days post-discharge, n = 664) and no recent hospitalization for HF groups (n = 1263), respectively. The primary outcome was a composite of all-cause death and rehospitalization for HF. RESULTS: During a median follow-up period of 427 (interquartile range 273-630) days, the primary outcome occurred in 100 patients. Patients with suboptimal self-care behavior exhibited a higher incidence of the primary outcome in the recent hospitalization for HF group (p = 0.020) but not in the no recent hospitalization for HF group (P = 0.16). Multivariable regressions showed suboptimal self-care behavior was independently associated with the primary outcome in the recent hospitalization for HF group with a significant interaction (P = 0.029). CONCLUSION: In patients recently hospitalized for HF, but not in those without a recent hospitalization history for HF, suboptimal self-care behavior was associated with adverse events. This indicates the importance of self-care education for these patients.
• Iron supplementation is a residual piece of management in Asian patients with heart failure?
  Motoki Nakao; Toshiyuki Nagai; Toshihisa Anzai
  International Journal of Cardiology, 132014, 132014, Elsevier BV, 2024年04月, ［招待有り］, ［筆頭著者］
  研究論文（学術雑誌）
• Influence of epicardial adipose tissue inflammation and adipocyte size on postoperative atrial fibrillation in patients after cardiovascular surgery
  Hiroyuki Natsui; Masaya Watanabe; Takashi Yokota; Satonori Tsuneta; Yoshizuki Fumoto; Haruka Handa; Matsushima Shouji; Jiro Koya; Kotaro Nishino; Daishiro Tatsuta; Takuya Koizumi; Takahide Kadosaka; Motoki Nakao; Taro Koya; Taro Temma; Yoichi M. Ito; Hatanaka C. Kanako; Yutaka Hatanaka; Shingu Yasushige; Satoru Wakasa; Shuhei Miura; Takahiko Masuda; Naritomo Nishioka; Shuichi Naraoka; Kayoko Ochi; Tomoko Kudo; Tsugumine Ishikawa; Toshihisa Anzai
  Physiological Reports, 12, 6, e15957, Wiley, 2024年03月28日, ［国際誌］
  英語, 研究論文（学術雑誌）, Abstract
  
  Epicardial adipose tissue (EAT) is an active endocrine organ that is closely associated with occurrence of atrial fibrillation (AF). However, the role of EAT in the development of postoperative AF (POAF) remains unclear. We aimed to investigate the association between EAT profile and POAF occurrence in patients who underwent cardiovascular surgery. We obtained EAT samples from 53 patients to evaluate gene expression, histological changes, mitochondrial oxidative phosphorylation (OXPHOS) capacity in the EAT, and protein secretion in EAT‐conditioned medium. EAT volume was measured using computed tomography scan. Eighteen patients (34%) experienced POAF within 7 days after surgery. Although no significant difference was observed in EAT profile between patients with and without POAF, logistic regression analysis identified that the mRNA expression levels of tumor necrosis factor‐alpha (TNF‐α) were positively correlated and adipocyte size in the EAT was inversely correlated with onset of POAF, respectively. Mitochondrial OXPHOS capacity in the EAT was not associated with POAF occurrence; however, it showed an inverse correlation with adipocyte size and a positive correlation with adiponectin secretion. In conclusion, changes in the secretory profile and adipocyte morphology of the EAT, which represent qualitative aspects of the adipose tissue, were present before the onset of AF.
• TAVRを受ける重症大動脈弁狭窄症患者のリスク層別化における改訂日本語版Cardiovascular Health Study基準(改訂J-CHS基準)の有用性(Usefulness of Revised Japanese Version of Cardiovascular Health Study for Risk Stratification in Patients with Severe Aortic Stenosis Undergoing TAVR)
  阿部 隆宏; 永井 利幸; 湯浅 敦智; 徳田 裕輔; 石坂 傑; 竹中 秀; 水口 賢史; 中尾 元基; 佐藤 琢真; 天満 太郎; 神谷 究; 安斉 俊久
  日本循環器学会学術集会抄録集, 88回, PJ017, 6, (一社)日本循環器学会, 2024年03月
  英語
• Machine Learning-based Gait Analysis to Predict Clinical Frailty Scale in Elderly Patients with Heart Failure
  Yoshifumi Mizuguchi; Motoki Nakao; Toshiyuki Nagai; Yuki Takahashi; Takahiro Abe; Shigeo Kakinoki; Shogo Imagawa; Kenichi Matsutani; Takahiko Saito; Masashige Takahashi; Yoshiya Kato; Hirokazu Komoriyama; Hikaru Hagiwara; Kenji Hirata; Takahiro Ogawa; Takuto Shimizu; Manabu Otsu; Kunihiro Chiyo; Toshihisa Anzai
  European Heart Journal - Digital Health, Oxford University Press (OUP), 2023年12月20日, ［査読有り］, ［筆頭著者］
  研究論文（学術雑誌）, Abstract
  
  Aims
  
  Although frailty assessment is recommended for guiding treatment strategies and outcome prediction in elderly patients with heart failure (HF), most frailty scales are subjective and the scores vary among raters. We sought to develop a machine learning-based automatic rating method/system/model of the clinical frailty scale (CFS) for patients with HF.
  
  Methods and Results
  
  We prospectively examined 417 elderly (≥75 years) with symptomatic chronic HF patients from seven centers between January 2019 and October 2023. The patients were divided into derivation (n = 194) and validation (n = 223) cohorts. We obtained body-tracking motion data using a deep learning-based pose estimation library, on a smartphone camera. Predicted CFS was calculated from 128 key features, including gait parameters, using the Light Gradient Boosting Machine (LightGBM) model. To evaluate the performance of this model, we calculated Cohen’s weighted kappa (CWK) and intraclass correlation coefficient (ICC) between the predicted and actual CFSs. In the derivation and validation datasets, the LightGBM models showed excellent agreements between the actual and predicted CFSs (CWK 0.866, 95% CI 0.807-0.911; ICC 0.866, 95% CI 0.827-0.898; CWK 0.812, 95% CI 0.752-0.868; ICC 0.813, 95% CI 0.761-0.854, respectively). During a median follow-up period of 391 (IQR 273-617) days, the higher predicted CFS was independently associated with a higher risk of all-cause death (HR 1.60, 95% CI 1.02-2.50) after adjusting for significant prognostic covariates.
  
  Conclusion
  
  Machine learning-based algorithms of automatically CFS rating are feasible, and the predicted CFS is associated with the risk of all-cause death in elderly patients with HF.
• 日本人高齢患者における植え込み型除細動器の有用性(Benefit of Implantable Cardioverter-defibrillator in Elderly Japanese Patients)
  甲谷 次郎; 天満 太郎; 立田 大志郎; 西野 広太郎; 夏井 宏征; 門坂 崇秀; 小泉 拓也; 甲谷 太郎; 中尾 元基; 渡邉 昌也; 安斉 俊久
  日本循環器学会学術集会抄録集, 87回, PJ113, 4, (一社)日本循環器学会, 2023年03月
  英語
• Optogenetic termination of atrial tachyarrhythmias by brief pulsed light stimulation
  Motoki Nakao; Masaya Watanabe; Lucile Miquerol; Hiroyuki Natsui; Takuya Koizumi; Takahide Kadosaka; Taro Koya; Hikaru Hagiwara; Rui Kamada; Taro Temma; Antoine A.F. de Vries; Toshihisa Anzai
  Journal of Molecular and Cellular Cardiology, Elsevier BV, 2023年03月, ［査読有り］, ［筆頭著者］
  研究論文（学術雑誌）
• Empagliflozin suppresses mitochondrial reactive oxygen species generation and mitigates the inducibility of atrial fibrillation in diabetic rats
  Takuya Koizumi; Masaya Watanabe; Takashi Yokota; Masumi Tsuda; Haruka Handa; Jiro Koya; Kotaro Nishino; Daishiro Tatsuta; Hiroyuki Natsui; Takahide Kadosaka; Taro Koya; Motoki Nakao; Hikaru Hagiwara; Rui Kamada; Taro Temma; Shinya Tanaka; Toshihisa Anzai
  Frontiers in Cardiovascular Medicine, 10, Frontiers Media SA, 2023年02月06日
  研究論文（学術雑誌）, Introduction
  
  Recent studies have demonstrated that sodium-glucose co-transporter-2 inhibitors (SGLT2-i) reduce the risk of atrial fibrillation (AF) in patients with diabetes mellitus (DM), in which oxidative stress due to increased reactive oxygen species (ROS) contributes to the pathogenesis of AF. We aimed to further investigate this, and examine whether the SGLT2-i empagliflozin suppresses mitochondrial-ROS generation and mitigates fibrosis.
  
  Methods
  
  A high-fat diet and low-dose streptozotocin treatment were used to induce type-2 DM (T2DM) in Sprague-Dawley rats. The rats were randomly divided into three groups: control, DM, and DM treated with empagliflozin (30 mg/kg/day) for 8 weeks. The mitochondrial respiratory capacity and ROS generation in the atrial myocardium were measured using a high-resolution respirometer. Oxidative stress markers and protein expression related to mitochondrial biogenesis and dynamics as well as the mitochondrial morphology were examined in the atrial tissue. Additionally, mitochondrial function was examined in H9c2 cardiomyoblasts. Atrial tachyarrhythmia (ATA) inducibility, interatrial conduction time (IACT), and fibrosis were also measured.
  
  Results
  
  Inducibility of ATA, fibrosis, and IACT were increased in rats with DM when compared to controls, all of which were restored by empagliflozin treatment. In addition, the rats with DM had increased mitochondrial-ROS with an impaired complex I-linked oxidative phosphorylation capacity. Importantly, empagliflozin seemed to ameliorate these impairments in mitochondrial function. Furthermore, empagliflozin reversed the decrease in phosphorylated AMPK expression and altered protein levels related to mitochondrial biogenesis and dynamics, and increased mitochondrial content. Empagliflozin also improved mitochondrial function in H9c2 cells cultured with high glucose medium.
  
  Discussion
  
  These data suggest that empagliflozin has a cardioprotective effect, at least in part, by reducing mitochondrial ROS generation through AMPK signaling pathways in the atrium of diabetic rats. This suggests that empagliflozin might suppress the development of AF in T2DM.
• Fragmented QRS on 12-lead electrocardiogram predicts long-term prognosis in patients with cardiac sarcoidosis.
  Hikaru Hagiwara; Masaya Watanabe; Takahide Kadosaka; Takuya Koizumi; Yuta Kobayashi; Taro Koya; Motoki Nakao; Satonori Tsuneta; Yoshiya Kato; Hirokazu Komoriyama; Rui Kamada; Toshiyuki Nagai; Kohsuke Kudo; Toshihisa Anzai
  Heart and vessels, 2023年01月13日, ［国内誌］
  英語, 研究論文（学術雑誌）, Fragmented QRS (fQRS) on a 12-lead electrocardiogram is a known marker of fatal arrhythmias or cardiac adverse events in ischemic and non-ischemic cardiomyopathy patients. Nonetheless, the association between fQRS and clinical outcomes in patients with cardiac sarcoidosis (CS) remains unclear. Herein, we investigated whether fQRS is associated with long-term clinical outcomes in CS patients. A total of 78 patients who received immunosuppressive therapy (IST) for clinically diagnosed CS were retrospectively examined. Patients were classified into two groups according to the presence (n = 19) or absence (n = 59) of fQRS on electrocardiogram before IST. The primary outcome was the composite event of all-cause death, ventricular tachyarrhythmias (VTs), and hospitalization for heart failure. Results of late gadolinium enhancement on cardiac magnetic resonance imaging were also analyzed. During a median follow-up period of 3.7 years (interquartile range: 1.6-6.2 years), the primary outcome occurred more frequently in patients with fQRS than in those without (47% vs. 13%, log-rank p = 0.002). Multivariable Cox regression analyses showed that fQRS was an independent determinant of the primary outcome. The incidence of VTs, within 12 months of IST initiation, was comparable between the two groups; however, late-onset VTs, defined as those occurring ≥ 12 months after IST initiation, occurred more frequently in the fQRS group (21% vs. 2%, log-rank p = 0.002). The scar zone and scar border zone were greater in patients with fQRS than in those without it. In conclusion, our analysis suggests that fQRS is an independent predictor of adverse events, particularly late-onset VTs, in patients with CS.
• Empagliflozin attenuates arrhythmogenesis in diabetic cardiomyopathy by normalizing intracellular Ca2+ handling in ventricular cardiomyocytes.
  Takahide Kadosaka; Masaya Watanabe; Hiroyuki Natsui; Takuya Koizumi; Motoki Nakao; Taro Koya; Hikaru Hagiwara; Rui Kamada; Taro Temma; Fuyuki Karube; Fumino Fujiyama; Toshihisa Anzai
  American journal of physiology. Heart and circulatory physiology, 324, 3, H341-H354, 2023年01月06日, ［国際誌］
  英語, 研究論文（学術雑誌）, Diabetic cardiomyopathy has been reported to increase the risk of fatal ventricular arrhythmia. The beneficial effects of the selective sodium-glucose co-transporter 2 inhibitor have not been fully examined in the context of anti-arrhythmic therapy, especially its direct cardioprotective effects despite the negligible SGLT2 expression in cardiomyocytes. We aimed to examine the anti-arrhythmic effects of empagliflozin (EMPA) treatment on diabetic cardiomyocytes, with a special focus on Ca2+ handling. We conducted echocardiography and hemodynamic studies and studied electrophysiology, Ca2+ handling, and protein expression in C57BLKS/J-leprdb/db mice (db/db mice) and their non-diabetic lean heterozygous Leprdb/+ littermates (db/+ mice). Preserved systolic function with diastolic dysfunction was observed in 16-week-old db/db mice. During arrhythmia induction, db/db mice had significantly increased premature ventricular complexes (PVCs) than controls, which was attenuated by EMPA. In protein expression analyses, calmodulin-dependent protein kinase II (CaMKII) Thr287 autophosphorylation and CaMKII-dependent RyR2 phosphorylation (S2814) were significantly increased in diabetic hearts, which were inhibited by EMPA. Additionally, global O-GlcNAcylation significantly decreased with EMPA treatment. Furthermore, EMPA significantly inhibited ventricular cardiomyocyte glucose uptake. Diabetic cardiomyocytes exhibited increased spontaneous Ca2+ events and decreased sarcoplasmic reticulum (SR) Ca2+ content, along with impaired Ca2+ transient, all of which normalized with EMPA treatment. Notably, most EMPA-induced improvements in Ca2+ handling were abolished by the addition of an O-GlcNAcase (OGA) inhibitor. In conclusion, EMPA attenuated ventricular arrhythmia inducibility by normalizing the intracellular Ca2+ handling, and we speculated that this effect was, at least partly, due to the inhibition of O-GlcNAcylation via the suppression of glucose uptake into cardiomyocytes.
• Applicability of new proposed criteria for iron deficiency in Japanese patients with heart failure.
  Atsushi Tada; Toshiyuki Nagai; Taro Koya; Motoki Nakao; Suguru Ishizaka; Yoshifumi Mizuguchi; Hiroyuki Aoyagi; Shogo Imagawa; Yusuke Tokuda; Masashige Takahashi; Yoshiya Kato; Masaharu Machida; Kenichi Matsutani; Takahiko Saito; Toshihisa Anzai
  ESC heart failure, 2022年12月10日, ［国際誌］
  英語, 研究論文（学術雑誌）, AIMS: Iron deficiency (ID) is a common co-morbidity in patients with heart failure (HF). A recent study showed that ID defined by the current guideline criteria was not associated with worse clinical outcomes, and new ID criteria was proposed in patients with HF. However, the external applicability of the new proposed criteria is unclear. We sought to investigate the applicability of the proposed ID criteria in Japanese patients with HF. METHODS AND RESULTS: We prospectively examined 763 patients with chronic HF from a Japanese multicentre registry. The proposed ID criteria were transferrin saturation (TSAT) < 20% and serum iron ≤13 mmol/L and the guideline ID criteria were serum ferritin <100 ng/mL or, when ferritin was 100-299 ng/mL, TSAT <20%. Among all patients (456 male, mean age 71 ± 13 years), 213 (28%) and 444 (58%) met the proposed and guideline ID criteria, respectively. During a median follow-up period of 436 days (interquartile range 297-565), the primary outcome of all-cause mortality occurred in 56 (7%) patients. There was no significant difference in the primary outcome between the patients with and without guideline ID criteria (P = 0.32), whereas patients with serum iron ≤10 μmol/L showed higher mortality (P = 0.002). In multivariable Cox regressions, the proposed ID criteria, but not guideline ID criteria, were independently associated with the risk of all-cause mortality (HR 2.01, 95% CI 1.16-3.51 and HR 1.32, 95% CI 0.76-2.28, respectively), even after adjustment for covariates. CONCLUSIONS: When defined by the proposed criteria and not the guideline criteria, ID was associated with higher mortality in patients with chronic HF, suggesting that the proposed ID criteria is applicable to the Japanese population.
• Pharmacological nNOS inhibition modified small-conductance Ca2+-activated K+ channel without altering Ca2+ dynamics.
  Taro Koya; Masaya Watanabe; Hiroyuki Natsui; Takahide Kadosaka; Takuya Koizumi; Motoki Nakao; Hikaru Hagiwara; Rui Kamada; Taro Temma; Toshihisa Anzai
  American journal of physiology. Heart and circulatory physiology, 323, 5, H869-H878, 2022年11月01日, ［国際誌］
  英語, 研究論文（学術雑誌）, Atrial fibrillation (AF) is associated with electrical remodeling processes that promote a substrate for the maintenance of AF. Although the small-conductance Ca2+-activated K+ (SK) channel is a key factor in atrial electrical remodeling, the mechanism of its activation remains unclear. Regional nitric oxide (NO) production by neuronal nitric oxide synthase (nNOS) is involved in atrial electrical remodeling. In this study, atrial tachyarrhythmia (ATA) induction and optical mapping were performed on perfused rat hearts. nNOS is pharmacologically inhibited by S-methylthiocitrulline (SMTC). The influence of the SK channel was examined using a specific channel inhibitor, apamin (APA). Parameters such as action potential duration (APD), conduction velocity, and calcium transient (CaT) were evaluated using voltage and calcium optical mapping. The dominant frequency was examined in the analysis of AF dynamics. SMTC (100 nM) increased the inducibility of ATA and apamin (100 nM) mitigated nNOS inhibition-induced arrhythmogenicity. SMTC caused abbreviations and enhanced the spatial dispersion of APD, which was reversed by apamin. By contrast, conduction velocity and other parameters associated with CaT were not affected by SMTC or apamin administration. Apamin reduced the frequency of SMTC-induced ATA. In summary, nNOS inhibition abbreviates APD by modifying the SK channels. A specific SK channel blocker, apamin, mitigated APD abbreviation without alteration of CaT, implying an underlying mechanism of posttranslational modification of SK channels.NEW & NOTEWORTHY We demonstrated that pharmacological nNOS inhibition increased the atrial arrhythmia inducibility and a specific small-conductance Ca2+-activated K+ channel blocker, apamin, reversed the enhanced atrial arrhythmia inducibility. Apamin mitigated APD abbreviation without alteration of Ca2+ transient, implying an underlying mechanism of posttranslational modification of SK channels.
• Predictors of cardiovascular mortality after an electrical storm in patients with structural heart disease.
  Takuya Koizumi; Rui Kamada; Masaya Watanabe; Hisashi Yokoshiki; Taro Temma; Hikaru Hagiwara; Taro Koya; Motoki Nakao; Takahide Kadosaka; Hiroyuki Natsui; Masayuki Takahashi; Kazuya Mizukami; Hirofumi Mitsuyama; Toshihisa Anzai
  Journal of cardiology, 80, 2, 167, 171, 2022年08月, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Electrical storms (ESs) in patients with structural heart disease (SHD) have been reported to be associated with a poor prognosis. However, the detailed cause of death and influence of implantable cardioverter defibrillator (ICD) therapy in ES patients have not been fully investigated. Therefore, we sought to explore the detailed clinical course after an ES and the impact of the ICD therapy in patients with SHDs. METHODS: We retrospectively analyzed 31 consecutive patients with ESs who had undergone an ICD implantation. ESs were defined as three or more ventricular arrhythmias within 24 h. RESULTS: During a mean follow up of 4.5 years, 13 patients died. Among them, cardiovascular death (CVD) was observed in 11/13 (85%), and the leading cause of the CVD was end-stage heart failure. A New York Heart Association class ≥III at the time of the ES occurrence (HR 6.51 95% CI 1.94-25.1, p = 0.003) and any shock therapy (HR 5.94 95% CI 1.06-112.2, p = 0.04) were associated with CVD. CONCLUSION: In the current single center study, the major cause of death in ES patients with SHDs was end-stage heart failure. Any shock therapy was associated with CVD. Arrhythmia management to avoid ICD shocks might reduce the mortality in ES patients.
• Stimulation of the mitochondrial calcium uniporter mitigates chronic heart failure-associated ventricular arrhythmia in mice.
  Hikaru Hagiwara; Masaya Watanabe; Yoichiro Fujioka; Takahide Kadosaka; Takuya Koizumi; Taro Koya; Motoki Nakao; Rui Kamada; Taro Temma; Kazufumi Okada; Jose Antonio Moreno; Ohyun Kwon; Hisakata Sabe; Yusuke Ohba; Toshihisa Anzai
  Heart rhythm, 19, 10, 1725, 1735, 2022年05月31日, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: An aberrant increase in the diastolic calcium concentration ([Ca2+]i) level is a hallmark of heart failure (HF) and the cause of delayed afterdepolarization and ventricular arrhythmia (VA). Although mitochondria play a role in regulating [Ca2+]i, whether they can compensate for the [Ca2+]i abnormality in ventricular myocytes is unknown. OBJECTIVE: We investigated whether enhanced Ca2+ uptake of mitochondria may compensate for an abnormal increase in the [Ca2+]i of ventricular myocytes in HF to effectively mitigate VA. METHODS: We used a HF mouse model, in which myocardial infarction was induced by permanent left anterior descending coronary artery ligation. The mitochondrial Ca2+ uniporter was stimulated by kaempferol. Ca2+ dynamics and membrane potential were measured using an epifluorescence microscope, a confocal microscope, and the perforated patch-clamp technique. VA was induced in the Langendorff-perfused hearts, and the hemodynamic parameters were measured using a microtip transducer catheter. RESULTS: Protein expression of the mitochondrial Ca2+ uniporter, as assessed by its subunit expression, did not change between HF and sham mice. Treatment of cardiomyocytes with kaempferol, isolated from HF mice at 28 days after coronary ligation, reduced the appearance of aberrant diastolic [Ca2+]i waves and sparks and spontaneous action potentials. Kaempferol effectively reduced the VA occurring in Langendorff-perfused hearts. Intravenous administration of kaempferol did not markedly affect the left ventricular hemodynamic parameters. CONCLUSION: The effects of kaempferol in HF of mice implied that mitochondria may have the potential to compensate for abnormal [Ca2+]i. Mechanisms involved in mitochondrial Ca2+ uptake may provide novel targets to treat HF-associated VA.
• Suppression of Mitochondrial Oxidative Stress and Atrial Fibrillation Inducibility by SGLT2 Inhibitors in Diabetic Rats(和訳中)
  小泉 拓也; 渡邉 昌也; 横田 卓; 夏井 宏征; 門坂 崇秀; 甲谷 太郎; 中尾 元基; 萩原 光; 鎌田 塁; 天満 太郎; 安斉 俊久
  日本循環器学会学術集会抄録集, 86回, MPJ14, 4, (一社)日本循環器学会, 2022年03月
  英語
• J-CLEAR通信 136)心不全の薬物治療-収縮機能障害HFrEFを中心として
  中尾元基; 安斉俊久
  週刊日本医事新報, 5096, 36, 40, (株)日本医事新報社, 2021年12月
  日本語
• 器質的心疾患患者における繰り返す心室頻拍後の心臓死規定因子の検討
  小泉 拓也; 鎌田 塁; 夏井 宏征; 門坂 崇秀; 中尾 元基; 甲谷 太郎; 萩原 光; 渡邉 昌也; 横式 尚司; 安斉 俊久
  日本心臓病学会学術集会抄録, 69回, O, 232, (一社)日本心臓病学会, 2021年09月
  日本語
• Hybrid epicardial ventricular tachycardia ablation with lateral thoracotomy in a patient with a history of left ventricular reconstruction surgery
  Taro Koya; Masaya Watanabe; Rui Kamada; Hikaru Hagiwara; Motoki Nakao; Takahide Kadosaka; Takuya Koizumi; Toshihisa Anzai
  Journal of Cardiology Cases, Elsevier BV, 2021年07月
  研究論文（学術雑誌）
• Intramural Tissueの二つの遅延伝導領域を交互に伝播することで維持されるリエントリーを機序とする交代性QRS波形を呈するVTを認めた非虚血性心筋症の1例
  鎌田 塁; 渡邉 昌也; 天満 太郎; 萩原 光; 甲谷 太郎; 中尾 元基; 安斉 俊久; 横式 尚司; 四倉 昭彦; 南部 忠詞; 吉田 泉; 櫻井 正之
  臨床心臓電気生理, 44, 183, 191, 臨床心臓電気生理研究会, 2021年05月
  日本語
• Epsilon wave disappearance by catheter ablation for ventricular arrhythmia from the left ventricular outflow tract.
  Hikaru Hagiwara; Masaya Watanabe; Rui Kamada; Taro Koya; Motoki Nakao; Toshihisa Anzai
  HeartRhythm case reports, 7, 5, 343, 346, 2021年05月, ［国際誌］
  英語
• Risk Stratification Towards Precision Medicine in Heart Failure - Current Progress and Future Perspectives.
  Toshiyuki Nagai; Motoki Nakao; Toshihisa Anzai
  Circulation journal : official journal of the Japanese Circulation Society, 85, 5, 576, 583, 2021年03月02日, ［国内誌］
  英語, 研究論文（学術雑誌）, Clinical risk stratification is a key strategy used to identify low- and high-risk subjects to optimize the management, ranging from pharmacological treatment to palliative care, of patients with heart failure (HF). Using statistical modeling techniques, many HF risk prediction models that combine predictors to assess the risk of specific endpoints, including death or worsening HF, have been developed. However, most risk prediction models have not been well-integrated into the clinical setting because of their inadequacy and diverse predictive performance. To improve the performance of such models, several factors, including optimal sampling and biomarkers, need to be considered when deriving the models; however, given the large heterogeneity of HF, the currently advocated one-size-fits-all approach is not appropriate for every patient. Recent advances in techniques to analyze biological "omics" information could allow for the development of a personalized medicine platform, and there is growing awareness that an integrated approach based on the concept of system biology may be an excessively naïve view of the multiple contributors and complexity of an individual's HF phenotype. This review article describes the progress in risk stratification strategies and perspectives of emerging precision medicine in the field of HF management.
• Higher Pulmonary Arterial Pressure Was Related to Non-Pulmonary Vein Atrial Tachyarrhythmia.
  Wei-Chieh Lee; Masaya Watanabe; Hisashi Yokoshiki; Taro Temma; Rui Kamada; Hikaru Hagiwara; Yumi Takahashi; Taro Koya; Motoki Nakao; Toshihisa Anzai
  International heart journal, 61, 6, 1150, 1156, 2020年11月28日, ［国内誌］
  英語, 研究論文（学術雑誌）, Recurrence of atrial tachyarrhythmias (ATA) following catheter ablation for atrial fibrillation (AF) is often associated with the recovery of conduction into previously isolated pulmonary veins (PVs). Little evidence concerning repeat PV isolation (PVI) and non-PV ATA ablation has been reported. This study aimed to explore the clinical outcome of recurrent ATA ablation after PVI and the difference between patients with and without non-PV ATA.A total of 49 patients without structural heart diseases who received catheter ablation for recurrent AF between January 2014 and December 2018 were recruited (prior ablation with PVI only 71.4% and PVI with cavotricuspid isthmus line ablation 28.6%). Patients were divided into two groups according to the presence or absence of non-PV ATA.Most patients (53.1%) experienced very late recurrence with a median duration of 15 months. A total of 15 patients had non-PV ATA and received non-PV ATA ablation whereas 34 patients received only repeat PVI for reconnected PVs. A higher pulmonary arterial systolic pressure (PASP) was associated with non-PV ATA (odds ratio: 1.161; 95% confidence interval: 1.021-1.321; P = 0.023). During 4.7 ± 1 months, 4/15 (26.7%) and 1/34 (2.9%) patients with and without non-PV ATA, respectively, had ATA recurrence (P = 0.011). The cumulative incidence of ATA recurrence after repeat ablation was significantly lower in patients without non-PV ATA (P = 0.013).In our study, a high PASP was associated with non-PV ATA in patients with recurrent AF. Repeat PVI had a high rate of maintenance of sinus rhythm in patients without non-PV ATA.
• 心臓サルコイドーシス患者でfragmented QRSは、心事故、慢性期致死性不整脈と関連する
  萩原 光; 渡邉 昌也; 中尾 元基; 甲谷 太郎; 小林 雄太; 加藤 喜哉; 小森山 弘和; 鎌田 塁; 永井 利幸; 安斉 俊久
  日本サルコイドーシス/肉芽腫性疾患学会雑誌, 40, サプリメント号, 56, 56, 日本サルコイドーシス, 2020年10月
  日本語
• Successful epicardial ablation for ventricular tachycardia originating from the true apex of apical aneurysm associated with hypertrophic cardiomyopathy
  Motoki Nakao; Masaya Watanabe; Rui Kamada; Hikaru Hagiwara; Yumi Takahashi; Taro Koya; Takahide Kadosaka; Takuya Koizumi; Masanori Hirose; Toshihisa Anzai
  JOURNAL OF ELECTROCARDIOLOGY, 61, 170, 174, 2020年07月
  英語, 研究論文（学術雑誌）
• Differential Prognostic Impact of Atrial Fibrillation in Hospitalized Heart Failure Patients With Preserved Ejection Fraction According to Coronary Artery Disease Status - Report From the Japanese Nationwide Multicenter Registry.
  Taro Temma; Toshiyuki Nagai; Masaya Watanabe; Rui Kamada; Yumi Takahashi; Hikaru Hagiwara; Taro Koya; Motoki Nakao; Kazunori Omote; Kiwamu Kamiya; Hiroyuki Iwano; Kazuhiro Yamamoto; Tsutomu Yoshikawa; Yoshihiko Saito; Toshihisa Anzai
  Circulation journal : official journal of the Japanese Circulation Society, 84, 3, 397, 403, 2020年02月25日, ［国内誌］
  英語, 研究論文（学術雑誌）, BACKGROUND: Atrial fibrillation (AF) is an important prognostic determinant in heart failure (HF) with preserved ejection fraction (HFpEF). However, it is unclear which HFpEF phenotypes are affected by AF in terms of long-term clinical outcomes because HFpEF is a heterogeneous syndrome with comorbidities such as coronary artery disease (CAD). In this study we determined the differential prognostic significance of AF in HFpEF patients according to CAD status.Methods and Results:Data for 408 hospitalized HFpEF patients enrolled in the Japanese Heart Failure Syndrome with Preserved Ejection Fraction Nationwide Multicenter Registry were analyzed. Patients were divided into 4 groups according to the presence of AF and CAD. The primary outcome was the composite of all-cause death and HF rehospitalization. The incidence of adverse events was higher in the AF-non-CAD than non-AF-non-CAD group (P=0.004). On multivariable Cox regression analysis with prespecified confounders, AF-non-CAD was significantly associated with an increased risk of adverse events than non-AF-non-CAD (adjusted HR, 1.91; 95% CI: 1.02-3.92) regardless of the type of AF. In contrast, risk was comparable between the AF-CAD and non-AF-CAD groups (adjusted HR, 1.24; 95% CI: 0.64-2.47). CONCLUSIONS: In HFpEF patients without CAD, AF was independently related to adverse events, indicating that intensive management of AF would have more beneficial effects particularly in HFpEF patients without CAD.
• Refractory Right Ventricular Failure in a Patient with Emery-Dreifuss Muscular Dystrophy
  Yasuyuki Chiba; Arata Fukushima; Motoki Nakao; Yuta Kobayashi; Takahiro Ishigaki; Taro Tenma; Kiwamu Kamiya; Yasushige Shingu; Tomonori Ooka; Yoshiro Matsui; Toshihisa Anzai
  INTERNAL MEDICINE, 59, 10, 1277, 1281, 2020年
  英語, 研究論文（学術雑誌）

• 房室結節近傍のreentrant型心房頻拍におけるpresystolic atrial potentialの意義
  川崎祐寛; 天満太郎; 中尾元基; 甲谷太郎; 門坂崇秀; 立田大志郎; 西野広太郎; 甲谷次郎; 齋藤翔太; 川上慧; 島野金太郎; 上原拓樹; 佐々木亮; 千葉裕基; 平子竜大; 伊藤仁弥; 安斉俊久, 日本不整脈心電学会カテーテルアブレーション関連大会(Web), 2025, 2025年
• HFrEF患者におけるmid-range QRS幅の自然予後
  齋藤翔太; 天満太郎; 永井利幸; 中尾元基; 甲谷太郎; 加藤喜哉; 今川正吾; 本居昂; 徳田裕輔; 高橋将成; 松本純一; 岡本洋; 町田正晴; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 17th, 2025年
• Decrement-Evoked Potential MappingによるFunctional Line of Blockの明瞭化とDecrement-Evoked Potentialの性状を活用した陳旧性心筋梗塞後心室頻拍における共通緩徐伝導路の推定
  天満太郎; 中尾元基; 門坂崇秀; 夏井宏征; 甲谷次郎; 西野広太郎; 立田大志郎; 斎藤翔太; 安斉俊久; 横式尚司; 渡邉昌也; 四倉昭彦; 吉田泉; 櫻井正之, 臨床心臓電気生理, 48, 2025年
• 植込み型除細動機能付きデバイス患者における自動車運転免許制限に関する調査
  千葉裕基; 天満太郎; 森倫子; 佐々木亮; 前野幹; 平子竜大; 伊藤仁弥; 立田大志郎; 甲谷次郎; 齋藤翔太; 西野広太郎; 門坂崇秀; 夏井宏征; 夏井宏征; 中尾元基; 甲谷太郎; 渡邉昌也; 渡邉昌也; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 17th, 2025年
• 植込み型除細動器のショック作動が心筋に与える影響の検討
  門坂崇秀; 渡邉昌也; 水上和也; 横式尚司; 島野金太郎; 川崎祐寛; 川上慧; 齋藤翔太; 西野広太郎; 甲谷次郎; 立田大志郎; 中尾元基; 甲谷太郎; 天満太郎; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 17th, 2025年
• 2機種のmapping systemにおけるDEEP mappingの検討
  平子竜大; 天満太郎; 佐々木亮; 前野幹; 千葉裕基; 伊藤仁弥; 中尾元基; 門坂崇秀; 立田大志郎; 西野広太郎; 甲谷次郎; 齋藤翔太; 川崎祐寛; 島野金太郎; 川上慧; 太田稔; 安斉俊久, 日本不整脈心電学会カテーテルアブレーション関連大会(Web), 2024, 2024年
• 心尖部瘤内の二つのBystanderが心外膜側のCommon Pathwayに接続することが示唆された稀有な陳旧性心筋梗塞後心室頻拍の1例
  中尾元基; 渡邉昌也; 門坂崇秀; 小泉拓也; 夏井宏征; 甲谷次郎; 西野広太郎; 立田大志朗; 天満太郎; 安斉俊久; 横式尚司; 南部忠詞; 四倉昭彦; 吉田泉; 櫻井正之, 臨床心臓電気生理, 47, 105, 114, 2024年
  臨床心臓電気生理研究会, 日本語
• 貧血 診療に役立つ最新の情報 心疾患に伴う貧血-内科医が知っておきたい診療のポイント-
  中尾元基; 永井利幸, Medical Practice, 41, 9, 1376, 1380, 2024年
  (株)文光堂, 日本語
• 除細動閾値テストの必要性を考えさせられた皮下植込み型除細動器の1例
  佐々木亮; 天満太郎; 平子竜大; 千葉裕基; 前野幹; 齋藤翔太; 立田大志郎; 甲谷次郎; 西野広太郎; 夏井宏征; 門坂崇秀; 中尾元基; 太田稔; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 16th, 2024年
• リードレスペースメーカ植込みを実施した左心補助人工心臓植込み患者において心室頻拍の遠隔管理に難渋した1例
  中尾元基; 天満太郎; 平子竜大; 千葉裕基; 前野幹; 佐々木亮; 齋藤翔太; 甲谷次郎; 西野広太郎; 立田大志郎; 夏井宏征; 門坂崇秀; 渡邉昌也; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 16th, 2024年
• 心房細動を合併する非虚血性心疾患患者における植込み型除細動器適切作動の検討
  西野広太郎; 天満太郎; 平子竜大; 千葉裕基; 前野幹; 佐々木亮; 齋藤翔太; 甲谷次郎; 立田大志郎; 夏井宏征; 門坂崇秀; 中尾元基; 渡邉昌也; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 16th, 2024年
• 植込み型左室補助装置による電磁干渉を回避しえた皮下植込み型除細動器の症例
  門坂崇秀; 天満太郎; 渡邉昌也; 平子竜大; 千葉裕基; 前野幹; 佐々木亮; 齋藤翔太; 西野広太郎; 甲谷次郎; 立田大志郎; 夏井宏征; 中尾元基; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 16th, 2024年
• 植込み型除細動器の頻拍検出設定においてエキスパートコンセンサスの盲信により適切な頻拍検出がなされなかった1例
  立田大志郎; 天満太郎; 平子竜大; 千葉裕基; 前野幹; 佐々木亮; 齋藤翔太; 甲谷次郎; 西野広太郎; 夏井宏征; 門坂崇秀; 中尾元基; 渡邉昌也; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 16th, 2024年
• 導線露出を伴うRiata ICDリードに対して,経静脈および外科的アプローチによるハイブリッド治療が有効であったデバイス感染の1例
  夏井宏征; 天満太郎; 渡邉昌也; 平子竜大; 千葉裕基; 前野幹; 佐々木亮; 齋藤翔太; 甲谷次郎; 立田大志郎; 西野広太郎; 門坂崇秀; 中尾元基; 南田大朗; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 16th, 2024年
• 高齢者における心臓突然死予防目的の植込み型心臓デバイスの有効性
  天満太郎; 齋藤翔太; 甲谷次郎; 西野広太郎; 立田大志郎; 夏井宏征; 門坂崇秀; 中尾元基; 平子竜大; 千葉裕基; 前野幹; 佐々木亮; 渡邉昌也; 渡邉昌也; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 16th, 2024年
• 日本人における2019HRS/EHRA/APHRS/LAHRS Expert Consensusに基づいた植込み型除細動器治療設定の有効性
  甲谷次郎; 天満太郎; 平子竜大; 千葉裕基; 前野幹; 佐々木亮; 齋藤翔太; 立田大志郎; 西野広太郎; 夏井宏征; 門坂崇秀; 中尾元基; 渡邉昌也; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 16th, 2024年
• 体重増加とともにlead位置が大きく変動し,不適切作動に至った皮下植込み型除細動器の1例
  齋藤翔太; 天満太郎; 西野広太郎; 甲谷次郎; 立田大志郎; 夏井宏征; 門坂崇秀; 平子竜大; 中尾元基; 千葉裕基; 前野幹; 佐々木亮; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 16th, 2024年
• 特集 めざせ! 一歩進んだ周術期管理 《術前患者評価と対応》 循環器疾患
  中尾 元基; 永井 利幸, 耳鼻咽喉科・頭頸部外科, 95, 13, 1078, 1082, 2023年12月20日
  株式会社医学書院, 日本語
• 特集 心不全に併存する貧血へのアプローチ
  中尾 元基; 永井 利幸, 日本医事新報, 5188, 18, 32, 2023年09月30日
  日本医事新報社, 日本語
• 大学病院と地域中核病院における重症心疾患を対象とした遠隔診療システム運用の有用性—特集 遠隔医療システムの到達点と可能性 ; 多様化する現場ニーズの支援ツールとしての効用
  中尾 元基; 永井 利幸, 月刊新医療, 50, 6, 68, 71, 2023年06月
  エム・イー振興協会, 日本語
• 高出力ペーシングによるQRS波形変化がヒス束伝導路の推定に有効であった前中隔副伝導路を有するWPW症候群の1例
  立田大志郎; 天満太郎; 齋藤翔太; 甲谷次郎; 西野広太郎; 夏井宏征; 門坂崇秀; 中尾元基; 小野太祐; 渡邉昌也; 安斉俊久, 日本不整脈心電学会カテーテルアブレーション関連大会(Web), 2023, 2023年
• Epicardial connectionが疑われ大動脈無冠尖から有効通電が得られたPeri-mitral atrial flutterの1例
  門坂崇秀; 天満太郎; 平子竜大; 千葉裕基; 前野幹; 佐々木亮; 斎藤翔太; 西野広太郎; 甲谷次郎; 立田大志郎; 夏井宏征; 中尾元基; 渡邉昌也; 安斉俊久, 日本不整脈心電学会カテーテルアブレーション関連大会(Web), 2023, 2023年
• 今月の特集 ｢心不全パンデミック｣を迎え撃つ! 心不全のバイオマーカー 心筋トロポニン
  中尾 元基; 永井 利幸, 臨床検査, 66, 3, 236, 242, 2022年03月15日
  株式会社医学書院, 日本語
• 高出力ショックによりショックインピーダンスの改善を認めた1例
  門坂崇秀; 渡邉昌也; 千葉裕基; 佐々木亮; 前野幹; 平子竜大; 夏井宏征; 小泉拓也; 甲谷太郎; 中尾元基; 萩原光; 鎌田塁; 天満太郎; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 14th, 2022年
• Intrinsic anti-tachycardia pacingにより植込み型除細動器のショック治療を回避することができた1例
  萩原光; 渡邉昌也; 平子竜大; 千葉裕基; 前野幹; 佐々木亮; 甲谷次郎; 立田大志郎; 西野広太郎; 夏井宏征; 門坂崇秀; 小泉拓也; 中尾元基; 甲谷太郎; 小西崇夫; 佐藤琢真; 鎌田塁; 安斉俊久, 植込みデバイス関連冬季大会プログラム・抄録集(Web), 14th, 2022年
• 難治性VTを合併した重症心不全患者に対し,LVAD装着時に心外膜側アブレーションを施行した1例
  西野広太郎; 渡邉昌也; 青柳裕之; 甲谷次郎; 立田大志郎; 夏井宏征; 門坂崇秀; 小泉拓也; 甲谷太郎; 中尾元基; 天満太郎; 安斉俊久, 日本不整脈心電学会カテーテルアブレーション関連大会(Web), 2022, 2022年
• 僧帽弁輪旋回型心房頻拍に対しEarly meets late lower threshold機能が有用であった1例
  平子竜大; 佐々木亮; 前野幹; 千葉裕基; 伊藤仁弥; 太田稔; 天満太郎; 萩原光; 甲谷太郎; 中尾元基; 小泉拓也; 門坂崇秀; 夏井宏征; 西野広太郎; 立田大志郎; 甲谷次郎; 渡邉昌也, 日本不整脈心電学会カテーテルアブレーション関連大会(Web), 2022, 2022年
• 診断と治療の手技-診察室これ1冊-第1部 診断 第1章 問診・意識・身体診察 15 心音聴取
  中尾元基; 永井利幸, 診断と治療, 109, 13, 64, 70, 2021年03月24日
  (株)診断と治療社, 日本語
• Intramural Tissueの二つの遅延伝導領域を交互に伝播することで維持されるリエントリーを機序とする交代性QRS波形を呈するVTを認めた非虚血性心筋症の1例
  鎌田塁; 渡邉昌也; 天満太郎; 萩原光; 甲谷太郎; 中尾元基; 安斉俊久; 横式尚司; 四倉昭彦; 南部忠詞; 吉田泉; 櫻井正之, 臨床心臓電気生理, 44, 2021年
• 器質的心疾患患者における繰り返す心室頻拍後の心臓死規定因子の検討
  小泉拓也; 鎌田塁; 夏井宏征; 門坂崇秀; 中尾元基; 甲谷太郎; 萩原光; 渡邉昌也; 横式尚司; 安斉俊久, 日本心臓病学会学術集会(Web), 69th, 2021年
• 心臓サルコイドーシス患者でfragmented QRSは、心事故、慢性期致死性不整脈と関連する
  萩原 光; 渡邉 昌也; 中尾 元基; 甲谷 太郎; 小林 雄太; 加藤 喜哉; 小森山 弘和; 鎌田 塁; 永井 利幸; 安斉 俊久, 日本サルコイドーシス/肉芽腫性疾患学会雑誌, 40, サプリメント号, 56, 56, 2020年10月
  日本サルコイドーシス, 日本語
• 大動脈無冠尖起源の心房頻拍の1例
  鎌田塁; 渡邉昌也; 天満太郎; 萩原光; 高橋佑美; 甲谷太郎; 中尾元基; 横式尚司; 三山博史; 高橋雅之; 佐々木亮; 千葉裕基; 平子竜大; 前野幹; 安斉俊久, 日本不整脈心電学会カテーテルアブレーション委員会公開研究会プログラム・抄録集, 2019, 2019年
• OFDIガイドPCIにおける造影剤とデキストランの運用性の検討
  伊藤 仁弥; 足達 勇; 平郡 紗季; 玉置 陽生; 中尾 元基; 松谷 健一; 正木 芳宏; 清水 紀宏; 平林 高之, 公益社団法人北海道臨床工学技士会会誌, 28, 79, 81, 2018年09月
  血管内画像の取得において、当院で初めてサヴィオゾール輸液(以下、デキストラン)使用症例を1例経験したため、当初より使用してきたオイパロミン370(以下、造影剤)と比して両者の運用性について検討した。対象は60歳代男性で、冠動脈造影検査により右冠動脈(#1 100%)、左前下行枝(#6 75%、FFR 0.63)の2枝病変との診断を受けた。冠動脈造影検査の1ヵ月後、#6に対して造影剤とデキストランを使用してOFDIガイドPCIを実施した。血管内画像取得時のフラッシュデバイスの使い分けについては、まずデキストランのみを使用し、画像の見え方次第で組成を変更していくことにした。結果、OFDIを6回使用し、ステントを留置して#6(75%→25%)で終了した。全体を通して、今回は組成にかかわらず造影剤を使用した場合に明瞭な画像が得られた。造影剤を使用したときより造影剤を使用しなかったときの方が血管内腔と血管内膜の境界線が不鮮明である傾向があった。使用回数が最も多い造影剤とデキストランのハーフ混合液に関しては、回数を重ねるにつれてdistal側(Pullback開始直後)の乱流によるアーチファクトが徐々に改善している傾向にあった。, (公社)北海道臨床工学技士会, 日本語
• 横行結腸癌に合併したトルーソー症候群と考えられた1例
  高橋 直規; 松谷 健一; 玉置 陽生; 中尾 元基; 正木 芳宏; 清水 紀宏; 平林 高之; 本間 友樹; 横田 良一, 砂川市立病院医学雑誌, 31, 1, 7, 9, 2018年07月
  症例は40歳代女性で、突然発症の左側胸部痛で受診し、造影CTで両側深部静脈血栓症・両側肺血栓塞栓症・多発肝腫瘤を認めた。肝胆道系酵素の上昇を認め、凝固機能検査では、D-Dimerの上昇を認めた。腫瘍マーカーはCEA、CA19-9、CA125の上昇を認めたが、PIVKA2は正常範囲であった。胸部単純X線写真では、心胸郭比44%、左下肺野にすりガラス影を認めた。造影CT検査では、両側肺動脈と両側大腿〜深部静脈に血栓像を認めた。肝両葉に多発腫瘤を認めた。第1病日より静脈血栓塞栓症に対してフォンダパリヌクス皮下注を5日間継続し、第6病日よりエドキサバンの内服に変更した。第8病日に造影CTを撮影し、右肺動脈に新規の血栓像を認めた。通常の抗凝固療法で増悪する静脈血栓症と判断し、下大静脈フィルターを留置した。第15病日に下部消化管内視鏡検査を施行し、横行結腸癌・転移性多発肝腫瘍と診断した。横行結腸癌と多発肝転移に対して化学療法行う方針となり、原発巣による腸閉塞と出血のコントロール目的に第20病日に人工肛門を造設した。横行結腸の周囲との癒着が高度で、原発巣の切除は不可能であった。第31病日に死亡した。, 砂川市立病院, 日本語
• Analysis of Expired Gas During the Hemodialysis in Patients With Cardiovascular Disease
  Motoki Nakao; Masashige Takahashi; Kou Motoi; Hikaru Hagiwara; Yoshikuni Obata; Hidetsugu Sakai; Shintaro Kinugawa; Koichi Okita, JOURNAL OF CARDIAC FAILURE, 22, 9, S192, S192, 2016年09月
  英語, 研究発表ペーパー・要旨（国際会議）
• 膵鉤部癌に対しEUS-FNA施行後、多臓器転移し、Trousseau症候群を来した1例
  中尾 元基; 成瀬 宏仁; 工藤 和洋; 下山 則彦, 函館医学誌, 39, 1, 34, 38, 2015年11月
  市立函館病院, 日本語

• 内科診断学 第4版
  医学書院, 2024年03月25日, 4260053159, 1104, ［分担執筆］
• 日本医事新報 No.5096
  中尾元基; 安斉俊久, 心不全の薬物治療-収縮機能障害HFrEFを中心として
  日本医事新報社, 2021年12月, ［共著］
• 飛行機・新幹線内での医療ハンドブック 「お客様の中にお医者様はいらっしゃいませんか?」と聞かれたら
  下畑, 享良, 航空機と循環器疾患（旅行者血栓症を含む）─心停止に遭遇したら
  医歯薬出版, 2021年07月20日, 4263206878, 168, 日本語, ［分担執筆］
• 重症心不全治療プラクティス
  安斉, 俊久
  南江堂, 2020年03月, 9784524227082, v, 192p, 日本語

• 心不全重症化の分子生物学機序に関する遺伝統計学的検証
  科学研究費助成事業
  2025年04月01日 - 2028年03月31日
  中尾 元基
  日本学術振興会, 若手研究, 北海道大学, 25K19377
• ポストゲノムワイド関連解析時代における多因子疾患心不全の形成および重症化の遺伝環境要因解明
  ゲノム医療実現推進プラットフォーム事業
  2025年07月 - 2028年03月
  国立研究開発法人日本医療研究開発機構（AMED）, 研究代表者, 25132839
• 臨床応用にむけた効果的な光除細動方法の開発
  科学研究費助成事業
  2022年04月01日 - 2025年03月31日
  中尾 元基
  心房筋にChR2(チャネルロドプシン2)を発現させたマウスをダブルトランスジェニック技術を用いて作成し、ChR2-tdTomatoの発現を確認した。ランゲンドル フ灌流心に対して、右心房を心外膜側から青色光(470nm)で刺激する心房光照射系を確立した。KACh-channel activatorであるCarbacholを溶解し、さらに低カリ ウム状態にした溶液(Carbachol + 低カリウム溶液)を灌流し、右心房に電気的連続刺激を行うことで心房細動を誘発した。心房細動誘発後に右心房にパルス光 刺激を行い、心房細動抑制効果を検証した。活動電位持続中に実施されるパルス光刺激によるAPD延長効果およびERP延長効果を、光学マッピング法を用いて観察 した。パルス光刺激による光除細動時の活動電位波形を、光学マッピング法を用いて観察した。Carbachol + 低カリウム溶液灌流および心房連続電気刺激により 誘発された心房細動はパルス光刺激により光除細動された。光除細動率はパルス光刺激の光強度およびパルス幅に依存した。絶対不応期を含む活動電位持続中に 実施されるパルス光刺激によりAPDは有意に延長し、ERPも同様に有意に延長した。APDおよびERPは活動電位再分極相でパルス光刺激を受けた場合に最も延長し た。また、ERP延長効果は光刺激のパルス幅に依存した。一方で一定値以上の光強度はERP延長に追加効果を与えなかった。パルス光刺激による光除細動はAPDの 延長を伴って実施された。今後、照射時相ごとの心房細動停止効果を確認する。
  日本学術振興会, 若手研究, 北海道大学, 22K16093
• 光遺伝学を用いた効果的な心房細動光除細法の開発
  循環医学分野 若手研究者助成
  2023年12月 - 2024年12月
  公益財団法人先進医薬研究振興財団, 研究代表者
• 機械学習を用いた新たな自律神経評価法による慢性心不全重症化予測モデルの開発
  アカデミックサポート助成
  2023年 - 2023年
  バイエル薬品, 研究代表者
• 光照射時相に着目した効果的な心房細動光除細動方法の開発
  若手研究人材育成事業助成
  2023年 - 2023年
  ノーステック財団, 研究代表者

• 動作解析データ取得方法及び動作解析データ取得システム
  特許権, 永井 利幸; 中尾 元基; 小川 貴弘; 平田 健司; 千代 邦弘; 大津 学, 国立大学法人北海道大学, インフォコム株式会社
  特願2021-012431, 2021年01月28日
  特開2022-115705, 2022年08月09日
  特許7694895, 2025年06月10日
  202203014082967302