Mar. 2025, The Uehara Memorial Foundation, The Uehara Memorial Foundation Resarch Grants　　　　　　　　　　　　　　　
Elucidation of the Mechanisms of Fatal Arrhythmias induced by Neuropeptide-Y

Dec. 2024, Department of Cardiology, Keio University School of Medicine, Keishinkai Award　　　　　　　　　　　　　　　

Mar. 2021, Hokkaido University Graduate School of Medicine, Award for Excellence in Research of the Hokkaido University Graduate School of Medicine　　　　　　　　　　　　　　　
Elucidation of Regulatory Mechanisms of Inflammation in Cardiovascular Remodeling

Nov. 2014, Japan Medical Association, Medical Research Encouragement Prize of The Japan Medical Association　　　　　　　　　　　　　　　

2005, 慶應義塾大学医学振興基金、特別研究奨励　　　　　　　　　　　　　　　
Japan

2004, 第３３回かなえ医薬振興財団 研究助成　　　　　　　　　　　　　　　
Japan

2003, Finalist of Poster Competition, The 76th annual session meeting of American Heart Association Annual Scientific Meeting　　　　　　　　　　　　　　　

2001, 三四会研究奨励賞　　　　　　　　　　　　　　　
Japan

2000, 慶應義塾大学医学部 坂口記念研究助成B　　　　　　　　　　　　　　　
Japan

1999, 日本心臓財団 分子循環器研究助成　　　　　　　　　　　　　　　
Japan

1999, 武田科学振興財団 研究助成　　　　　　　　　　　　　　　
Japan

1997, American Heart Association, California Affiliate, Post-doctoral Fellowship Award　　　　　　　　　　　　　　　
Japan

1996, Young Investigator Travel Award, American Heart Association Council for Basic Science Research　　　　　　　　　　　　　　　

1995, 病態代謝研究会留学助成　　　　　　　　　　　　　　　
Japan

1994, 慶応医師会研究奨励賞　　　　　　　　　　　　　　　
Japan

Editorial to "Can lead damage be ruled out using defibrillation threshold testing in patients with very high-impedance shock leads?".
Taro Temma, Toshihisa Anzai
Journal of arrhythmia, 41, 2, e70040, Apr. 2025, [Domestic magazines]
English

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, Apr. 2025, [International Magazine]
English, Scientific journal, 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.

2023 Update of the Japanese Heart Failure Society Scientific Statement on BNP and NT-proBNP levels in Heart Failure Practice.
Masatoshi Minamisawa, Toshihisa Anzai, Takayuki Inomata, Koichiro Kinugawa, Yasushi Sakata, Naoki Sato, Hiroyuki Tsutsui, Kazuhiro Yamamoto, Michihiro Yoshimura, Yoshihiko Saito, Koichiro Kuwahara
Journal of cardiac failure, 20 Mar. 2025, [International Magazine]
English, Scientific journal, This revised 2023 statement on blood brain (B-type) natriuretic peptide (BNP) and N-terminal prohormone of brain (B-type) natriuretic peptide (NT-proBNP) represents an expert consensus that aims to enhance efficient referral from general practitioners or non-cardiovascular specialists, providing a comprehensive, up-to-date perspective on BNP and NT-proBNP in the diagnosis and management of heart failure, with a focus on the following two major modifications: (1) Changes regarding cutoff values for BNP and NT-proBNP (criteria for heart failure diagnosis and referral criteria to cardiovascular specialists). (2) Content related to heart failure management using BNP and NT-proBNP (BNP-guided therapy).

Impact of snowfall on emergency medical system and mortality in patients with acute coronary syndrome.
Yuki Mori, Sakae Takenaka, Toshiyuki Nagai, Kohei Saiin, Akinori Takahashi, Yoshifumi Mizuguchi, Takao Konishi, Toshihisa Anzai, Daisuke Hotta, Mitsunori Kamigaki, Seiji Yamazaki, Tsutomu Fujita, Takehiro Yamashita, Kandoh Kawahatsu, Takashi Suzuki, Yoichi Nozaki, Taku Sakurada, Takashi Takenaka, Yasumi Igarashi, Takao Makino
Scientific reports, 15, 1, 7262, 7262, 01 Mar. 2025, [International Magazine]
English, Scientific journal, Acute coronary syndrome (ACS) requires rapid transportation by the emergency medical system (EMS). In snowy areas, traffic conditions may delay EMS transport times and increase mortality rate of ACS. However, there is a paucity of systemic data showing how snowfall affects the EMS and mortality in patients with ACS. This study aimed to investigate the impact of snowfall on the EMS transport times and in-hospital death in patients with ACS. We examined 2387 consecutive ACS patients who were transported via EMS to hospitals participating in the Sapporo City ACS network between April 2013 and April 2023. The patients were divided into two groups based on their arrival on either a snowy day (n = 612, 26%) or a non-snowy day (n = 1775, 74%), as determined by historical weather records from the Japan Meteorological Agency for the Sapporo area. The median age was 68 years, 1754 (74.6%) patients were male. Patients in the snowy day group had longer median time from an EMS call to hospital than those in the non-snowy day group (33 min [IQR 26-40] vs. 29 min [IQR 24-36], P < 0.001). Quantity of snowfall was associated with a delayed time from EMS call to hospital. The proportion of in-hospital death was higher in the snowy day group compared to the non-snowy day group (7.3% vs. 4.6%, P = 0.011). Multivariable logistic regression analysis showed that the snowfall was independently associated with higher incidence of in-hospital death (odds ratio 1.57, 95% confidence interval 1.00-2.47, P = 0.048). In conclusion, snowfall had a significant impact on the EMS and mortality in patients with ACS in an urban city in Japan.

Prevalence, incidence, and clinical features of cardiac involvement in patients with pulmonary sarcoidosis.
Junichi Nakamura, Takahiro Sato, Hiroshi Ohira, Shuhei Yoshikawa, Takeshi Hattori, Osamu Manabe, Noriko Oyama-Manabe, Satonori Tsuneta, Hirokazu Kimura, Sakae Takenaka, Toshiyuki Nagai, Toshihisa Anzai, Masaharu Nishimura, Isao Yokota, Ichizo Tsujino, Satoshi Konnno
Respiratory medicine, 238, 107954, 107954, Mar. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: The epidemiology and characteristics of cardiac involvement in patients with pulmonary sarcoidosis remain unclear. We aimed to determine the prevalence, incidence, and clinical features of cardiac sarcoidosis in patients with pulmonary sarcoidosis. METHODS: The characteristics of patients with biopsy-proven pulmonary sarcoidosis were retrospectively evaluated. Cardiac sarcoidosis was diagnosed via evaluations, including 18F-fluorodeoxyglucose positron emission tomography at the time of diagnosis of pulmonary sarcoidosis and during follow-up. Characteristics of patients with and without cardiac complications were compared. RESULTS: In total, 438 patients with pulmonary sarcoidosis were included, of which 40 (9.1 %) were diagnosed with cardiac sarcoidosis at the time of diagnosis of pulmonary sarcoidosis. During the follow-up period, 14 patients (4 %) developed cardiac complications (0.0075/person-years). Electrocardiographic abnormalities were the most common findings leading to the diagnosis of cardiac sarcoidosis (85 %). Compared to patients without cardiac involvement, those with cardiac sarcoidosis had lower serum angiotensin converting enzyme concentration [19.9 (15.5-25.1) vs. 17.4 (12.6-23.8) U/L)], higher rates of kidney complications (3 vs. 13 %), fewer ocular complications (78 vs. 17 %), and lower lymphocyte levels [35.8 (18.6-53) vs. 25.1 (14.2-38.2)%] and CD4/CD8 ratios [4.8 (3.1-7.5)% vs. 3.9 (1.8-6)%] in bronchoalveolar lavage fluid analysis. CONCLUSION: At the time of diagnosis of pulmonary sarcoidosis, cardiac complications occurred in approximately 10 % of the patients and developed in 0.0075/person-year during follow-up. Low serum angiotensin converting enzyme concentration, lymphocyte level and CD4/CD8 ratio in the bronchoalveolar lavage fluid may be unique features of patients with cardiac sarcoidosis.

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, 07 Feb. 2025, [International Magazine]
English, Scientific journal, 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.

Inappropriate Shocks in Brugada Syndrome Patients With a Subcutaneous Implantable Cardioverter Defibrillator.
Masaya Watanabe, Tadafumi Nanbu, Yuki Ishidoya, George Suzuki, Akihiko Yotsukura, Izumi Yoshida, Yoshitaka Tanaka, Kazushige Inoue, Junko Mitsuishi, Tomomi Kanno, Masayuki Sakurai, Toshihisa Anzai
Pacing and clinical electrophysiology : PACE, 27 Jan. 2025, [International Magazine]
English, Scientific journal, BACKGROUND: This study aimed to compare inappropriate shock (IAS) rates between subcutaneous implantable cardioverter-defibrillator (S-ICD) and transvenous ICD (TV-ICD) in Brugada syndrome (BrS) patients and identify risk factors for IAS in S-ICD use. METHODS: We enrolled consecutive patients with BrS who underwent ICD implantation between 2013 and 2023. Data on clinical characteristics, S-ICD screening test data, and IAS occurrence were retrospectively analyzed. RESULTS: In total, 74 patients (40 with S-ICDs and 34 with TV-ICD) were enrolled in the study. During a median follow-up of 4.6 years, IAS occurred in nine S-ICD and three TV-ICD patients, exhibiting a non-statistically significant trend (log-rank p = 0.103) toward a higher incidence in the S-ICD group. The incidence of IAS related to non-atrial tachyarrhythmia (non-AT) causes was significantly higher in the S-ICD group than in the TV-ICD group (log-rank p = 0.014). Fewer electrocardiography (ECG) sensing vectors passing the screening test at both the baseline and exercise test (hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.09-0.85; p = 0.21) and detection of ATs (HR 5.25, 95% CI 1.15-24.05; p = -0.048) were associated with IAS in patients with S-ICD. CONCLUSION: No significant difference was observed in the overall incidence of IAS between the S-ICD and TV-ICD groups; however, IAS due to non-AT causes occurred more frequently in the S-ICD group. Fewer ECG sensing vectors passing screening were significantly correlated with the IAS when exercise test results were considered. Therefore, ECG screening, including exercise testing, is preferable for S-ICD candidates.

Clinical Utility of Near-Infrared Spectroscopy Intravascular Ultrasound in the Assessment of Rapidly Progressive Cardiac Allograft Vasculopathy.
Sakae Takenaka, Takuma Sato, Toshiyuki Nagai, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 89, 2, 255, 255, 24 Jan. 2025, [Domestic magazines]
English, Scientific journal

Optimal Cut Plane for Tricuspid Annular Plane Systolic Excursion Measurement.
Michito Murayama, Sanae Kaga, Hisao Nishino, Yusuke Yanagi, Mana Goto, Fuka Ando, Shinobu Yokoyama, Marina Yamaguchi, Kazunori Okada, Masahiro Nakabachi, Makoto Kambayashi, Yui Shimono, Kosuke Nakamura, Yoji Tamaki, Suguru Ishizaka, Hiroyuki Iwano, Toshiyuki Nagai, Toshihisa Anzai
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, 14 Jan. 2025, [International Magazine]
English, Scientific journal

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, Jan. 2025, [Domestic magazines]
English, Scientific journal, 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.

Role of anatomical regurgitant orifice area of the tricuspid valve measurements in patients with beyond severe tricuspid regurgitation.
Michito Murayama, Suguru Ishizaka, Keita Sakaguchi, Rion Ando, Hisao Nishino, Sanae Kaga, Toshihisa Anzai
Journal of echocardiography, 24 Dec. 2024, [Domestic magazines]
English, Scientific journal

Effect of Low-dose Administration of Carperitide for Acute Heart Failure: the LASCAR-AHF trial
Satoshi Honda, Toshiyuki Nagai, Yasuyuki Honda, Hiroki Nakano, Takanori Kawabata, Hirotada Maeda, Koko Asakura, Naotsugu Iwakami, Sakae Takenaka, Yoshiya Kato, Yusuke Tokuda, Takafumi Yamane, Yutaka Furukawa, Takeshi Kitai, Yasuhide Asaumi, Shuzo Nishihara, Atsushi Mizuno, Tetsuo Yamaguchi, Teruo Noguchi, Satoshi Yasuda, Toshihisa Anzai
European Heart Journal: Acute Cardiovascular Care, Oxford University Press (OUP), 04 Dec. 2024
Scientific journal, Abstract

Background

The effects of low-dose carperitide on long-term clinical outcomes of patients with acute heart failure (AHF) have not yet been fully elucidated. This study aimed to evaluate the effects of low-dose intravenous carperitide on the long-term clinical outcomes of patients with AHF.

Methods

In this multicentre, open-label, randomised controlled trial, 247 patients with AHF received low-dose carperitide intravenously with standard treatment or a matching standard treatment for 72 h from November 2014 to March 2021 across nine sites in Japan. The primary endpoint was a composite of all-cause death and heart failure hospitalisation within 2 years.

Results

The primary endpoint was observed in 36 of 122 patients (29.5%) and 35 of 125 patients (28.0%) in the carperitide group and standard treatment groups, respectively (hazard ratio 1.26; 95% confidence interval (CI) 0.78–2.06, P = 0.827). No significant differences were observed in the secondary endpoints, including cumulative urine volume at 72 h; change in the degree of dyspnoea over 72 h; and changes in brain natriuretic peptide, cystatin C, renin, aldosterone, and catecholamine levels at 72 h post randomisation between the groups. A greater decrease in the estimated glomerular filtration rate was observed in the carperitide group compared with the standard treatment group (inter-group difference -3.9 ml/min/1.73 m2; 95% CI -7.0 to -0.8).

Conclusion

In patients with AHF, low-dose carperitide did not reduce long-term mortality or hospitalisation events when combined with standard treatment. Because patient enrolment was terminated prematurely, the study was underpowered and inconclusive.

Clinical and Histopathological Characteristics of Patients With Myocarditis After mRNA COVID-19 Vaccination
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, Japanese Circulation Society, 01 Nov. 2024
Scientific journal

Validation of Left Ventricular Filling Pressure Evaluation by Order of Tricuspid and Mitral Valve Opening in Patients With Atrial Fibrillation.
Hisao Nishino, Michito Murayama, Hiroyuki Iwano, Nobuyuki Kagiyama, Yutaka Nakamura, Yuka Akama, Misako Toki, Sachiko Takamatsu, Taiji Okada, Yasuyuki Chiba, Masahiro Nakabachi, Shinobu Yokoyama, Mana Goto, Yukino Suzuki, Suguru Ishizaka, Ko Motoi, Yoji Tamaki, Hiroyuki Aoyagi, Kosuke Nakamura, Sanae Kaga, Chiaki Watanabe, Kiwamu Kamiya, Toshiyuki Nagai, Takanori Teshima, Toshihisa Anzai
Circulation. Cardiovascular imaging, 17, 11, e017134, Nov. 2024, [International Magazine]
English, Scientific journal, BACKGROUND: Accurate assessment of left ventricular filling pressure in patients with atrial fibrillation or flutter (AF) remains difficult. A novel 2-dimensional scoring system, visually assessing time difference between mitral valve and tricuspid valve opening (VMT) score, based on temporal analysis of early diastolic valve opening, could be applied to these patients. We aimed to determine the usefulness of the VMT score in patients with AF. METHODS: We analyzed 119 consecutive patients with AF who underwent cardiac catheterization as a derivation cohort. The diagnostic performance of the VMT score was further evaluated in an external data set containing 189 patients with AF. Elevated left ventricular filling pressure was defined as a mean pulmonary arterial wedge pressure ≥15 mm Hg. The time sequence of atrioventricular valve opening was visually assessed and scored (0, tricuspid valve first; 1, simultaneous; 2, mitral valve first). When the inferior vena cava was dilated, 1 point was added, and the VMT score was finally graded as 0 to 3. Conventional Doppler parameters to estimate left ventricular filling pressure were also measured. RESULTS: Pulmonary arterial wedge pressure was elevated with an increase in the VMT score (0: 10±3, 1: 13±5, 2: 22±7, 3: 27±6 mm Hg; P<0.001), resulting in a significant rise in pulmonary arterial wedge pressure from VMT score 1 to 2. VMT≥2 predicted elevated pulmonary arterial wedge pressure with an accuracy of 87%, and the diagnostic accuracy of the VMT score was significantly higher than that of conventional Doppler parameters (C index, 0.88 versus 0.54-0.68; P<0.001). In addition, VMT ≥2 showed an incremental predictive value over plasma brain natriuretic peptide levels (C index, 0.79-0.93; P<0.001). In the external validation cohort, VMT≥2 demonstrated acceptable accuracy of 72%. CONCLUSIONS: VMT scoring was a useful echocardiographic marker of elevated left ventricular filling pressure and had an incremental benefit over practical biomarkers in patients with AF.

From Optional to Default - Enhancing Article Viewership Through X (Formerly Twitter) Posting.
Atsushi Mizuno, Daisuke Yoneoka, Takuya Kishi, Kenya Kusunose, Chisa Matsumoto, Yuki Sahashi, Mari Ishida, Shoji Sanada, Memori Fukuda, Tadafumi Sugimoto, Miki Hirano, Masataka Sata, Toshihisa Anzai, Koichi Node
Circulation reports, 6, 9, 389, 394, 10 Sep. 2024, [Domestic magazines]
English, Scientific journal, BACKGROUND: The influence of a change to a default X summary posting strategy on article viewership has not been investigated. METHODS AND RESULTS: We conducted a retrospective analysis of X-posting rates and journal viewership data for both the Circulation Journal and Circulation Reports from April 2022 to September 2023. Following protocol modifications in March 2023, there was a notable increase in the X-posting rate from 12.4% to 61.7%, along with an uptick in median access counts to article pages within 30 days, from 175 to 231.5. CONCLUSIONS: Trend analysis of journal viewership after a default X-posting strategy revealed an increase in viewer access.

Orthotopic heart transplantation in patient with situs inversus and pectus excavatum: a case report.
Satoru Wakasa, Tomonori Ooka, Takuma Sato, Yasushige Shingu, Nobuyasu Kato, Toshiyuki Nagai, Toshihisa Anzai, Minoru Ono, Yoshiro Matsui
Surgical case reports, 10, 1, 202, 202, 30 Aug. 2024, [International Magazine]
English, Scientific journal, BACKGROUND: Heart transplantation in patients with situs inversus is challenging, especially in terms of reconstruction of the systemic venous return. Several rerouting techniques have been presented but are associated with vulnerability to external compression, which might cause hemodynamic instability, especially in the presence of chest deformity. In this study, we report a rare case of successful heart transplantation in the presence of situs inversus and pectus excavatum. CASE PRESENTATION: A 55-year-old man, with a history of surgeries for corrected transposition of the great arteries with ventricular septal defect, was registered for heart transplantation owing to progression of heart failure. Subsequently, he had undergone a left ventricular assist device implantation; 14 years after registration, he underwent transplantation of the heart with normal anatomy. The inferior vena cava was reconstructed by anastomosing the left atria with a counterclockwise rotation of the donor heart and by lengthening the recipient inferior vena cava with a conduit made of the residual right atrial tissue. The superior vena cava was reconstructed using a donor innominate vein harvested with sufficient length. After successful weaning from cardiopulmonary bypass, the chest could not be closed because the heart was compressed owing to chest deformity, resulting in hemodynamic instability. Therefore, to exclude the left lung, a left pericardial screen was created using a bovine pericardium, allowing the chest to be closed with acceptable hemodynamics. The patient suffered postoperatively from a higher venous pressure, suggesting an obstruction of venous return early after surgery. The obstruction gradually resolved, and the patient was transferred for rehabilitation. CONCLUSIONS: Heart transplantation in the presence of situs inversus is challenging; moreover, the presence of pectus excavatum further complicates the procedure. The paradoxically larger left lung and chest deformity compressed and impaired reconstructed systemic venous return. Although intrathoracic exclusion of the left lung was effective, an intraoperative or early postoperative thoracoplasty for pectus excavatum was also a viable option. Patient-specific management is mandatory, depending on the anatomy.

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, 21 Aug. 2024, [International Magazine]
English, Scientific journal, 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, 132452, 132452, 14 Aug. 2024, [International Magazine]
English, Scientific journal, 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.

Bereaved family members' perspectives on quality of death in deceased acute cardiovascular disease patients compared with cancer patients - a comparison of the J-HOPE3 study and the quality of palliative care in heart disease (Q-PACH) study.
Takahiro Suzuki, Mitsunori Miyashita, Takashi Kohno, Jeffrey Rewley, Naoko Igarashi, Maho Aoyama, Michiaki Higashitani, Naoto Kawamatsu, Takeshi Kitai, Tatsuhiro Shibata, Makoto Takei, Kotaro Nochioka, Gaku Nakazawa, Hiroki Shiomi, Shigeru Tateno, Toshihisa Anzai, Atsushi Mizuno
BMC palliative care, 23, 1, 188, 188, 26 Jul. 2024, [International Magazine]
English, Scientific journal, BACKGROUND: Outcome measures during acute cardiovascular disease (CVD) phases, such as quality of death, have not been thoroughly evaluated. This is the first study that compared the family members' perceptions of quality of death in deceased CVD patients and in deceased cancer patients using a bereaved family survey. METHODS: Retrospectively sent questionnaire to consecutive family members of deceased patients with CVD from ten tertiary hospitals from October 2017 to August 2018. We used the short version of the Good Death Inventory (GDI) and assessed overall care satisfaction. Referencing the GDI, the quality of death was compared between CVD patients admitted to a non-palliative care unit (non-PCU) and cancer patients in palliative care units (PCU) and non-PCUs in the Japan Hospice and Palliative Care Evaluation Study (J-HOPE Study). Additionally, in the adjusted analysis, multivariable linear regression was performed for total GDI score adjusted by the patient and participant characteristics to estimate the difference between CVD and other patients. RESULTS: Of the 243 bereaved family responses in agreement (response rate: 58.7%) for CVD patients, deceased patients comprised 133 (54.7%) men who were 80.2 ± 12.2 years old on admission. The GDI score among CVD patients (75.0 ± 15.7) was lower (worse) than that of cancer patients in the PCUs (80.2 ± 14.3), but higher than in non-PCUs (74.4 ± 15.2). After adjustment, the total GDI score for CVD patients was 7.10 points lower [95% CI: 5.22-8.97] than for cancer patients in PCUs and showed no significant differences compared with those in non-PCUs (estimates, 1.62; 95% CI [-0.46 to 5.22]). CONCLUSIONS: The quality of death perceived by bereaved family members among deceased acute CVD patients did not differ significantly from that of deceased cancer patients in general wards, however, was significantly lower than that of deceased cancer patients admitted in PCUs.

Phenotypic Characteristics of Acute Decompensated Heart Failure With Preserved Ejection Fraction in Japanese Population.
Yohei Sotomi, Toshiyuki Nagai, Shungo Hikoso, Tsutomu Yoshikawa, Yoshihiko Saito, Kazuhiro Yamamoto, Yoshio Yasumura, Takahisa Yamada, Toshihisa Anzai, Yasushi Sakata
JACC. Asia, 4, 7, 566, 568, Jul. 2024, [International Magazine]
English, Scientific journal

Public awareness of palliative care for heart failure in Japan: A cross-sectional study.
Tatsuhiro Shibata, Atsushi Mizuno, Takashi Ohmori, Shogo Oishi, Kimitaka Nishizaki, Takeru Nabeta, Takuya Kishi, Toshiyuki Nagai, Toshihisa Anzai
Journal of cardiology, 03 Jun. 2024, [International Magazine]
English, BACKGROUND: Palliative care (PC) benefits cancer patients and those with heart failure (HF), improving quality of life and symptom burden. Despite guidelines recommending the integration of PC into HF care, its use remains inadequate, partly due to insufficient public awareness. This study aimed to assess the public awareness of PC for HF in Japan and identify factors associated with awareness. METHODS: A cross-sectional online survey was conducted from March 6-13, 2023, using a panel operated by Intage Inc. (Tokyo, Japan), which has a pool of 3.78 million potential Japanese respondents. The survey included 51,790 participants, matched for sex, age, and region of residence. Participants were asked about their awareness of PC eligibility for HF, along with demographic information, history of hospitalization for sudden illness, outpatient visits, and health status in the previous 2 years. The χ2 test and Cramer's V were used to analyze associations between awareness and variables, and multivariate logistic regression was used to estimate awareness predictors. RESULTS: In total, 91 % of participants were unaware of PC eligibility for HF. Age group, healthcare professional occupation, and history of hospitalization for acute myocardial infarction, acute HF, acute pulmonary embolism, and ruptured aortic aneurysm had weak to moderate associations with awareness. Multivariate analysis revealed that a history of hospitalization for sudden cardiovascular illness and being a healthcare professional were positively related to awareness, while age, female sex, and being married were associated with lower odds of awareness. CONCLUSION: The low public awareness of PC for HF in Japan underscores the importance of increasing awareness of the eligibility of PC for HF, as well as cancer, to integrate PC into HF practice as basic care.

Head-to-Head Comparison of Hepatic Vein and Superior Vena Cava Flow Velocity Waveform Analyses for Predicting Elevated Right Atrial Pressure.
Michito Murayama, Sanae Kaga, Airi Onoda, Hisao Nishino, Shinobu Yokoyama, Mana Goto, Yukino Suzuki, Yusuke Yanagi, Yui Shimono, Kosuke Nakamura, Hiroyuki Aoyagi, Yoji Tamaki, Suguru Ishizaka, Hiroyuki Iwano, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Ultrasound in medicine & biology, 03 Jun. 2024, [International Magazine]
English, Scientific journal, OBJECTIVE: Blood flow in the hepatic veins and superior vena cava (SVC) reflects right heart filling; however, their Doppler profiles are often not identical, and no studies have compared their diagnostic efficacies. We aimed to determine which venous Doppler profile is reliable for detecting elevated right atrial pressure (RAP). METHODS: In 193 patients with cardiovascular diseases who underwent cardiac catheterization within 2 d of echocardiography, the hepatic vein systolic filling fraction (HV-SFF) and the ratio of the peak systolic to diastolic forward velocities of the SVC (SVC-S/D) were measured. HV-SFF < 55% and SVC-S/D < 1.9 were regarded as elevated RAP. We also calculated the fibrosis 4 index (FIB-4) as a serum liver fibrosis marker. RESULTS: HV-SFF and SVC-S/D were feasible in 177 (92%) and 173 (90%) patients, respectively. In the 161 patients in whom both venous Doppler waveforms could be measured, HV-SFF and SVC-S/D were inversely correlated with RAP (r = -0.350, p < 0.001; r = -0.430, p < 0.001, respectively). SVC-S/D > 1.9 showed a significantly higher diagnostic accuracy of RAP elevation compared with HV-SFF < 55% (area under the curve, 0.842 vs. 0.614, p < 0.001). Multivariate analyses showed that both FIB-4 (β = -0.211, p = 0.013) and mean RAP (β = -0.319, p < 0.001) were independent determinants of HV-SFF. In contrast, not FIB-4 but mean RAP (β = -0.471, p < 0.001) was an independent determinant of SVC-S/D. The diagnostic accuracy remained unchanged when HV-SFF < 55% was considered in conjunction with the estimated RAP based on the inferior vena cava morphology. Conversely, SVC-S/D showed an incremental diagnostic value over the estimated RAP. CONCLUSIONS: SVC-S/D enabled a more accurate diagnosis of RAP elevation than HV-SFF.

Multimodal Assessment of Immunosuppressive Therapy in a Patient With Chronic Active Myocarditis 3 Months Following COVID-19 Infection.
Yuta Kobayashi, Takeshi Hamaya, Toshiyuki Nagai, Yuki Mori, Takuma Sato, Satonori Tsuneta, Kento Wakabayashi, Kohsuke Kudo, Yoshihiro Matsuno, Toshihisa Anzai
CJC open, 6, 6, 826, 829, Jun. 2024, [International Magazine]
English, Scientific journal

肺動脈弁逆流速度計測に基づく右室一回仕事係数の非侵襲的推定法　　　　　　　　　　　　　　　
立石 優太, 村山 迪史, 加賀 早苗, 塚本 真帆, 後藤 真奈, 鈴木 ゆき乃, 柳 裕介, 横山 しのぶ, 西野 久雄, 石坂 傑, 岩野 弘幸, 安斉 俊久
超音波検査技術, 49, 3, 271, 271, (一社)日本超音波検査学会, Jun. 2024
Japanese

Simultaneous epicardial ablation based on intraoperative electroanatomic mapping during left ventricular assist device implantation.
Kotaro Nishino, Masaya Watanabe, Tomonori Ooka, Takuma Sato, Toshihisa Anzai
Journal of arrhythmia, 40, 3, 632, 635, Jun. 2024, [Domestic magazines]
English, Scientific journal, Intraoperative ventricular tachycardia (VT) ablation targeting the epicardial substrate using three-dimensional electroanatomic mapping (EAM) was performed during left ventricular assist device (LVAD) implantation. We proved that EAM can be safely performed during LVAD implantation and that an ablation strategy based on electrophysiological information may reduce VT recurrence after LVAD implantation.

Validity and reliability of the palliative care needs assessment tool in Japanese patients with heart failure
Daishiro Tatsuta, Takuma Sato, Toshiyuki Nagai, Jiro Koya, Kotaro Nishino, Seiichiro Naito, Yoshifumi Mizuguchi, Taro Temma, Kiwamu Kamiya, Hisashi Narita, Kenkichi Tsuruga, Toshihisa Anzai
ESC Heart Failure, Wiley, 29 May 2024, [International Magazine]
English, Scientific journal, Abstract

Aims

Although patients with heart failure (HF) frequently experience considerable symptom burden and require significant care, most HF patients do not receive timely intervention due to the absence of a standardized method for identifying those in need of palliative care. The Needs Assessment Tool: Progressive Disease‐Heart Failure (NAT: PD‐HF) assesses the palliative care needs of patients with HF. However, its validity and reliability have yet to be fully examined. We aimed to assess the validity and reliability of the NAT: PD‐HF in Japanese patients with HF.

Methods

We prospectively enrolled 106 consecutive patients with chronic HF admitted to our university hospital between February 2023 and July 2023. Their caregivers (n = 95) and healthcare providers (n = 17) were also included. The NAT: PD‐HF was translated from English to Japanese using a forward–backward translation procedure and adapted based on Japanese cultural and medical backgrounds by our professional multidisciplinary team. We assessed the internal consistency of the Japanese NAT: PD‐HF version with Cronbach's alpha coefficient and the inter‐rater and test–retest reliabilities with Cohen's kappa coefficient. After using the tool, all participants were asked to complete a questionnaire about the tool to determine its validity.

Results

The proportion of female patients in this study was 47 (44%). The median age was 72 years [interquartile range (IQR) 59–81]. The median time spent assessing the patients' and their caregivers' needs using the Japanese NAT: PD‐HF was 14 min (IQR 12–17). The Cronbach's alpha coefficient was 0.82, and the minimum kappa coefficient was 0.77 for inter‐rater reliability and 0.88 for test–retest reliability. In total, 103 patients (97%) and all caregivers responded that the tool was easy to understand. One hundred (94%) patients and 89 (94%) caregivers felt that the tool would improve the quality of care, and 102 (96%) patients and 91 (96%) caregivers indicated that the discussions using this tool allowed them to confide in all their burdens and care needs. All healthcare providers expressed that this tool is helpful in understanding the burden and care needs of both patients and caregivers comprehensively.

Conclusions

The NAT: PD‐HF is a reliable and valid tool for Japanese patients with HF and their caregivers. This tool was very well accepted by patients, caregivers and healthcare providers to identify burdens and care needs.

Chronic Active Myocarditis After Transapical Transcatheter Aortic Valve Implantation.
Yuta Kobayashi, Toshiyuki Nagai, Kiwamu Kamiya, Satonori Tsuneta, Yasushige Shingu, Kento Wakabayashi, Kohsuke Kudo, Yoshihiro Matsuno, Satoru Wakasa, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 88, 6, 1008, 1008, 24 May 2024, [Domestic magazines]
English, Scientific journal

Is growth differentiation factor-15 a useful biomarker for chronic heart failure across body size?
Atsushi Tada, Toshiyuki Nagai, Toshihisa Anzai
International journal of cardiology, 410, 132204, 132204, 23 May 2024, [International Magazine]
English

Announcement of the 2024 JCS Meeting Activities (2).
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 88, 5, 621, 625, 25 Apr. 2024, [Domestic magazines]
English, Scientific journal

Acute onset of constrictive pericarditis due to acute myelomonocytic leukemia: A case and literature review.
Naoki Kosaka, Takanori Uchiyama, Masahiro Onozawa, Jun Nagai, Jiro Koya, Suguru Ishizaka, Toshiyuki Nagai, Yohei Ikebe, Kenjiro Kato, Zen-Ichi Tanei, Jun Sakakibara-Konishi, Yuta Hasegawa, Hiroyuki Ohigashi, Hideki Goto, Daigo Hashimoto, Hideki Ujiie, Satoshi Hirano, Satoshi Konno, Toshihisa Anzai, Koji Taniguchi, Shinya Tanaka, Takanori Teshima
Internal medicine (Tokyo, Japan), 16 Apr. 2024, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, We herein present a fatal case of constrictive pericarditis (CP) due to acute myelomonocytic leukemia (AMML) in a patient who initially complained of an acute onset of chest pain two days after COVID-19 vaccination. An autopsy revealed pericardial infiltration of leukemic cells. CP is rarely associated with leukemia and only 14 cases have been reported in the literature. The etiology of CP in previous reports included leukemic infiltration, graft-versus-host disease, drug-induced, post-radiation, autoimmune, and otherwise unidentified. This case indicates that leukemic infiltration can cause CP and that clinicians should include leukemia in the differential diagnosis of CP.

Non-invasive assessment of left ventricular filling pressure in aortic stenosis.
Hiroyuki Aoyagi, Hiroyuki Iwano, Yoji Tamaki, Michito Murayama, Suguru Ishizaka, Ko Motoi, Kosuke Nakamura, Mana Goto, Yukino Suzuki, Shinobu Yokoyama, Hisao Nishino, Sanae Kaga, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Echocardiography (Mount Kisco, N.Y.), 41, 4, e15808, Apr. 2024, [International Magazine]
English, Scientific journal, BACKGROUND: The assessment of left ventricular (LV) filling pressure (FP) is important for the management of aortic stenosis (AS) patients. Although, it is often restricted for predict LV FP in AS because of mitral annular calcification and a certain left ventricular hypertrophy. Thus, we tested the predictive ability of the algorithm for elevated LV FP in AS patients and also applied a recently-proposed echocardiographic scoring system of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score. METHODS: We enrolled consecutive 116 patients with at least moderate AS in sinus rhythm who underwent right heart catheterization and echocardiography within 7 days. Mean pulmonary artery wedge pressure (PAWP) was measured as invasive parameter of LV FP. LV diastolic dysfunction (DD) was graded according to the ASE/EACVI guidelines. The VMT score was defined as follows: time sequence of opening of mitral and tricuspid valves was scored to 0-2 (0: tricuspid valve first, 1: simultaneous, 2: mitral valve first). When the inferior vena cava was dilated, one point was added and VMT score was finally calculated as 0-3. RESULTS: Of the 116 patients, 29 patients showed elevated PAWP. Ninety patients (93%) and 67 patients (63%) showed increased values for left atrium volume index (LAVI) and E/e', respectively when the cut-off values recommended by the guidelines were applied and thus the algorism predicted elevated PAWP with a low specificity and positive predictive value (PPV). VMT ≥ 2 predicted elevated PAWP with a sensitivity of 59%, specificity of 90%, PPV of 59%, and negative predictive value of 89%. An alternative algorithm that applied tricuspid regurgitation velocity and VMT scores was tested, and its predictive ability was markedly improved. CONCLUSION: VMT score was applicable for AS patients. Alternative use of VMT score improved diagnostic accuracy of guideline-recommended algorism.

Iron supplementation is a residual piece of management in Asian patients with heart failure?
Motoki Nakao, Toshiyuki Nagai, Toshihisa Anzai
International Journal of Cardiology, 406, 132014, 132014, Elsevier BV, Apr. 2024, [International Magazine]
English, Scientific journal

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, 28 Mar. 2024, [International Magazine]
English, Scientific journal, 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.

Rapid Publication and Announcement of the 2024 JCS Meeting Activities.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 88, 4, 437, 438, 25 Mar. 2024, [Domestic magazines]
English, Scientific journal

Prolonged delirium during hospitalization is associated with worse long-term and short-term outcomes in patients with acute heart failure.
Yukio Aikawa, Soshiro Ogata, Satoshi Honda, Toshiyuki Nagai, Shunsuke Murata, Isao Morii, Toshihisa Anzai, Kunihiro Nishimura, Teruo Noguchi
International journal of cardiology, 399, 131776, 131776, 15 Mar. 2024, [International Magazine]
English, Scientific journal, BACKGROUND: The association between prolonged delirium during hospitalization and long-term prognosis in patients with acute heart failure (AHF) admitted to the cardiac intensive care unit (CICU) has not been fully elucidated. METHODS: We conducted a prospective registry study of patients with AHF admitted to the CICU at 2 hospitals from 2013 to 2021. We divided study patients into 3 groups according to the presence or absence of delirium and prolonged delirium as follows: no delirium, resolved delirium, or prolonged delirium. Main outcomes were in-hospital mortality and 3-year mortality after discharge. RESULTS: A total of 1555 patients with AHF (median age, 80 years) were included in the analysis. Of these, 406 patients (26.1%) developed delirium. We divided patients with delirium into 2 groups: the resolved delirium group (n = 201) or the prolonged delirium group (n = 205). Multivariate Cox proportional hazards models for long-term prognosis demonstrated that the prolonged delirium group had a higher incidence of all-cause death (hazard ratio [HR], 1.52; 95% CI, 1.08 to 2.14) and non-cardiovascular death (HR, 1.84; 95% CI, 1.21 to 2.78) than the resolved delirium group. Regarding in-hospital outcomes, multivariate logistic regression modeling showed that prolonged delirium is associated with all-cause death (odds ratio [OR], 9.55; 95% confidential interval [CI], 2.99 to 30.53) and cardiovascular death (OR, 13.02; 95% CI, 2.86 to 59.27) compared with resolved delirium. CONCLUSIONS: Prolonged delirium is associated with worse long-term and short-term outcomes than resolved delirium in patients with AHF.

Prognostic Value of Combined Assessments of Late Gadolinium Enhancement and Fluorodeoxyglucose Uptake in Cardiac Sarcoidosis.
Sho Kazui, Sakae Takenaka, Toshiyuki Nagai, Satonori Tsuneta, Kenji Hirata, Yoshiya Kato, Hirokazu Komoriyama, Yuta Kobayashi, Akinori Takahashi, Kiwamu Kamiya, Taro Temma, Takuma Sato, Atsushi Tada, Yutaro Yasui, Michikazu Nakai, Takahiro Sato, Ichizo Tsujino, Kohsuke Kudo, Satoshi Konno, Toshihisa Anzai
JACC. Cardiovascular imaging, 17, 6, 710, 712, 11 Mar. 2024, [International Magazine]
English

Two-Year Clinical Outcome of MitraClip Transcatheter Edge-to-Edge Repair From the J-MITRA Registry Data.
Teruhiko Imamura, Michikazu Nakai, Yoshitaka Iwanaga, Yoko Sumita, Misato Tao, Yohei Ohno, Kentaro Hayashida, Yoshihiro Morino, Yoshihiro Seo, Yoshikatsu Saiki, Toshihisa Anzai, Koichi Toda, Goro Matsumiya, Kazuhiro Yamamoto, Kenichi Hirata, Koichiro Kinugawa
Circulation journal : official journal of the Japanese Circulation Society, 88, 4, 539, 548, 06 Mar. 2024, [Domestic magazines]
English, Scientific journal, BACKGROUND: The introduction of transcatheter edge-to-edge repair for moderate-to-severe or severe mitral regurgitation (MR) utilizing the MitraClip system became reimbursed and clinically accessible in Japan in April 2018. This study presents the 2-year clinical outcomes of all consecutively treated patients who underwent MitraClip implantation in Japan and were prospectively enrolled in the Japanese Circulation Society-oriented J-MITRA registry.Methods and Results: Analysis encompassed 2,739 consecutive patients enrolled in the J-MITRA registry with informed consent (mean age: 78.3±9.6 years, 1,550 males, STS risk score 11.7±8.9), comprising 1,999 cases of functional MR, 644 of degenerative MR and 96 in a mixed group (DMR and FMR). The acute procedure success rate was 88.9%. After MitraClip implantation, >80% exhibited an MR grade ≤2+ and the trend was sustained over the 2 years. Within this observation period, the mortality rate was 19.3% and the rate of heart failure readmissions was 20.6%. The primary composite endpoint, inclusive of cardiovascular death and heart failure readmission, was significantly higher in patients with functional MR than in with degenerative MR (32.0% vs. 17.5%, P<0.001). CONCLUSIONS: The 2-year clinical outcomes after MitraClip implantation were deduced from comprehensive data within an all-Japan registry.

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, Mar. 2024
English

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, 5, 2, 152, 162, Oxford University Press (OUP), 20 Dec. 2023, [International Magazine]
English, Scientific journal, 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.

Exercise Capacity and Clinical Outcomes in Chronic Heart Failure Patients with Mild Tricuspid Regurgitation.
Kosuke Nakamura, Suguru Ishizaka, Kazunori Omote, Yutaro Yasui, Yoshifumi Mizuguchi, Sakae Takenaka, Yui Shimono, Ko Motoi, Hiroyuki Aoyagi, Yoji Tamaki, Sho Kazui, Yuki Takahashi, Kohei Saiin, Seiichiro Naito, Atsushi Tada, Yuta Kobayashi, Takuma Sato, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Journal of clinical medicine, 12, 23, 01 Dec. 2023, [International Magazine]
English, Scientific journal, AIM: The present study aimed to investigate the impact of mild tricuspid regurgitation (TR) on the exercise capacity or clinical outcomes in patients with chronic heart failure (CHF). METHODS AND RESULTS: The study enrolled 511 patients with CHF who underwent cardiopulmonary exercise testing (CPET) between 2013 and 2018. The primary outcome was a composite of heart failure hospitalization and death. Patients with mild TR (n = 324) or significant TR (moderate or greater; n = 60) displayed worse NHYA class and reduced exercise capacity on CPET than those with non-TR (n = 127), but these were more severely impaired in patients with significant TR. A total of 90 patients experienced events over a median follow-up period of 3.3 (interquartile range 0.8-5.5) years. Patients with significant TR displayed a higher risk of events, while patients with mild TR had a 3.0-fold higher risk of events than patients with non-TR (hazard ratio (HR) 3.01; 95% confidence interval (CI), 1.50-6.07). Multivariate Cox regression analysis showed that, compared with non-TR, mild TR was associated with increased adverse events, even after adjustment for co-variates (HR 2.97; 95% CI, 1.35-6.55). CONCLUSIONS: TR severity was associated with worse symptoms, reduced exercise capacity, and poor clinical outcomes. Even patients with mild TR had worse clinical characteristics than those with non-TR.

Differences in blood flow dynamics between balloon- and self-expandable valves in patients with aortic stenosis undergoing transcatheter aortic valve replacement.
Yuki Takahashi, Kiwamu Kamiya, Toshiyuki Nagai, Satonori Tsuneta, Noriko Oyama-Manabe, Takeshi Hamaya, Sho Kazui, Yutaro Yasui, Kohei Saiin, Seiichiro Naito, Yoshifumi Mizuguchi, Sakae Takenaka, Atsushi Tada, Suguru Ishizaka, Yuta Kobayashi, Kazunori Omote, Takuma Sato, Yasushige Shingu, Kohsuke Kudo, Satoru Wakasa, Toshihisa Anzai
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance, 25, 1, 60, 60, 26 Oct. 2023, [International Magazine]
English, Scientific journal, BACKGROUND: The differences in pre- and early post-procedural blood flow dynamics between the two major types of bioprosthetic valves, the balloon-expandable valve (BEV) and self-expandable valve (SEV), in patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR), have not been investigated. We aimed to investigate the differences in blood flow dynamics between the BEV and SEV using four-dimensional flow cardiovascular magnetic resonance (4D flow CMR). METHODS: We prospectively examined 98 consecutive patients with severe AS who underwent TAVR between May 2018 and November 2021 (58 BEV and 40 SEV) after excluding those without CMR because of a contraindication, inadequate imaging from the analyses, or patients' refusal. CMR was performed in all participants before (median interval, 22 [interquartile range (IQR) 4-39] days) and after (median interval, 6 [IQR 3-6] days) TAVR. We compared the changes in blood flow patterns, wall shear stress (WSS), and energy loss (EL) in the ascending aorta (AAo) between the BEV and SEV using 4D flow CMR. RESULTS: The absolute reductions in helical flow and flow eccentricity were significantly higher in the SEV group compared in the BEV group after TAVR (BEV: - 0.22 ± 0.86 vs. SEV: - 0.85 ± 0.80, P < 0.001 and BEV: - 0.11 ± 0.79 vs. SEV: - 0.50 ± 0.88, P = 0.037, respectively); there were no significant differences in vortical flow between the groups. The absolute reduction of average WSS was significantly higher in the SEV group compared to the BEV group after TAVR (BEV: - 0.6 [- 2.1 to 0.5] Pa vs. SEV: - 1.8 [- 3.5 to - 0.8] Pa, P = 0.006). The systolic EL in the AAo significantly decreased after TAVR in both the groups, while the absolute reduction was comparable between the groups. CONCLUSIONS: Helical flow, flow eccentricity, and average WSS in the AAo were significantly decreased after SEV implantation compared to BEV implantation, providing functional insights for valve selection in patients with AS undergoing TAVR. Our findings offer valuable insights into blood flow dynamics, aiding in the selection of valves for patients with AS undergoing TAVR. Further larger-scale studies are warranted to confirm the prognostic significance of hemodynamic changes in these patients.

心臓サルコイドーシス患者の免疫抑制療法開始後における心筋トロポニン値経時的評価の予後的意義　　　　　　　　　　　　　　　
數井 翔, 竹中 秀, 永井 利幸, 加藤 喜哉, 小森山 弘和, 小林 雄太, 高橋 昌寛, 神谷 究, 佐藤 琢真, 多田 篤司, 安井 悠太郎, 中井 陸運, 佐藤 隆博, 辻野 一三, 今野 哲, 安斉 俊久
日本サルコイドーシス/肉芽腫性疾患学会雑誌, 43, サプリメント号, 64, 64, 日本サルコイドーシス, Oct. 2023
Japanese

心臓サルコイドーシス患者におけるガドリニウム遅延造影心臓MRIとFDG-PETを用いた複合的画像評価の予後的意義　　　　　　　　　　　　　　　
數井 翔, 竹中 秀, 永井 利幸, 常田 慧徳, 加藤 喜哉, 小森山 弘和, 小林 雄太, 高橋 昌寛, 神谷 究, 天満 太郎, 佐藤 琢真, 多田 篤司, 安井 悠太郎, 中井 陸運, 佐藤 隆博, 辻野 一三, 工藤 與亮, 今野 哲, 安斉 俊久
日本サルコイドーシス/肉芽腫性疾患学会雑誌, 43, サプリメント号, 65, 65, 日本サルコイドーシス, Oct. 2023
Japanese

心臓サルコイドーシス患者の免疫抑制療法開始後における心筋トロポニン値経時的評価の予後的意義　　　　　　　　　　　　　　　
數井 翔, 竹中 秀, 永井 利幸, 加藤 喜哉, 小森山 弘和, 小林 雄太, 高橋 昌寛, 神谷 究, 佐藤 琢真, 多田 篤司, 安井 悠太郎, 中井 陸運, 佐藤 隆博, 辻野 一三, 今野 哲, 安斉 俊久
日本サルコイドーシス/肉芽腫性疾患学会雑誌, 43, サプリメント号, 64, 64, 日本サルコイドーシス, Oct. 2023
Japanese

心臓サルコイドーシス患者におけるガドリニウム遅延造影心臓MRIとFDG-PETを用いた複合的画像評価の予後的意義　　　　　　　　　　　　　　　
數井 翔, 竹中 秀, 永井 利幸, 常田 慧徳, 加藤 喜哉, 小森山 弘和, 小林 雄太, 高橋 昌寛, 神谷 究, 天満 太郎, 佐藤 琢真, 多田 篤司, 安井 悠太郎, 中井 陸運, 佐藤 隆博, 辻野 一三, 工藤 與亮, 今野 哲, 安斉 俊久
日本サルコイドーシス/肉芽腫性疾患学会雑誌, 43, サプリメント号, 65, 65, 日本サルコイドーシス, Oct. 2023
Japanese

Impact of Cardiac Power Output on Exercise Capacity and Clinical Outcome in Patients With Chronic Heart Failure.
Yui Shimono, Suguru Ishizaka, Kazunori Omote, Kosuke Nakamura, Yutaro Yasui, Yoshifumi Mizuguchi, Sakae Takenaka, Hiroyuki Aoyagi, Yoji Tamaki, Takuma Sato, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
The American journal of cardiology, 206, 4, 11, 05 Sep. 2023, [International Magazine]
English, Scientific journal, Less data are available regarding the impact of cardiac power output on exercise capacity or clinical outcome in patients with chronic heart failure (CHF). The study enrolled 280 consecutive patients with CHF referred for cardiopulmonary exercise testing and right-sided heart catheterization between 2013 and 2018. The primary outcome was composite of heart failure hospitalization or death. Cardiac power output was calculated as (mean arterial pressure × CO) ÷ 451. Patients with low cardiac power output (<0.53 W, n = 99) were older and had a higher brain natriuretic peptide level than patients with high cardiac power output (≥0.53W, n = 181). Cardiac power output was correlated with peak oxygen consumption (peak V̇O2), peak workload achievement, and ventilatory efficiency (V̇E/V̇CO2 slope) in cardiopulmonary exercise testing, whereas each of cardiac output or mean arterial pressure was not. There were 48 patients with events over a median follow-up period of 3.5 (interquartile range 1.0 to 6.0) years. Patients with low cardiac power output had about a 2-fold higher risk of events than those with a high cardiac power output (hazard ratio 1.97, 95% confidence interval 1.12 to 3.48). In the multivariable Cox regression, a 0.1-W decrease in cardiac power output was associated with 19% increased adverse events (hazard ratio 0.81, 95% confidence interval 0.67 to 0.99). In conclusion, cardiac power output was associated with reduced exercise capacity and poor clinical outcome, suggesting that cardiac power output is useful for risk stratification in patients with CHF. Further study is required to identify therapies targeting cardiac power output to improve the exercise capacity or clinical outcome in patients with CHF.

Association of longitudinal cardiac troponin trajectory with adverse events in patients with cardiac sarcoidosis.
Sho Kazui, Sakae Takenaka, Toshiyuki Nagai, Yoshiya Kato, Hirokazu Komoriyama, Yuta Kobayashi, Akinori Takahashi, Kiwamu Kamiya, Takuma Sato, Atsushi Tada, Yutaro Yasui, Michikazu Nakai, Takahiro Sato, Ichizo Tsujino, Satoshi Konno, Toshihisa Anzai
International journal of cardiology, 389, 131268, 131268, 15 Aug. 2023, [International Magazine]
English, Scientific journal, BACKGROUND: Although high-sensitivity cardiac troponins may be sensitive and easily repeatable markers of disease activity in patients with cardiac sarcoidosis (CS), the association between longitudinal cardiac troponin trajectory and adverse events remains unclear. This study aimed to clarify whether longitudinal cardiac troponin levels were associated with adverse events in patients with CS. METHODS: We examined 63 consecutive CS-initiated prednisolone (PSL) patients with available longitudinal high-sensitivity cardiac troponin T (cTnT) data between December 2013 and March 2023. The area under the cTnT trajectory, which reflected cumulative cTnT release, was calculated to assess the association between longitudinal cTnT levels and adverse events. Patients were divided into two groups according to the median area under the cTnT trajectory per month. The primary outcome was a composite of sustained ventricular tachycardia or fibrillation, worsening heart failure, and sudden cardiac death (SCD). RESULTS: In total, 463 cTnT measurements were collected over a median follow-up period of 30.4 (interquartile range [IQR] 15.6-34.2) months. The primary outcome was observed in 12 (19%) patients. A higher area under the cTnT trajectory was significantly associated with an increased incidence of the primary outcome (P = 0.027), while cTnT levels before and one month after initiation of PSL, and these changes were not related to adverse events (P = 0.179, 0.096, and 0.95, respectively). CONCLUSIONS: Longitudinal cTnT trajectory following PSL initiation was associated with adverse cardiac events in patients with CS, suggesting that longitudinal measurement of cTnT would be useful for the early identification of high-risk patients.

Association between Non-Lipid Residual Risk Factors and Cardiovascular Events in Patients with Stable Coronary Artery Disease Treated with Pitavastatin: An Observation from the REAL-CAD Study.
Kiwamu Kamiya, Makoto Takei, Toshiyuki Nagai, Toru Miyoshi, Hiroshi Ito, Yoshihiro Fukumoto, Hitoshi Obara, Tatsuyuki Kakuma, Ichiro Sakuma, Hiroyuki Daida, Satoshi Iimuro, Hiroaki Shimokawa, Takeshi Kimura, Ryozo Nagai, Toshihisa Anzai
Journal of atherosclerosis and thrombosis, 11 Aug. 2023, [Domestic magazines]
English, Scientific journal, AIMS: We aimed to investigate the association between non-lipid residual risk factors and cardiovascular events in patients with stable coronary artery disease (CAD) who achieved low-density lipoprotein cholesterol (LDL-C) ＜100 mg/dL from the Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study. METHODS: The REAL-CAD study was a prospective, multicenter, open-label trial. As a sub-study, we examined the prognostic impact of non-lipid residual risk factors, including blood pressure, glucose level, and renal function, in patients who achieved LDL-C ＜100 mg/dL at 6 months after pitavastatin therapy. Each risk factor was classified according to severity. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unstable angina requiring emergency hospitalization. RESULTS: Among 8,743 patients, the mean age was 68±8.2 years, and the mean LDL-C level was 84.4±18 mg/dL. After adjusting for the effects of confounders, an estimated glomerular filtration rate (eGFR) ≤ 60 mL/min/1.73 m2 showed the highest risk of the primary outcome (hazard ratio [HR] 1.92; 95% confidence interval [CI] 1.45-2.53). The combination of eGFR ≤ 60 and hemoglobin A1c (HbA1c) ≥ 6.0% also showed the highest risk of all-cause death (HR, 2.42; 95% CI, 1.72-3.41). CONCLUSIONS: In patients with stable CAD treated with pitavastatin and who achieved guidelines-directed levels of LDL-C, eGFR and HbA1c were independently associated with adverse events, suggesting that renal function and glycemic control could be residual non-lipid therapeutic targets after statin therapy.

Cost-effective analysis of transcatheter aortic valve replacement in patients with severe symptomatic aortic stenosis: A prospective multicenter study.
Makoto Amaki, Kensuke Moriwaki, Michikazu Nakai, Tetsuhiro Yamano, Atsushi Okada, Hideaki Kanzaki, Masaki Izumo, Hiroki Usuku, Tetsuari Onishi, Toshiyuki Nagai, Yoshihiro Miyamoto, Tomoyuki Fujita, Hiroya Kawai, Yoshihiro Akashi, Kenichi Tsujita, Satoaki Matoba, Junjiro Kobayashi, Chisato Izumi, Toshihisa Anzai
Journal of cardiology, 03 Aug. 2023, [International Magazine]
English, Scientific journal, BACKGROUND: Transcatheter aortic valve replacement (TAVR) for severe symptomatic aortic stenosis (AS) does not benefit all patients. We performed a prospective multicenter study to investigate the cost-effectiveness of TAVR in a Japanese cohort. METHODS AND RESULTS: We prospectively enrolled 110 symptomatic patients with severe AS who underwent TAVR from five institutions. The quality of life measurement (QOL) was performed for each patient before and at 6 months after TAVR. Patients without an improvement in QOL at 6 months after TAVR were defined as non-responders. Pre-TAVR higher QOL, higher clinical frailty scale predicted the non-responders. Three models, 1) conservative treatment for all patients strategy, 2) TAVR for all patients strategy, and 3) TAVR for a selected patient strategy who is expected to be a responder, were simulated. Lifetime cost-effectiveness was estimated using incremental cost-effectiveness ratio (ICER) and cost per quality-adjusted life-year (QALY) gained. In comparison to conservative therapy for all patients, ICER was estimated to be 5,765,800 yen/QALY for TAVR for all patients and 2,342,175 yen/QALY for TAVR for selected patient strategy patients, which is less than the commonly accepted ICER threshold of 5,000,000 yen/QALY. CONCLUSIONS: TAVR for selected patient strategy model is more cost-effective than TAVR for all patient strategy without reducing QOL in the Japanese healthcare system. TAVR for selected patient strategy has potential benefit for optimizing the TAVR treatment in patients with high frailty and may direct our resources toward beneficial interventions.

Efficacy of azilsartan on left ventricular diastolic dysfunction compared with candesartan: J-TASTE randomized controlled trial.
Shin Ito, Hiroyuki Takahama, Masanori Asakura, Yukio Abe, Masayoshi Ajioka, Toshihisa Anzai, Takuo Arikawa, Takaharu Hayashi, Yorihiko Higashino, Shinya Hiramitsu, Noriaki Iwahashi, Chisato Izumi, Kazuo Kimura, Koichiro Kinugawa, Hidetaka Kioka, Young-Jae Lim, Ken Matsuoka, Satoshi Matsuoka, Hirohiko Motoki, Sunao Nakamura, Takafumi Nakayama, Akihiro Nomura, Taishi Sasaoka, Shin Takiuchi, Shigeru Toyoda, Tomoya Ueda, Tetsuya Watanabe, Akira Yamada, Masayoshi Yamamoto, Takashi Sozu, Masafumi Kitakaze
Scientific reports, 13, 1, 12517, 12517, 02 Aug. 2023, [International Magazine]
English, Scientific journal, Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, azilsartan may improve the left ventricular (LV) diastolic function in patients with hypertension and either HFpEF or HF with mildly reduced ejection fraction (HFmrEF) more than candesartan. In this randomized, open-label trial, we randomly assigned 193 hypertensive patients with HF and LV ejection fraction ≥ 45% to 20 mg of azilsartan (n = 95) or 8 mg of candesartan (n = 98), once daily for 48 weeks. After the initiation of treatment, changes in the doses of the study drugs were permitted based on the patient's conditions, including blood pressure (median dose at 48 weeks: azilsartan 20.0 mg/day, candesartan 8.0 mg/day). The primary endpoint was the baseline-adjusted change in the ratio of peak early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e') (E/e'). Adjusted least-squares mean (LSM) change in E/e' was - 0.8 (95% confidence interval [CI] - 1.49 to - 0.04) in the azilsartan group and 0.2 (95% CI - 0.49 to 0.94) in the candesartan group, providing the LSM differences of - 1.0 (95% CI - 2.01 to 0.03, P = 0.057). The median change in left atrial volume index was - 2.7 mL/m2 with azilsartan vs 1.4 mL/m2 with candesartan (P = 0.091). The frequency of adverse events related to hypotension and hyperkalemia did not differ between the groups. The current study did not provide strong evidence that azilsartan improves LV diastolic dysfunction, and further confirmatory study is required.

Increased Piezo1 expression in myofibroblasts in patients with symptomatic carotid atherosclerotic plaques undergoing carotid endarterectomy: A pilot study.
Takao Konishi, Kenji Kamiyama, Toshiaki Osato, Tetsuyuki Yoshimoto, Takeshi Aoki, Toshihisa Anzai, Shinya Tanaka
Vascular, 17085381231192380, 17085381231192380, 27 Jul. 2023, [International Magazine]
English, Scientific journal, OBJECTIVES: We aimed to investigate Piezo1 expression in myofibroblasts in symptomatic and asymptomatic patients undergoing carotid endarterectomy and its relationship with atherosclerotic plaque formation. METHODS: This cross-sectional study analyzed carotid plaques of 17 randomly selected patients who underwent carotid endarterectomy from May 2015 to August 2017. In total, 51 sections (the most stenotic lesion, and the sections 5-mm proximal and distal) stained with hematoxylin-eosin and elastica-Masson were examined. Immunohistochemistry was performed using antibodies to Piezo1. The Piezo1 score of a section was calculated semiquantitatively, averaged across 30 randomly selected myofibroblasts in the fibrous cap of the plaque. RESULTS: Of 17 patients (mean age: 74.2 ± 7.1 years), 15 were men, 9 had diabetes mellitus, and 13 had hypertension. Symptomatic patients had higher mean Piezo1 score than asymptomatic patients (1.78 ± 0.23 vs 1.34 ± 0.17, p < .001). Univariate linear regression analyses suggested an association between plaque rupture, thin-cap fibroatheroma and microcalcifications and the Piezo1 score (p = .001, .008, and 0.003, respectively). CONCLUSIONS: Increased Piezo1 expression of myofibroblasts may be associated with atherosclerotic carotid plaque instability. Further study is warranted to support this finding.

Relationship between Canagliflozin, Sodium Glucose Cotransporter 2 Inhibitor, and Hematopoietic Effects in Patients with Diabetes and Mild Heart Failure: Results from the CANDLE Trial
Daisaku Nakatani, Tomoharu Dohi, Shungo Hikoso, Atsushi Tanaka, Mamoru Nanasato, Wataru Shimizu, Koichi Node, Yasushi Sakata, Masayoshi Ajioka, Junya Ako, Rie Amano, Toshihisa Anzai, Mitsutoshi Asai, Kaoru Dohi, Kazuo Eguchi, Kenichi Eshima, Shinya Fujiki, Masashi Fujita, Shinya Hiramitsu, Satoshi Hoshide, Akihiko Hoshino, Yuki Ikeda, Yumi Ikehara, Takayuki Inomata, Teruo Inoue, Katsuhisa Ishii, Nobukazu Ishizaka, Masaaki Ito, Noriaki Iwahashi, Katsuomi Iwakura, Toshiaki Kadokami, Haruo Kamiya, Takahiro Kanbara, Yumiko Kanzaki, Ken Kashimura, Keisuke Kida, Kazuo Kimura, Satoru Kishi, Shuichi Kitada, Akihiro Kiyosue, Kazuhisa Kodama, Takayuki Kojima, Takumi Kondo, Yoshiaki Kubota, Kenya Kusunose, Noritaka Machii, Kazuo Matsunaga, Yasuto Matsuo, Yashushi Matsuzawa, Takeshi Mikami, Toru Minamino, Takahiro Nagai, Yasuko Nagano, Masashi Nagumo, Ikuko Nakamura, Katsunori Nakamura, Hiriyuki Naruse, Masami Nishino, Shinichi Niwano, Mitsutoshi Oguri, Nobuyuki Ohte, Masayoshi Oikawa, Takahiro Okumura, Masanori Okumura, Katsuya Onishi, Yukio Ozaki, Kan Saito, Tomohiro Sakamoto, Masashi Sakuma, Hisakuni Sekino, Kazuki Shiina, Michio Shimabukuro, Makoto Suzuki, Kunihiro Suzuki, Hiroyuki Takahama, Naohiko Takahashi, Yasuchika Takeishi, Shunsuke Tamaki, Akihiro Tanaka, Syuzo Tanimoto, Hiroki Teragawa, Tomoyuki Tobushi, Takafumi Toita, Kotaro Tokuda, Hirofumi Tomiyama, Hiroyuki Tsutsui, Hiroki Uehara, Masaaki Uematsu, Hirotaka Watada, Kazuyuki Yahagi, Takahisa Yamada, Hirotsugu Yamada, Tatsuya Yoshida, Akiomi Yoshihisa
Journal of Cardiovascular Pharmacology, 82, 1, 61, 68, 19 Jul. 2023
Scientific journal

Paradoxical increase in global longitudinal strain by handgrip exercise despite left ventricular diastolic dysfunction.
Ko Motoi, Hiroyuki Iwano, Suguru Ishizaka, Kosuke Nakamura, Yoji Tamaki, Hiroyuki Aoyagi, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Michito Murayama, Sanae Kaga, Toshihisa Anzai
Echocardiography (Mount Kisco, N.Y.), 40, 8, 810, 821, 14 Jul. 2023, [International Magazine]
English, Scientific journal, BACKGROUND: Although global longitudinal strain (GLS) is recognized as a sensitive marker of intrinsic left ventricular (LV) dysfunction, its afterload dependency has also been pointed. We hypothesized that decrease in GLS during handgrip exercise could be more sensitive marker of intrinsic myocardial dysfunction. METHODS: Handgrip exercise-stress echocardiography was performed in 90 cardiovascular disease patients with preserved LV ejection fraction. LV diastolic function was graded according to the guidelines. Diastolic wall stress (DWS) and ratio of left atrial (LA) volume index to late-diastolic mitral annular velocity (LAVI/a') were measured at rest as LV stiffness. As well, LA strains were measured to assess LA function. GLS was expressed as absolute value and significant changes in GLS by handgrip exercise was defined as changes over prespecified mean absolute test-retest variability (2.65%). RESULTS: While mean value of GLS did not change by the exercise, substantial patients showed significant changes in GLS: decreased (group I, n = 28), unchanged (group II, n = 34), and increased (group III, n = 28). Unexpectedly, patients in group I did not show any clinical and echocardiographic characteristics, while those in group III were characterized by elevated natriuretic peptide levels, blunted heart rate response to handgrip exercise, and advanced LV diastolic dysfunction. Multivariable analyses revealed that DWS, left atrial booster strain, and grade II or more diastolic dysfunction determined the increase in GLS even after adjustment for elevated natriuretic peptides and the changes in heart rate by the exercise. CONCLUSION: In contrast to our hypothesis, paradoxical increase in GLS by handgrip exercise could be associated with advanced LV diastolic dysfunction in cardiovascular patients with preserved LV ejection fraction. Our findings suggest that HG exercise for heart failure patients does not enhance the afterload straightforward, resulting in variable changes of GLS according to the individual conditions.

Prognostic Value of Liver Fibrotic Markers in Patients With Heart Failure.
Atsushi Tada, Toshiyuki Nagai, Yoshiya Kato, Noriko Oyama-Manabe, Satonori Tsuneta, Michikazu Nakai, Yutaro Yasui, Sho Kazui, Yuki Takahashi, Kohei Saiin, Seiichiro Naito, Sakae Takenaka, Yoshifumi Mizuguchi, Yuta Kobayashi, Suguru Ishizaka, Kazunori Omote, Takuma Sato, Takao Konishi, Kiwamu Kamiya, Kohsuke Kudo, Toshihisa Anzai
The American journal of cardiology, 200, 115, 123, 10 Jun. 2023, [International Magazine]
English, Scientific journal, Several liver fibrotic markers are associated with prognosis in patients with heart failure (HF). However, the optimal markers for outcome prediction remain unclear. This study aimed to simultaneously investigate the prognostic value of liver fibrotic markers and the associations between these markers and clinical parameters in patients with HF without organic liver disease. We prospectively examined 211 consecutive patients with chronic HF between April 2018 and August 2021, excluding those with organic liver disease, using liver magnetic resonance imaging and ultrasound. A total of 7 representative liver fibrotic markers were measured in all patients. The primary outcome of interest was the composite of all-cause death and hospitalization for worsening HF. During a median follow-up period of 747 (interquartile range 465 to 1,042) days, the primary outcome occurred in 45 patients. Patients with higher hyaluronic acid and type III procollagen N-terminal peptide (P-III-P) levels showed a significantly higher incidence of the primary outcome than those without (p <0.001 and p = 0.005, respectively). The multivariable Cox regression analysis revealed that hyaluronic acid and P-III-P levels were independently associated with the risk of adverse events (hazard ratio 1.84, 95% confidence interval 1.18 to 2.87 and hazard ratio 2.89, 95% confidence interval 1.32 to 6.34, respectively) even after adjustment for a mortality prediction model, whereas the other 5 markers were not associated with the primary outcome. In conclusion, among the representative liver fibrotic markers, hyaluronic acid and P-III-P might be the optimal markers for outcome prediction in patients with HF.

Leadless Pacemaker With Acute but Transient Elevation of Lead Impedance and Pacing Threshold.
Hikaru Hagiwara, Junpei Morimoto, Toshifumi Tamura, Akinori Takahashi, Hirokazu Komoriyama, Yoshiya Kato, Toshihisa Anzai
CJC open, 5, 6, 412, 414, Jun. 2023, [International Magazine]
English

Application of an echocardiographic scoring system of left ventricular filling pressure to diagnose acute heart failure in patients complaining dyspnea.
Yoji Tamaki, Hiroyuki Iwano, Michito Murayama, Suguru Ishizaka, Ko Motoi, Hiroyuki Aoyagi, Kosuke Nakamura, Mana Goto, Yukino Suzuki, Shinobu Yokoyama, Hisao Nishino, Masahiro Nakabachi, Sanae Kaga, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Journal of cardiology, 82, 1, 62, 68, 27 Apr. 2023, [International Magazine]
English, Scientific journal, BACKGROUND: Dyspnea is a common symptom in acute heart failure (AHF) patients. Although an accurate and rapid diagnosis of AHF is essential to improve prognosis, estimation of left ventricular (LV) filling pressure (FP) remains challenging, especially for noncardiologists. We evaluated the usefulness of a recently-proposed parameter of LV FP, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score, to detect AHF in patients complaining of dyspnea. METHODS: Echocardiography and lung ultrasonography (LUS) were performed in 121 consecutive patients (68 ± 14 years old, 75 males) presenting with dyspnea. The VMT score was determined from the atrioventricular valve opening phase (tricuspid valve first: 0, simultaneous: 1, mitral valve first: 2) and inferior vena cava dilatation (absent: 0, present: 1), and VMT ≥2 was judged as positive. LUS was performed with the 8 zones method and judged as positive if 3 or more B-lines were observed in bilateral regions. The AHF diagnosis was performed by certified cardiologists according to recent guidelines. RESULTS: Of the 121 patients, 33 were diagnosed with AHF. The sensitivity and specificity for diagnosing AHF were 64 % and 84 % for LUS and 94 % and 88 % for VMT score. In logistic regression analysis, VMT score showed a significantly higher c-index than LUS (0.91 vs 0.74, p = 0.002). In multivariable analyses, VMT score was associated with AHF independently of clinically relevant covariates and LUS. In addition, serial assessment of VMT score followed by LUS provided a diagnostic flow chart to diagnose AHF (VMT 3: AHF definitive, VMT 2 and LUS positive: AHF highly suspicious; VMT 2 and LUS negative: further investigation is needed; VMT ≤ 1: AHF rejected). CONCLUSIONS: VMT score showed high diagnostic accuracy in diagnosing AHF. Combined assessment of the VMT score and LUS could become a reliable strategy for diagnosis of AHF by non-cardiologists.

Heart failure with preserved ejection fraction phenogroup classification using machine learning
Atsushi Kyodo, Koshiro Kanaoka, Ayaka Keshi, Maki Nogi, Kazutaka Nogi, Satomi Ishihara, Daisuke Kamon, Yukihiro Hashimoto, Yasuki Nakada, Tomoya Ueda, Ayako Seno, Taku Nishida, Kenji Onoue, Tsuneari Soeda, Rika Kawakami, Makoto Watanabe, Toshiyuki Nagai, Toshihisa Anzai, Yoshihiko Saito
ESC Heart Failure, 10, 3, 2019, 2030, Wiley, 12 Apr. 2023
Scientific journal

Vieussens' arterial ring forming a fistula that drains into the pulmonary artery through an aneurysm.
Hikaru Hagiwara, Akinori Takahashi, Hirokazu Komoriyama, Yoshiya Kato, Toshihisa Anzai
European heart journal. Cardiovascular Imaging, 04 Apr. 2023, [International Magazine]
English, Scientific journal

静脈血流速度波形分析に基づく右房圧推定に肝静脈と上大静脈のどちらが優れるか　　　　　　　　　　　　　　　
村山 迪史, 加賀 早苗, 境田 ひな, 小野田 愛梨, 中鉢 雅大, 西野 久雄, 横山 しのぶ, 石坂 傑, 岩野 弘幸, 安斉 俊久
超音波医学, 50, Suppl., S740, S740, (公社)日本超音波医学会, Apr. 2023
Japanese

静脈血流速度波形分析に基づく右房圧推定に肝静脈と上大静脈のどちらが優れるか　　　　　　　　　　　　　　　
村山 迪史, 加賀 早苗, 境田 ひな, 小野田 愛梨, 中鉢 雅大, 西野 久雄, 横山 しのぶ, 石坂 傑, 岩野 弘幸, 安斉 俊久
超音波医学, 50, Suppl., S740, S740, (公社)日本超音波医学会, Apr. 2023
Japanese

Multimodal Imaging of Constrictive Pericarditis Induced by Long-term Pergolide Treatment for Parkinson's Disease.
Hiroyuki Aoyagi, Shingo Tsujinaga, Yuki Takahashi, Seiichiro Naito, Takuma Sato, Takuya Otsuka, Yoji Tamaki, Ko Motoi, Suguru Ishizaka, Yasuyuki Chiba, Kiwamu Kamiya, Hiroyuki Iwano, Toshiyuki Nagai, Satoru Wakasa, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 31 Mar. 2023, [Domestic magazines]
English, Scientific journal, We herein report the first case of constrictive pericarditis (CP) induced by long-term pergolide treatment for Parkinson's disease that was assessed using multimodal imaging in a 72-year-old patient with leg edema and dyspnea. The patient was correctly diagnosed with CP using multimodal imaging and successfully treated with pericardiectomy. The treatment history of Parkinson's disease and pathological findings of the removed pericardium suggested that long-term pergolide was the cause of CP. Properly recognizing pergolide as the cause of CP and accurately diagnosing CP using multimodal imaging may contribute to the early detection and treatment of pergolide-induced CP.

Impact of COVID-19 pandemic on emergency medical system and management strategies in patients with acute coronary syndrome.
Kohei Saiin, Sakae Takenaka, Toshiyuki Nagai, Akinori Takahashi, Yoshifumi Mizuguchi, Takao Konishi, Toshihisa Anzai, Daisuke Hotta, Mitsunori Kamigaki, Seiji Yamazaki, Tsutomu Fujita, Takehiro Yamashita, Kandoh Kawahatsu, Takashi Suzuki, Yoichi Nozaki, Taku Sakurada, Takashi Takenaka, Yasumi Igarashi, Takao Makino
Scientific reports, 13, 1, 5120, 5120, 29 Mar. 2023, [International Magazine]
English, Scientific journal, The global coronavirus disease-2019 (COVID-19) pandemic is associated with reduced rate of percutaneous coronary intervention (PCI). However, there were a few data showing how emergency medical system (EMS) and management strategies for acute coronary syndrome (ACS) changed during the pandemic. We sought to clarify changes on characteristics, treatments, and in-hospital mortality of patients with ACS transported via EMS between pre- and post-pandemic. We examined consecutive 656 patients with ACS admitted to Sapporo City ACS Network Hospitals between June 2018 and November 2021. The patients were divided into pre- and post-pandemic groups. The number of ACS hospitalizations declined significantly during the pandemic (proportional reduction 66%, coefficient -0.34, 95% CI -0.50 to -0.18, p < 0.001). The median time from an EMS call to hospital was significantly longer in post-pandemic group than in pre-pandemic group (32 [26-39] vs. 29 [25-36] min, p = 0.008). There were no significant differences in the proportion of patients with ACS receiving PCI, and in-hospital mortality between the groups. The COVID-19 pandemic had a significant impact on EMS and management in patients with ACS. Although a significant decline was observed in ACS hospitalizations, the proportion of patients with ACS receiving emergency PCI remained during the pandemic.

Impact of right ventricular stiffness on discordance between hemodynamic parameter and regurgitant volume in patients with pulmonary regurgitation.
Ko Motoi, Hiroyuki Iwano, Satonori Tsuneta, Suguru Ishizaka, Yoji Tamaki, Hiroyuki Aoyagi, Kosuke Nakamura, Michito Murayama, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Sanae Kaga, Atsuhito Takeda, Toshihisa Anzai
The international journal of cardiovascular imaging, 39, 6, 1133, 1142, 17 Mar. 2023, [International Magazine]
English, Scientific journal, BACKGROUND: Accurate detection of significant pulmonary regurgitation (PR) is critical in management of patients after right ventricular (RV) outflow reconstruction in Tetralogy of Fallot (TOF) patients, because of its influence on adverse outcomes. Although pressure half time (PHT) of PR velocity is one of the widely used echocardiographic markers of the severity, shortened PHT is suggested to be seen in conditions with increased RV stiffness with mild PR. However, little has been reported about the exact characteristics of patients showing discrepancy between PHT and PR volume in this population. METHODS: Echocardiography and cardiac magnetic resonance imaging (MRI) were performed in 74 TOF patients after right ventricular outflow tract (RVOT) reconstruction [32 ± 10 years old]. PHT was measured from the continuous Doppler PR flow velocity profile and PHT < 100 ms was used as a sign of significant PR. Presence of end-diastolic RVOT forward flow was defined as RV restrictive physiology. By using phase-contrast MRI, forward and regurgitant volumes through the RVOT were measured and regurgitation fraction was calculated. Significant PR was defined as regurgitant fraction ≥ 25%. RESULTS: Significant PR was observed in 54 of 74 patients. While PHT < 100 ms well predicted significant PR with sensitivity of 96%, specificity of 52%, and c-index of 0.72, 10 patients showed shortened PHT despite regurgitant fraction < 25% (discordant group). Tricuspid annular plane systolic excursion and left ventricular (LV) ejection fraction were comparable between discordant group and patients showing PHT < 100 ms and regurgitant fraction ≥ 25% (concordant group). However, discordant group showed significantly smaller mid RV diameter (30.7 ± 4.5 vs. 39.2 ± 7.3 mm, P < 0.001) and higher prevalence of restrictive physiology (100% vs. 42%, P < 0.01) than concordant group. When mid RV diameter ≥ 32 mm and presence of restrictive physiology were added to PHT, the predictive value was significantly improved (sensitivity: 81%, specificity: 90%, and c-index: 0.89, P < 0.001 vs. PHT alone by multivariable logistic regression model). CONCLUSION: Patients with increased RV stiffness and non-enlarged right ventricle showed short PHT despite mild PR. Although it has been expected, this was the first study to demonstrate the exact characteristics of patients showing discrepancy between PHT and PR volume in TOF patients after RVOT reconstruction.

JCS 2023 Guideline on the Diagnosis and Treatment of Myocarditis.
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 : official journal of the Japanese Circulation Society, 87, 5, 674, 754, 10 Mar. 2023, [Domestic magazines]
English, Scientific journal

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, Mar. 2023
English

大動脈弁狭窄症患者に対する左室充満圧の心エコースコアリングシステムの適用(Application of an Echocardiographic Scoring System of Left Ventricular Filling Pressure for Patients with Aortic Stenosis)　　　　　　　　　　　　　　　
青柳 裕之, 岩野 弘幸, 後藤 真奈, 鈴木 ゆき乃, 村山 迪史, 横山 しのぶ, 西野 久雄, 中鉢 雅大, 中村 公亮, 玉置 陽生, 本居 昂, 石坂 傑, 加賀 早苗, 神谷 究, 永井 利幸, 安斉 俊久
日本循環器学会学術集会抄録集, 87回, PJ065, 2, (一社)日本循環器学会, Mar. 2023
English

心不全患者における複数の超音波指標を組み合わせたうっ血肝診断モデルの確立　　　　　　　　　　　　　　　
小野田 愛梨, 村山 迪史, 加賀 早苗, 中鉢 雅大, 横山 しのぶ, 西野 久雄, 石坂 傑, 本居 昴, 青柳 裕之, 玉置 陽生, 中村 公亮, 岩野 弘幸, 安斉 俊久
日本循環器学会学術集会抄録集, 87回, CO1, 3, (一社)日本循環器学会, Mar. 2023
Japanese

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, Mar. 2023
Scientific journal

Impact of right ventricular reserve on exercise capacity and quality of life in patients with left ventricular assist device.
Sakae Takenaka, Takuma Sato, Toshiyuki Nagai, Kazunori Omote, Yuta Kobayashi, Kiwamu Kamiya, Takao Konishi, Atsushi Tada, Yoshifumi Mizuguchi, Yuki Takahashi, Seiichiro Naito, Kohei Saiin, Suguru Ishizaka, Satoru Wakasa, Toshihisa Anzai
American journal of physiology. Heart and circulatory physiology, 324, 3, H355-H363, 01 Mar. 2023, [International Magazine]
English, Scientific journal, Although measuring right ventricular (RV) function during exercise is more informative than assessing it at rest, the relationship between RV reserve function, exercise capacity, and health-related quality of life (HRQoL) in patients with left ventricular assist devices (LVAD) remains unresolved. We aimed to investigate whether RV reserve assessed by the change in RV stroke work index (RVSWI) during exercise is correlated with exercise capacity and HRQoL in patients with LVAD. We prospectively assessed 24 consecutive patients with LVAD who underwent invasive right heart catheterization in the supine position. Exercise capacity and HRQoL were assessed using the 6-min walk distance (6 MWD) and peak oxygen consumption (V̇o2) in cardiopulmonary exercise testing, and the EuroQol visual analog scale (EQ-VAS), respectively. The patients were divided into two groups according to the median ΔRVSWI (change from rest to peak exercise). Patients with lower ΔRVSWI had significantly lower changes in cardiac index and absolute value of RV dP/dt than those with higher ΔRVSWI. The ΔRVSWI was positively correlated with 6 MWD (r = 0.59, P = 0.003) and peak V̇o2 (r = 0.56, P = 0.006). In addition, ΔRVSWI was positively correlated with the EQ-VAS (r = 0.44, P = 0.030). In contrast, there was no significant correlation between RVSWI at rest and 6 MWD (r = -0.34, P = 0.88), peak V̇o2 (r = 0.074, P = 0.74), or EQ-VAS (r = 0.127, P = 0.56). Our findings suggest that the assessment of RV reserve function is useful for risk stratification in patients with LVAD.NEW & NOTEWORTHY The change in right ventricular stroke work index (RVSWI) during exercise, not RVSWI at rest, was associated with exercise capacity and HRQoL. Our findings suggest that the assessment of change in RVSWI during exercise as a surrogate of RV reserve function may aid in risk stratification of patients with LVAD.

Prognostic Significance of Peak Workload-to-Weight Ratio by Cardiopulmonary Exercise Testing in Chronic Heart Failure.
Yutaro Yasui, Kosuke Nakamura, Kazunori Omote, Suguru Ishizaka, Sakae Takenaka, Yoshifumi Mizuguchi, Yui Shimono, Sho Kazui, Yuki Takahashi, Kohei Saiin, Seiichiro Naito, Atsushi Tada, Yuta Kobayashi, Takuma Sato, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
The American journal of cardiology, 193, 37, 43, 01 Mar. 2023, [International Magazine]
English, Scientific journal, The prognostic impact of peak workload-to-weight ratio (PWR) during cardiopulmonary exercise testing (CPET) and its determinants in patients with chronic heart failure (CHF) are not well understood. Consecutive 514 patients with CHF referred for CPET at the Hokkaido University Hospital between 2013 and 2018 were identified. The primary outcome was a composite of hospitalization because of worsening heart failure and death. PWR was calculated as peak workload normalized to body weight (W/kg) by CPET. Patients with low PWR (cut-off median 1.38 [W/kg], n = 257) were older and more anemic than those with high PWR (n = 257). In CPET, patients with low PWR displayed reduced peak oxygen consumption and impaired ventilatory efficiency compared with those with high PWR, whereas the peak respiratory exchange ratio was not significantly different between the 2 groups. There were 89 patients with events over a median follow-up period of 3.3 (interquartile range 0.8 to 5.5) years. The incidence of composite events was significantly higher in patients with low PWR than in those with high PWR (log-rank p <0.0001). In the multivariable Cox regression, lower PWR was associated with adverse events (hazard ratio 0.31, 95% confidence interval 0.13 to 0.73, p = 0.008). Low hemoglobin concentration was strongly related to impaired PWR (β coefficient = 0.43, per 1 g/100 ml increased, p <0.0001). In conclusion, PWR was associated with worse clinical outcomes, where blood hemoglobin was strongly related to PWR. Further study is required to identify therapies targeting peak workload achievements in exercise stress tests to improve the outcome in patients with CHF.

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, 06 Feb. 2023
Scientific journal, 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, 13 Jan. 2023, [Domestic magazines]
English, Scientific journal, 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, 06 Jan. 2023, [International Magazine]
English, Scientific journal, 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.

Plans for the Circulation Journal.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 88, 1, 1, 1, 2023, [Domestic magazines]
English, Scientific journal

Association of coronary plaque morphology with inflammatory biomarkers and target lesion revascularization in patients with chronic coronary syndrome: an optical coherence tomography study.
Kohei Saiin, Takao Konishi, Sho Kazui, Yutaro Yasui, Yuki Takahashi, Seiichiro Naito, Sakae Takenaka, Yoshifumi Mizuguchi, Atsushi Tada, Yuta Kobayashi, Yoshiya Kato, Kazunori Omote, Takuma Sato, Kiwamu Kamiya, Toshiyuki Nagai, Shinya Tanaka, Toshihisa Anzai
American journal of cardiovascular disease, 13, 5, 309, 319, 2023, [International Magazine]
English, Scientific journal, BACKGROUND: The characteristics of high-risk coronary atherosclerosis evaluated using optical coherence tomography (OCT) can have a prognostic role. Inflammatory biomarkers may be related to the severity of coronary artery disease. This study investigated the association of high-risk morphological features of coronary plaques on OCT with circulating levels of inflammatory biomarkers and target lesion revascularization (TLR). MATERIALS AND METHODS: We prospectively analyzed the data of 30 consecutive patients with chronic coronary syndrome who underwent percutaneous coronary intervention (PCI) using OCT. The levels of interleukin-6, tumor necrosis factor-alpha, high-sensitivity C-reactive protein, pentraxin 3, vascular endothelial growth factor, and monocyte chemoattractant protein-1 (MCP-1) were measured in plasma samples. Coronary plaque characteristics were scored quantitatively in the form of coronary plaque risk score (CPRS). The estimated high-risk plaque characteristics for TLR were plaque rupture, plaque erosion, calcified nodule, lipid-rich plaque, thin-cap fibroatheroma, cholesterol crystals, macrophage infiltration, microchannels, calcification angle >90°, and microcalcifications. Each high-risk feature carries 1 point. Patients were defined as having a low CPRS (CPRS ≤3) or a high CPRS (CPRS ≥4). RESULTS: The primary outcome was TLR. TLR occurred in 6 (20%) patients within 15 months of PCI. High CPRS on OCT was directly correlated with TLR (P=0.029). In logistic regression analysis, CPRS was associated with TLR (odds ratio, 10.0; 95% confidence interval, 1.34-74.5). Serum MCP-1 level was significantly correlated with the CPRS (P=0.020). CONCLUSIONS: In patients with chronic coronary syndrome, CPRS may be a surrogate predictor of TLR. Serum MCP-1 may aid in the detection of high-risk coronary atherosclerosis.

Closed VSDを合併した右室二腔症の手術症例　　　　　　　　　　　　　　　
齋藤 翔太, 石坂 傑, 下野 裕依, 甲谷 太郎, 神谷 究, 阿部 慎司, 加藤 伸康, 永井 利幸, 若狭 哲, 安斉 俊久
日本成人先天性心疾患学会雑誌, 12, 1, 200, 200, (一社)日本成人先天性心疾患学会, Jan. 2023
Japanese

Validation of Echocardiographic Estimation of Right Atrial Pressure: Reconsideration of Guideline-Based Secondary Indices
Murayama Michito, Kaga Sanae, Onoda Airi, Okada Kazunori, Nakabachi Masahiro, Yokoyama Shinobu, Nishino Hisao, Aoyagi Hiroyuki, Tamaki Yoji, Motoi Ko, Ishizaka Suguru, Iwano Hiroyuki, Nagai Toshiyuki, Tsujino Ichizo, Anzai Toshihisa
Japanese Journal of Medical Ultrasound Technology, advpub, Japanese Society of Sonographers, 2023
Japanese, Purpose: Sonographic measurements of the inferior vena cava parameters are common noninvasive methods for estimating right atrial pressure. In intermediate cases in which the inferior vena cava parameters showed indeterminate value, the current guidelines of the American Society of Echocardiography recommended using secondary indices, which include restrictive right-sided diastolic filling pattern, the ratio of early-diastolic transtricuspid flow velocity to tricuspid annular velocity, and the hepatic venous systolic filling fraction. We aimed to clarify whether the above secondary indices improve the diagnostic ability of elevated right atrial pressure using inferior vena cava parameters and to test the incremental predictive value of right atrial area measurement.

Subjects and Methods: In 128 consecutive patients with various cardiac diseases referred for cardiac catheterization, the elevated right atrial pressure was defined as greater than or equal to 8 mmHg. Based on the inferior vena cava morphology, the estimated right atrial pressure was determined as 3, 8, and 15 mmHg (model 1). Additionally, the restrictive filling pattern, the ratio of early-diastolic transtricuspid flow velocity to tricuspid annular velocity, and the systolic filling fraction were evaluated to reclassify the intermediate value of 8 mmHg (model 2). The right atrial minimum and maximum area and volume were measured at ventricular end diastole and end systole, respectively, and the expansion indices were calculated.

Results: Elevated right atrial pressure was observed in 29 patients. Logistic regression analysis showed that estimated right atrial pressure based on the inferior vena cava indices and systolic filling fraction were significantly associated with elevated right atrial pressure (p＜0.05). Restrictive filling pattern was not observed in any of the patients, and the ratio of early-diastolic transtricuspid flow velocity to tricuspid annular velocity was not associated with elevated right atrial pressure. Right atrial morphological and functional parameters were significantly associated with elevated right atrial pressure (p＜0.05). Notably, the minimum right atrial area demonstrated the strongest association with right atrial pressure elevation (odds ratio adjusted for right ventricular systolic function: 10.64, p＜0.01). The predictive ability of model 2 was comparable to that of model 1 (global χ² value＝9 for model 1, 11 for model 2; p＝0.28). In contrast, incorporated with systolic filling fraction and minimal right atrial area as secondary indices, the predictive ability of the new model was improved compared to that of model 1 (global χ² value＝9 for model 1, 25 for the new model; p＜0.01).

Conclusion: Reclassification using guideline-recommended secondary indices failed to improve the predictive ability of elevated right atrial pressure. In contrast, a combination of systolic filling fraction and minimal right atrial area with inferior vena cava indices improved the predictive ability of elevated right atrial pressure.

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, 10 Dec. 2022, [International Magazine]
English, Scientific journal, 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.

Associations of right ventricular pulsatile load and cardiac power output to clinical outcomes in heart failure: Difference from systemic circulation.
Yasuyuki Chiba, Hiroyuki Iwano, Hiroyuki Aoyagi, Yoji Tamaki, Ko Motoi, Suguru Ishizaka, Michito Murayama, Shinobu Yokoyama, Masahiro Nakabachi, Hisao Nishino, Sanae Kaga, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Journal of cardiology, 81, 4, 404, 412, 08 Dec. 2022, [International Magazine]
English, Scientific journal, BACKGROUND: Although left ventricular (LV) cardiac power output (CPO) is a powerful prognostic indicator in heart failure (HF), the significance of right ventricular (RV) CPO is unknown. In contrast, RV pulsatile load is a key prognostic marker in HF. We investigated the impact of RV-CPO and pulsatile load on cardiac outcome and the prognostic performance of the combined systemic and pulmonary circulation parameters in HF. METHODS: Right heart catheterization and echocardiography were performed in 231 HF patients (62 ± 16 years, LV ejection fraction 42 ± 18 %). Invasive and noninvasive CPOs were calculated from mean systemic or pulmonary arterial pressure and cardiac output. LV-CPO was then normalized to LV mass (LV-P/M). Pulmonary arterial capacitance and the ratio of acceleration time to ejection time (AcT/ET) of RV outflow were used as parameters of RV pulsatile load. The primary endpoints, defined as a composite of cardiac death, HF hospitalization, ventricular arrythmia, and LVAD implantation after the examination, were recorded. RESULTS: Noninvasive CPOs were moderately correlated with invasive ones (LV: ρ = 0.787, RV: ρ = 0.568, and p < 0.001 for both). During a median follow-up period of 441 days, 57 cardiovascular events occurred. Lower LV-P/M and higher RV pulsatile load were associated with cardiovascular events; however, RV-CPO was not associated with the outcome. Echocardiographic LV-P/M and AcT/ET showed significant incremental prognostic value over the clinical parameters. CONCLUSIONS: RV pulsatile load assessed by AcT/ET may be a predictor of clinical events in HF patients. The combination of echocardiographic LV-P/M and AcT/ET could be a novel noninvasive prognostic indicator in HF patients.

Canagliflozin independently reduced plasma volume from conventional diuretics in patients with type 2 diabetes and chronic heart failure: a subanalysis of the CANDLE trial
Kazuki Shiina, Hirofumi Tomiyama, Atsushi Tanaka, Takumi Imai, Itaru Hisauchi, Isao Taguchi, Akira Sezai, Shigeru Toyoda, Kaoru Dohi, Haruo Kamiya, Keisuke Kida, Toshihisa Anzai, Taishiro Chikamori, Koichi Node, Masayoshi Ajioka, Junya Ako, Rie Amano, Mitsutoshi Asai, Kazuo Eguchi, Kenichi Eshima, Shinya Fujiki, Masashi Fujita, Shungo Hikoso, Shinya Hiramitsu, Satoshi Hoshide, Akihiko Hoshino, Yuki Ikeda, Yumi Ikehara, Takayuki Inomata, Teruo Inoue, Katsuhisa Ishii, Nobukazu Ishizaka, Masaaki Ito, Noriaki Iwahashi, Katsuomi Iwakura, Toshiaki Kadokami, Takahiro Kanbara, Yumiko Kanzaki, Ken Kashimura, Kazuo Kimura, Satoru Kishi, Shuichi Kitada, Masafumi Kitakaze, Akihiro Kiyosue, Kazuhisa Kodama, Takayuki Kojima, Takumi Kondo, Yoshiaki Kubota, Kenya Kusunose, Noritaka Machii, Kazuo Matsunaga, Yasuto Matsuo, Yashushi Matsuzawa, Takeshi Mikami, Toru Minamino, Toyoaki Murohara, Takahiro Nagai, Yasuko Nagano, Masashi Nagumo, Ikuko Nakamura, Katsunori Nakamura, Daisaku Nakatani, Mamoru Nanasato, Hiriyuki Naruse, Masami Nishino, Shinichi Niwano, Mitsutoshi Oguri, Nobuyuki Ohte, Masayoshi Oikawa, Takahiro Okumura, Masanori Okumura, Katsuya Onishi, Jun-ichi Oyama, Yukio Ozaki, Kan Saito, Tomohiro Sakamoto, Yasushi Sakata, Masashi Sakuma, Masataka Sata, Hisakuni Sekino, Michio Shimabukuro, Wataru Shimizu, Makoto Suzuki, Kunihiro Suzuki, Hiroyuki Takahama, Naohiko Takahashi, Yasuchika Takeishi, Shunsuke Tamaki, Akihiro Tanaka, Syuzo Tanimoto, Hiroki Teragawa, Tomoyuki Tobushi, Takafumi Toita, Kotaro Tokuda, Hiroyuki Tsutsui, Shinichiro Ueda, Hiroki Uehara, Masaaki Uematsu, Hirotaka Watada, Kazuyuki Yahagi, Takahisa Yamada, Hirotsugu Yamada, Tatsuya Yoshida, Akiomi Yoshihisa
Hypertension Research, Springer Science and Business Media LLC, 15 Nov. 2022
Scientific journal

Features and Outcomes of Histologically Proven Myocarditis With Fulminant Presentation
Koshiro Kanaoka, Kenji Onoue, Satoshi Terasaki, Tomoya Nakano, Michikazu Nakai, Yoko Sumita, Kinta Hatakeyama, Fumio Terasaki, Rika Kawakami, Yoshitaka Iwanaga, Yoshihiro Miyamoto, Yoshihiko Saito, Satoshi Yuda, Masaya Tanno, Toru Takahashi, Hisashi Yokoshiki, Masahiro Toba, Toshihisa Anzai, Toshiyuki Nagai, Takuma Sato, Takashi Takenaka, Seiji Yamazaki, Yuki Katagiri, Toshiharu Takeuchi, Kazuya Sugitatsu, Shigeo Kakinoki, Tomoaki Matsumoto, Kazushi Urasawa, Michinao Tan, Ichizo Tsujino, Mitsunori Kamigaki, Hirofumi Tomita, Kenji Hanada, Motoi Kushibiki, Akihiro Nakamura, Yoshihiro Morino, Takahito Nasu, Satoshi Yasuda, Hideaki Suzuki, Kaoru Iwabuchi, Kanako Tsuji, Shigeto Namiuchi, Tatsuya Komaru, Masahiro Yagi, Shoko Uematsu, Toshiaki Takahashi, Satoru Takeda, Toru Nakanishi, Masafumi Watanabe, Masahiro Wanezaki, Motoyuki Matsui, Shigeo Sugawara, Yasuchika Takeishi, Masayoshi Oikawa, Nobuo Komatsu, Satoshi Suzuki, Hiroshi Okamoto, Noriyuki Takeyasu, Daiki Akiyama, Yutaka Eki, Tsunekazu Kakuta, Tomoyo Sugiyama, Tomomi Koizumi, Koji Ueno, Kazuomi Kario, Mizuri Taki, Yuri Matsumoto, Takanori Yasu, Osamu Nishioka, Shigeto Naito, Makoto Murata, Shoichi Tange, Katsumi Kaneko, Makoto Muto, Hiroshi Inagaki, Shuichi Hasegawa, Eizo Tachibana, Wataru Atsumi, Masahiro Suzuki, Toshihiro Muramatsu, Yoshihiro Yamada, Isao Taguchi, Yoshiaki Fukuda, Akihiro Matsui, Junji Kanda, Koji Hozawa, Akihiko Matsumura, Wataru Shimizu, Takeshi Yamamoto, Issei Komuro, Masaru Hatano, Takanori Ikeda, Shunsuke Kiuchi, Taishiro Chikamori, Yasuyoshi Takei, Kyoko Soejima, Toshinori Minamishima, Hiroyuki Tanaka, Shigeo Shimizu, Masashi Kasao, Tadayuki Kadohira, Tohru Minamino, Kazunori Shimada, Hiroshi Iwata, Yukihiko Momiyama, Takashi Ashikaga, Toshihiro Nozato, Yasumasa Fujiwara, Kenji Inoue, Tetsuo Sasano, Junji Matsuda, Yasuhiro Ishii, Yuichi Ono, Kengo Tanabe, Yu Horiuchi, Toshiro Shinke, Yusuke Kodama, Masao Moroi, Yoshiyuki Yazaki, Taisuke Mizumura, Hiroshi Ohta, Yoshihiro Akashi, Nozomi Kotoku, Yuji Ikari, Mitsunori Maruyama, Yasuhiro Sato, Koichi Tamura, Masaaki Konishi, Hiroshi Suzuki, Mio Ebato, Kazuki Fukui, Kazuhiko Yumoto, Takamasa Iwasawa, Takeshi Kashimura, Kazuyoshi Takahashi, Yoshinobu Okada, Bunji Kaku, Kazuo Usuda, Michiro Maruyama, Tomoki Kameyama, Toshinori Higashikata, Akihiko Hodatsu, Kazuo Osato, Yoji Nagata, Koji Maeno, Kazuo Satake, Takao Sawanobori, Noboru Watanabe, Koichiro Kuwahara, Hirohiko Motoki, Hiroshi Kitabayashi, Kyuhachi Otagiri, Tsunesuke Kono, Daisuke Yamagishi, Yoshikazu Yazaki, Toshiyuki Noda, Itsuro Morishima, Naoki Watanabe, Shinichiro Tanaka, Tomoya Onodera, Ryuzo Nawada, Akinori Watanabe, Masaki Matsunaga, Satoru Suwa, Hiroshi Sakamoto, Hiroki Sakamoto, Takeshi Aoyama, Norio Kanamori, Masahiro Muto, Yuichiro Maekawa, Hayato Ohtani, Yukio Ozaki, Kenshin Naruse, Kenji Takemoto, Haruo Kamiya, Takeshi Suzuki, Yasushi Tomita, Susumu Suzuki, Ryosuke Kametani, Hidekazu Aoyama, Hiroyuki Osanai, Ken Harada, Kenji Kada, Tomoaki Saeki, Koichi Kobayashi, Yasuhiro Ogawa, Akihiro Terasawa, Masanori Shinoda, Mitsutoshi Oguri, Kiyokazu Shimizu, Akinori Sawamura, Atsushi Sugiura, Kosuke Hattori, Shinji Mokuno, Kazuhisa Kondo, Kaoru Dohi, Keishi Moriwaki, Atsunobu Kasai, Tetsuya Nakakuki, Kazuaki Kaitani, Toshikazu Jinnai, Takashi Yamamoto, Hiroyuki Kurata, Atsuyuki Wada, Masaharu Akao, Yasuhiro Hamatani, Kazuya Ishibashi, Yoshiki Akakabe, Yasuhide Asaumi, Hideo Matama, Yasushi Sakata, Hidetaka Kioka, Hiroshi Takaishi, Yoshitaka Iwanaga, Toru Takase, Mitsuo Matsuda, Fumi Sato, Shinji Hasegawa, Kenichi Ishigami, Minoru Ichikawa, Takashi Takagi, Moriaki Inoko, Masaaki Hoshiga, Shuichi Fujita, Yoshihiro Takeda, Takahiko Kawarabayashi, Hideyuki Takaoka, Kenji Nakajima, Tadashi Yuguchi, Tatsuya Kawasaki, Yukinori Shinoda, Yukihito Sato, Masaharu Ishihara, Yuki Matsumoto, Hiroya Kawai, Tomofumi Takaya, Kouki Matsuo, Toshiaki Mano, Kenichi Hirata, Eriko Hisamatsu, Nobutaka Inoue, Koichi Tamita, Naoki Mukohara, Hisashi Shimoyama, Toru Miyajima, Toshihiro Tamura, Yodo Tamaki, Megumi Suzuki, Ryoji Yokota, Manabu Horii, Kazuo Yamanaka, Hiroyuki Kawata, Yukihiro Hashimoto, Yasuki Nakada, Hitoshi Nakagawa, Tomoya Ueda, Taku Nishida, Ayako Seno, Makoto Watanabe, Takashi Akasaka, Takashi Tanimoto, Mamoru Toyofuku, Kazuhiro Yamamoto, Yoshiharu Kinugasa, Masayuki Hirai, Hiroshi Nasu, Kinya Shirota, Tsuyoshi Oda, Takefumi Oka, Kazushige Kadota, Masanobu Ohya, Hiroshi Ito, Kazufumi Nakamura, Soichiro Ogura, Soichiro Fuke, Shiro Uemura, Hiromi Matsubara, Atsuyuki Watanabe, Nobuyuki Morishima, Yasuki Kihara, Takayuki Hidaka, Hironori Ueda, Yujiro Ono, Yuji Muraoka, Miyo Hatanari, Yoshinori Miyamoto, Keigo Dote, Masaya Kato, Masafumi Yano, Mamoru Mochizuki, Yasuhiro Ikeda, Hiroyuki Fujinaga, Shinobu Hosokawa, Masataka Sata, Koji Yamaguchi, Naoko Aki, Tetsuo Minamino, Yuichi Miyake, Yuichiro Takagi, Masayuki Doi, Yoshio Taketani, Hideki Okayama, Tatsuya Shigematsu, Akinori Higaki, Osamu Yamaguchi, Shinji Inaba, Shuntaro Ikeda, Kazuya Kawai, Hiroaki Kitaoka, Toru Kubo, Kenji Ando, Kaoru Inui, Yoshihiro Fukumoto, Kensuke Hori, Takehiro Homma, Tomohiro Kawasaki, Masahiro Mohri, Masaki Fujiwara, Hiroyuki Tsutsui, Tomomi Ide, Shin-Ichiro Miura, Takashi Kuwano, Hideki Shimomura, Toshiaki Kadokami, Masanao Taba, Katsuhiro Kondou, Toru Kubota, Daisuke Nagatomo, Yasushi Mukai, Ryuichi Matsukawa, Hideki Tashiro, Mitsuhiro Shimomura, Koji Maemura, Hiroaki Kawano, Koji Oku, Toshihiko Yamasa, Yoshihisa Kizaki, Tomohiro Sakamoto, Yudai Tamura, Teruhiko Ito, Kazuteru Fujimoto, Kenichi Tsujita, Seiji Takashio, Hirofumi Kurokawa, Naohiko Takahashi, Shotaro Saito, Masaya Arikawa, Yoshisato Shibata, Kensaku Nishihira, Toshihiro Tsuruda, Masahiro Sonoda, Nobuhiko Atsuchi, Mitsuru Ohishi, Koji Higuchi, Masaaki Miyata, Naoya Oketani, Yoshinori Akimoto, Tomohiro Asahi, Minoru Wake
Circulation, 146, 19, 1425, 1433, Ovid Technologies (Wolters Kluwer Health), 08 Nov. 2022, [Peer-reviewed]
Scientific journal, Background:

Fulminant myocarditis presentation (FMP) is a rare and severe presentation of myocarditis. The natural history of FMP and its clinical features associated with poor outcomes are incompletely understood because there is a lack of generalizable evidence.

Methods:

This multicenter retrospective cohort study included patients hospitalized with histologically proven myocarditis who underwent catecholamine or mechanical support from 235 cardiovascular training hospitals across Japan between April 2012 and March 2017. Clinical features and the prognostic predictors of death or heart transplantation within 90 days on the basis of clinical and pathologic findings were determined using the Kaplan-Meier method, log-rank test, and Cox regression analysis.

Results:

This study included 344 patients with histologically proven FMP (median age, 54 years; 40% female). The median follow-up was 600 days (interquartile range, 36 to 1599 days) and the cumulative risk of death or heart transplantation at 90 days was 29% (n=98). Results from multivariable Cox regression analysis showed that older age, nonsinus rhythm, low left ventricular wall motion (<40%) on admission, and ventricular tachycardia or fibrillation on admission day were associated with worse 90-day survival. Severe histologic damage (damaged cardiomyocytes comprising ≥50% of the total cardiomyocytes) was associated with a worse 90-day prognosis in patients with lymphocytic myocarditis.

Conclusions:

The results from analyses of data from this multicenter registry demonstrated that patients with FMP are at a higher risk of death or heart transplantation in real-world settings. These observations inform which clinical and pathologic findings may be useful for prognostication in FMP.

Registration:

URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000039763.

Liver stiffness assessed by magnetic resonance elastography predicts clinical outcomes in patients with heart failure and without chronic liver disease.
Atsushi Tada, Toshiyuki Nagai, Yoshiya Kato, Kazunori Omote, Noriko Oyama-Manabe, Satonori Tsuneta, Yusuke Kudo, Mutsumi Nishida, Michikazu Nakai, Yuki Takahashi, Kohei Saiin, Seiichiro Naito, Yuta Kobayashi, Sakae Takenaka, Yoshifumi Mizuguchi, Kiwamu Kamiya, Takao Konishi, Takuma Sato, Kohsuke Kudo, Toshihisa Anzai
European radiology, 33, 3, 2062, 2074, 03 Nov. 2022, [International Magazine]
English, Scientific journal, OBJECTIVES: Evaluation of liver stiffness (LS) by magnetic resonance elastography (MRE) is useful for estimating right atrial pressure (RAP) in patients with heart failure (HF). However, its prognostic implications are unclear. We sought to investigate whether LS measured by MRE (LS-MRE) could predict clinical outcomes in patients with HF. METHODS: We prospectively examined 207 consecutive HF patients between April 2018 and May 2021 after excluding those with organic liver disease. All patients underwent 3.0-T MRE. The primary outcome of interest was the composite of all-cause death and hospitalisation for HF. RESULTS: During a median follow-up period of 720 (interquartile range [IQR] 434-1013) days, the primary outcome occurred in 44 patients (21%), including 15 (7%) all-cause deaths and 29 (14%) hospitalisations for HF. The patients were divided into two groups according to median LS-MRE of 2.54 (IQR 2.34-2.82) kPa. Patients with higher LS-MRE showed a higher incidence of the primary outcome compared to those with lower LS-MRE (p < 0.001). Multivariable Cox regression analyses revealed that LS-MRE value was independently associated with the risk of adverse events (hazard ratio 2.49, 95% confidence interval 1.46-4.24). In multivariable linear regression, RAP showed a stronger correlation with LS-MRE (β coefficient = 0.31, p < 0.001) compared to markers related to liver fibrosis. CONCLUSIONS: In patients without chronic liver disease and presenting with HF, elevated LS-MRE was independently associated with worse clinical outcomes. Elevated LS-MRE may be useful for risk stratification in patients with HF and without chronic liver disease. KEY POINTS: • Magnetic resonance elastography (MRE) is an emerging non-invasive imaging technique for evaluating liver stiffness (LS) which can estimate right atrial pressure. • Elevated LS-MRE, which mainly reflects liver congestion, was independently associated with worse clinical outcomes in patients with heart failure. • The assessment of LS-MRE would be useful for stratifying the risk of adverse events in heart failure patients without chronic liver disease.

抗ミトコンドリアM2抗体陽性筋炎17例の臨床的特徴
長井 梓, 永井 利幸, 矢口 裕章, 藤井 信太朗, 上床 尚, 白井 慎一, 岩田 育子, 松島 理明, 堀内 一宏, 浦 茂久, 安斉 俊久, 矢部 一郎
神経治療学, 39, 6, S263, S263, (一社)日本神経治療学会, Oct. 2022
Japanese

日本人心臓サルコイドーシス患者におけるAHA/ACC/HRSガイドライン植込型除細動器適応の外的妥当性　　　　　　　　　　　　　　　
竹中 秀, 小林 雄太, 永井 利幸, 加藤 喜哉, 小森山 弘和, 永野 伸卓, 神谷 究, 小西 崇夫, 佐藤 琢真, 表 和徳, 多田 篤司, 水口 賢史, 草野 研吾, 植田 初江, 安斉 俊久
日本サルコイドーシス/肉芽腫性疾患学会雑誌, 42, サプリメント号, 64, 64, 日本サルコイドーシス, Oct. 2022
Japanese

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, 23 Sep. 2022, [International Magazine]
English, Scientific journal, 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. 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 post-translational modification of SK channels.

Determinants of exercise capacity in patients with heart failure without left ventricular hypertrophy.
Suguru Ishizaka, Hiroyuki Iwano, Shingo Tsujinaga, Michito Murayama, Satonori Tsuneta, Hiroyuki Aoyagi, Yoji Tamaki, Ko Motoi, Yasuyuki Chiba, Asuka Tanemura, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Kazunori Okada, Brett A Meyers, Pavlos P Vlachos, Takuma Sato, Kiwamu Kamiya, Masaya Watanabe, Sanae Kaga, Toshiyuki Nagai, Noriko Oyama-Manabe, Toshihisa Anzai
Journal of cardiology, 81, 1, 33, 41, 16 Sep. 2022, [International Magazine]
English, Scientific journal, BACKGROUND: Determinants of exercise intolerance in a phenotype of heart failure with preserved ejection fraction (HFpEF) with normal left ventricular (LV) structure have not been fully elucidated. METHODS: Cardiopulmonary exercise testing and exercise-stress echocardiography were performed in 44 HFpEF patients without LV hypertrophy. Exercise capacity was determined by peak oxygen consumption (peak VO2). Doppler-derived cardiac output (CO), transmitral E velocity, systolic (LV-s') and early diastolic mitral annular velocities (e'), systolic pulmonary artery (PA) pressure (SPAP), tricuspid annular plane systolic excursion (TAPSE), and peak systolic right ventricular (RV) free wall velocity (RV-s') were measured at rest and exercise. E/e' and TAPSE/SPAP were used as an LV filling pressure parameter and RV-PA coupling, respectively. RESULTS: During exercise, CO, LV-s', RV-s', e', and SPAP were significantly increased (p < 0.05 for all), whereas E/e' remained unchanged and TAPSE/SPAP was significantly reduced (p < 0.001). SPAP was higher and TAPSE/SPAP was lower at peak exercise in patients showing lower-half peak VO2. In univariable analyses, LV-s' (R = 0.35, p = 0.022), SPAP (R = -0.40, p = 0.008), RV-s' (R = 0.47, p = 0.002), and TAPSE/SPAP (R = 0.42, p = 0.005) were significantly correlated with peak VO2. In multivariable analyses, not only SPAP, but also TAPSE/SPAP independently determined peak VO2 even after the adjustment for clinically relevant parameters. CONCLUSIONS: In HFpEF patients without LV hypertrophy, altered RV-PA coupling by exercise could be associated with exercise intolerance, which might not be caused by elevated LV filling pressure.

末期心不全患者の難治性不整脈に対するICD治療機能停止(deactivation)の検討を多職種で行った一例　　　　　　　　　　　　　　　
甲谷 次郎, 佐藤 琢真, 立田 大志郎, 西野 広太郎, 小林 雄太, 成田 尚, 敦賀 健吉, 青陽 千果, 池田 陽子, 小島 尚子, 古山 勇気, 小野田 紘子, 加藤 美香, 永井 利幸, 安斉 俊久
日本心臓病学会学術集会抄録, 70回, C, 3, (一社)日本心臓病学会, Sep. 2022
Japanese

COVID-19で入院加療中に冠攣縮性狭心症を併発した褐色細胞腫の一例　　　　　　　　　　　　　　　
高橋 昌寛, 佐藤 琢真, 立田 大志郎, 甲谷 次郎, 西野 広太郎, 小林 雄太, 小西 崇夫, 永井 利幸, 安斉 俊久
日本心臓病学会学術集会抄録, 70回, C, 5, (一社)日本心臓病学会, Sep. 2022
Japanese

Clinical features of anti-mitochondrial M2 antibody-positive myositis: case series of 17 patients.
Azusa Nagai, Toshiyuki Nagai, Hiroaki Yaguchi, Shintaro Fujii, Hisashi Uwatoko, Shinichi Shirai, Kazuhiro Horiuchi, Ikuko Iwata, Masaaki Matsushima, Shigehisa Ura, Toshihisa Anzai, Ichiro Yabe
Journal of the neurological sciences, 442, 120391, 120391, 28 Aug. 2022, [International Magazine]
English, Scientific journal, OBJECTIVE: In 2012, a large number of myositis cases with anti-mitochondrial M2 (AMA-M2) antibody, which had well been known as the serological hallmark for primary biliary cholangitis (PBC), were reported in Japan. Recently, some case series from Japan, France, America, China and India have shown that approximately 2.5% to 19.5% of patients with myositis have AMA-M2 antibody. The objective of this study was to clarify the prevalence, clinical features, treatment outcome, and severity determinants of AMA-M2 positive myositis. METHODS: This study was a multicenter observational study. We enrolled patients who were diagnosed with myositis during a ten-year period between 2012 and 2021. RESULTS: Of the total of 185 patients with inflammatory myopathy, 17 patients were positive for AMA-M2 antibody. The typical symptoms were weakness mainly involving paravertebral muscles, weight loss, respiratory failure, and cardiac complications. Thirteen of the 17 patients had cardiac complications. A strong correlation was found between respiratory failure and modified Rankin Scale (mRS) score. A strong correlation was also found between respiratory failure and body weight, indicating that weight loss can be an indicator of potential progression of respiratory failure. Six of the 17 patients were complicated by malignancy. CONCLUSIONS: This study showed significant correlations between % vital capacity (VC), body mass index (BMI), and mRS score in patients with AMA-M2-positive myositis. Immunotherapy often improved CK level and respiratory dysfunction. We therefore propose that %VC and BMI should be monitored as disease indicators in treatment of AMA-M2-positive myositis.

Usefulness of Dual Gate Doppler in Assessing the Time Interval Between Pulmonary Venous and Transmitral Flows During Atrial Contraction
Okada Kazunori, Okada Yuka, Murayama Michito, Kaga Sanae, Masauzi Nobuo, Nishino Hisao, Yokoyama Shinobu, Nakabachi Masahiro, Nishida Mutsumi, Motoi Ko, Ishizaka Suguru, Chiba Yasuyuki, Tsujinaga Shingo, Iwano Hiroyuki, Anzai Toshihisa
Japanese Journal of Medical Ultrasound Technology, 47, 4, 353, 362, Japanese Society of Sonographers, 01 Aug. 2022
Japanese, Purpose: The difference in duration between pulmonary venous (PV) atrial systolic reversal wave (PVA) and atrial systolic wave (A) of transmitral flow (ΔA_dur) reflects the late-diastolic left ventricular (LV) operating stiffness and has a limitation on reproducibility. Using the Dual Gate Doppler technique, simultaneous recording of PV and transmitral flows can be obtained, which may contribute to improving the accuracy and reproducibility of ΔA_dur measurements.

Methods and Results: We examined 80 patients who underwent echocardiography using Dual Gate Doppler recording. Using the conventional Doppler recording, we measured the difference in duration between the PVA and transmitral A-wave (S-ΔA_dur). Additionally, the ratio of the time–velocity integral (TVI) of the PVA to that of the whole PV flow (F_PVA) and the ratio of the TVI in transmitral A-wave of the whole transmitral flow (F_A) were calculated, and F_PVA/F_A was obtained as an index of LV operating stiffness. From the Dual Gate Doppler recording of PV and transmitral flows, we measured ΔA_dur (D-ΔA_dur) and time from the end of transmitral A-wave to the end of PVA (D-ΔA_end).

Results: Each of S-ΔA_dur, D-ΔA_dur, and D-ΔA_end significantly correlated with F_PVA/F_A (r＝0.50, 0.51, and 0.71, respectively), and the correlation between F_PVA/F_A and D-ΔA_end was significantly greater than that between F_PVA/F_A and S-ΔA_dur and between F_PVA/F_A and D-ΔA_dur (p＜0.001 for both). The intraclass correlation coefficients for the inter- and intra-observer comparisons were excellent for D-ΔA_end, adequate for D-ΔA_dur, and fair for S-ΔA_dur.

Conclusion: Dual Gate Doppler-derived D-ΔA_end has higher reproducibility and usefulness for assessing late-diastolic LV operating stiffness than the conventional Doppler-derived S-ΔA_dur.

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, Aug. 2022, [International Magazine]
English, Scientific journal, 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.

Usefulness of the pulmonary venous flow waveform for assessing left atrial stiffness
Takehiro Abe, Kazunori Okada, Michito Murayama, Sanae Kaga, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Hiroyuki Aoyagi, Yoji Tamaki, Ko Motoi, Yasuyuki Chiba, Suguru Ishizaka, Shingo Tsujinaga, Hiroyuki Iwano, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
The International Journal of Cardiovascular Imaging, Springer Science and Business Media LLC, 16 Jul. 2022
Scientific journal

MitraClip実施後にたこつぼ症候群を呈した1例　　　　　　　　　　　　　　　
甲谷 次郎, 神谷 究, 立田 大志郎, 西野 広太郎, 高橋 勇樹, 斎院 康平, 内藤 正一郎, 竹中 秀, 多田 篤司, 水口 賢史, 石坂 傑, 小林 雄太, 佐藤 琢真, 永井 利幸, 安斉 俊久
日本心血管インターベンション治療学会抄録集, 30回, [YIA4, 2], (一社)日本心血管インターベンション治療学会, Jul. 2022
English

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).
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 : official journal of the Japanese Circulation Society, 86, 7, 1092, 1101, 24 Jun. 2022, [Domestic magazines]
English, Scientific journal, BACKGROUND: Dilated cardiomyopathy (DCM) associated with inflammation is diagnosed by endomyocardial biopsy; patients with this have a poorer prognosis than patients without inflammation. To date, standard diagnostic criteria have not been established.Methods and Results: This study analyzed clinical records and endomyocardial biopsy samples of 261 patients with DCM (201 males, median left ventricular ejection fraction; 28%) from 8 institutions in a multicenter retrospective study. Based on the European Society of Cardiology criteria and CD3 (T-lymphocytes) and CD68 (macrophages) immunohistochemistry, 48% of patients were categorized as having inflammatory DCM. For risk-stratification, we divided patients into 3 groups using Akaike Information Criterion/log-rank tests, which can determine multiple cut-off points: CD3+-Low, <13/mm2(n=178, 68%); CD3+-Moderate, 13-24/mm2(n=58, 22%); and CD3+-High, ≥24/mm2(n=25, 10%). The survival curves for cardiac death or left ventricular assist device implantation differed significantly among the 3 groups (10-year survival rates: CD3+-Low: 83.4%; CD3+-Moderate: 68.4%; CD3+-High: 21.1%; Log-rank P<0.001). Multivariate Cox analysis revealed CD3+count as a potent independent predictive factor for survival (fully adjusted hazard ratio: CD3+-High: 5.70, P<0.001; CD3+-Moderate: 2.64, P<0.01). CD3+-High was also associated with poor left ventricular functional and morphological recovery at short-term follow up. CONCLUSIONS: Myocardial CD3+T-lymphocyte infiltration has a significant prognostic impact in DCM and a 3-tiered risk-stratification model could be helpful to refine patient categorization.

Cogan Syndrome with Aortic Regurgitation and Multiple Vasculopathy.
Kohei Saiin, Takao Konishi, Keita Ninagawa, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 61, 12, 1921, 1922, 15 Jun. 2022, [Domestic magazines]
English, Scientific journal

Luseogliflozin preserves the pancreatic beta-cell mass and function in db/db mice by improving mitochondrial function.
Yuki Yamauchi, Akinobu Nakamura, Takashi Yokota, Kiyohiko Takahashi, Shinichiro Kawata, Kazuhisa Tsuchida, Kazuno Omori, Hiroshi Nomoto, Hiraku Kameda, Kyu Yong Cho, Toshihisa Anzai, Shinya Tanaka, Yasuo Terauchi, Hideaki Miyoshi, Tatsuya Atsumi
Scientific reports, 12, 1, 9740, 9740, 13 Jun. 2022, [International Magazine]
English, Scientific journal, We aimed to determine the mechanism by which the sodium glucose co-transporter 2 inhibitor, luseogliflozin, preserves pancreatic beta-cell mass and function in db/db mice. Six-week-old db/db mice were fed to standard chow or standard chow containing 0.01% luseogliflozin. After 4 weeks, DNA microarray analysis, real-time PCR analysis, and measurement of mitochondrial respiratory capacity and reactive oxygen species (ROS) generation were performed using isolated islets. Immunohistochemistry and electron microscopic analysis were performed using pancreatic tissues. Metabolites extracted from the islets were measured by capillary electrophoresis mass spectrometry. The expression of genes involved in the tricarboxylic acid (TCA) cycle and electron transport chain was upregulated by luseogliflozin. Luseogliflozin improved the mitochondrial complex II-linked oxidative phosphorylation capacity and reduced ROS generation. Mitochondrial morphology was normally maintained by luseogliflozin. Luseogliflozin increased NK6 homeobox 1 (NKX6.1) expression and TCA cycle metabolites. Relief of glucotoxicity by luseogliflozin may involve lower mitochondrial ROS generation and an improvement in complex II-linked mitochondrial respiration. Reducing ROS generation through preventing complex II damage likely increases NKX6.1 expression and ameliorate glucose metabolism in the TCA cycle, contributing to the protection of pancreatic beta-cells. Protection of complex II in pancreatic beta-cells represents a novel therapeutic target for type 2 diabetes.

Long-term preservation of functional capacity and quality of life in advanced heart failure patients with bridge to transplant therapy: A report from Japanese nationwide multicenter registry.
Takuma Sato, Yuta Kobayashi, Toshiyuki Nagai, Takeshi Nakatani, Jon Kobashigawa, Yoshikatsu Saiki, Minoru Ono, Satoru Wakasa, Toshihisa Anzai
International journal of cardiology, 356, 66, 72, 01 Jun. 2022, [International Magazine]
English, Scientific journal, BACKGROUND: Under the revised heart allocation system in the United States, bridge to transplant (BTT) patients with left ventricular assist device (LVAD) have a longer waitlist period, as they are now lowly prioritized. However, little is known regarding the long-term trajectory of functional capacity (FC) and health-related quality of life (HR-QOL) among BTT-LVAD patients. METHODS: We retrospectively analyzed 442 consecutive patients with BTT-LVAD between April 2013 and May 2019 from a Japanese nationwide registry. FC (New York Heart Association [NYHA] functional class, peak oxygen uptake [VO2], and 6-min walk test [6MWT]) and HR-QOL (European Quality of Life [EQ-5D index] and Visual Analogue Scale [EQ-VAS]) were assessed at baseline and for up to 60 months after LVAD implantation. RESULTS: During the follow-up period of 30 months (IQR 18-42 months), 100 (22.6%) patients underwent transplantation, 37 (8.3%) died, and 14 (3.1%) underwent explantation for recovery. Mean peak VO2, 6MWT distance, EQ-5D index, and EQ-VAS significantly improved 3 months after LVAD implantation (p = 0.0012, p = 0.0037, p < 0.001, p < 0.001, respectively). Furthermore, these improvements were sustained for up to 60 months following LVAD implantation. Major adverse events including device failure, infection, stroke, and bleeding, which occurred within the first 3 months after LVAD implantation may have not affected FC or HR-QOL for up to 60 months (p = 0.15, p = 0.22, respectively). CONCLUSIONS: BTT patients showed long-term preservation of FC and HR-QOL, suggesting that BTT remains an option despite the long waiting time to HTx.

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, 31 May 2022, [International Magazine]
English, Scientific journal, 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.

Two cases showing alterations of the order of tricuspid and mitral valve opening during loading manipulations: a new approach for quick assessment of stress-induced left ventricular filling pressure elevation.
Michito Murayama, Hiroyuki Iwano, Ko Motoi, Suguru Ishizaka, Shingo Tsujinaga, Toshiyuki Nagai, Toshihisa Anzai
Journal of medical ultrasonics (2001), 49, 3, 489, 491, 30 May 2022, [Domestic magazines]
English, Scientific journal

Visual echocardiographic scoring system of the left ventricular filling pressure and outcomes of heart failure with preserved ejection fraction.
Michito Murayama, Hiroyuki Iwano, Masaru Obokata, Tomonari Harada, Kazunori Omote, Kazuki Kagami, Shingo Tsujinaga, Yasuyuki Chiba, Suguru Ishizaka, Ko Motoi, Yoji Tamaki, Hiroyuki Aoyagi, Masahiro Nakabachi, Hisao Nishino, Shinobu Yokoyama, Asuka Tanemura, Kazunori Okada, Sanae Kaga, Mutsumi Nishida, Toshiyuki Nagai, Masahiko Kurabayashi, Toshihisa Anzai
European heart journal. Cardiovascular Imaging, 23, 5, 616, 626, 18 Apr. 2022, [International Magazine]
English, Scientific journal, AIMS: Elevated left ventricular filling pressure (LVFP) is a powerful indicator of worsening clinical outcomes in heart failure with preserved ejection fraction (HFpEF); however, detection of elevated LVFP is often challenging. This study aimed to determine the association between the newly proposed echocardiographic LVFP parameter, visually assessed time difference between the mitral valve and tricuspid valve opening (VMT) score, and clinical outcomes of HFpEF. METHODS AND RESULTS: We retrospectively investigated 310 well-differentiated HFpEF patients in stable conditions. VMT was scored from 0 to 3 using two-dimensional echocardiographic images, and VMT ≥2 was regarded as a sign of elevated LVFP. The primary endpoint was a composite of cardiac death or heart failure hospitalization during the 2 years after the echocardiographic examination. In all patients, Kaplan-Meier curves showed that VMT ≥2 (n = 54) was associated with worse outcomes than the VMT ≤1 group (n = 256) (P < 0.001). Furthermore, VMT ≥2 was associated with worse outcomes when tested in 100 HFpEF patients with atrial fibrillation (AF) (P = 0.026). In the adjusted model, VMT ≥2 was independently associated with the primary outcome (hazard ratio 2.60, 95% confidence interval 1.46-4.61; P = 0.001). Additionally, VMT scoring provided an incremental prognostic value over clinically relevant variables and diastolic function grading (χ2 10.8-16.3, P = 0.035). CONCLUSIONS: In patients with HFpEF, the VMT score was independently and incrementally associated with adverse clinical outcomes. Moreover, it could also predict clinical outcomes in HFpEF patients with AF.

SGLT2阻害薬はミトコンドリア機能の改善を介し膵β細胞量・機能を保護する
山内 裕貴, 中村 昭伸, 横田 卓, 高橋 清彦, 川田 晋一朗, 土田 和久, 大森 一乃, 野本 博司, 亀田 啓, 曹 圭龍, 安斉 俊久, 田中 伸哉, 寺内 康夫, 三好 秀明, 渥美 達也
日本内分泌学会雑誌, 98, 1, 361, 361, (一社)日本内分泌学会, Apr. 2022
Japanese

Difference in left atrial myocardial dynamics during reservoir phase between hypertrophic cardiomyopathy and hypertensive heart determined using three-dimensional speckle tracking echocardiography
Yusuke Yanagi, Kazunori Okada, Sanae Kaga, Taisei Mikami, Miho Aiba, Nobuo Masauzi, Michito Murayama, Asuka Tanemura, Shinobu Yokoyama, Hisao Nishino, Masahiro Nakabachi, Yoji Tamaki, Hiroyuki Aoyagi, Ko Motoi, Suguru Ishizaka, Yasuyuki Chiba, Shingo Tsujinaga, Hiroyuki Iwano, Toshihisa Anzai
INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING, Apr. 2022
English, Scientific journal

Prognostic value of an echocardiographic index reflecting right ventricular operating stiffness in patients with heart failure.
Ryosuke Fujisawa, Kazunori Okada, Sanae Kaga, Michito Murayama, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Asuka Tanemura, Nobuo Masauzi, Ko Motoi, Suguru Ishizaka, Yasuyuki Chiba, Shingo Tsujinaga, Hiroyuki Iwano, Toshihisa Anzai
Heart and vessels, 37, 4, 583, 592, Apr. 2022, [Domestic magazines]
English, Scientific journal, PURPOSE: We recently reported a noninvasive method for the assessment of right ventricular (RV) operating stiffness that is obtained by dividing the atrial-systolic descent of the pulmonary artery-RV pressure gradient (PRPGDAC) derived from the pulmonary regurgitant velocity by the tricuspid annular plane movement during atrial contraction (TAPMAC). Here, we investigated whether this parameter of RV operating stiffness, PRPGDAC/TAPMAC, is useful for predicting the prognosis of patients with heart failure (HF). METHODS: We retrospectively included 127 hospitalized patients with HF who underwent an echocardiographic examination immediately pre-discharge. The PRPGDAC/TAPMAC was measured in addition to standard echocardiographic parameters. Patients were followed until 2 years post-discharge. The endpoint was the composite of cardiac death, readmission for acute decompensation, and increased diuretic dose due to worsening HF. RESULTS: 58 patients (46%) experienced the endpoint during follow-up. Univariable and multivariable Cox regression analyses demonstrated that the PRPGDAC/TAPMAC was associated with the endpoint. In a Kaplan-Meier analysis, the event rate of the greater PRPGDAC/TAPMAC group was significantly higher than that of the lesser PRPGDAC/TAPMAC group. In a sequential Cox analysis for predicting the endpoint's occurrence, the addition of PRPGDAC/TAPMAC to the model including age, sex, NYHA functional classification, brain natriuretic peptide level, and several echocardiographic parameters including tricuspid annular plane systolic excursion significantly improved the predictive power for prognosis. CONCLUSION: A completely noninvasive index of RV operating stiffness, PRPGDAC/TAPMAC, was useful for predicting prognoses in patients with HF, and it showed an incremental prognostic value over RV systolic function.

Right atrial pressure represents cumulative cardiac burden in heart failure with preserved ejection fraction.
Reika Nagata, Tomonari Harada, Kazunori Omote, Hiroyuki Iwano, Kotaro Yoshida, Toshimitsu Kato, Koji Kurosawa, Toshiyuki Nagai, Toshihisa Anzai, Masaru Obokata
ESC heart failure, 9, 2, 1454, 1462, Apr. 2022, [International Magazine]
English, Scientific journal, AIMS: Right-sided filling pressure is elevated in some patients with heart failure (HF) and preserved ejection fraction (HFpEF). We hypothesized that right atrial pressure (RAP) would represent the cumulative burden of abnormalities in the left heart, pulmonary vasculature, and the right heart. METHODS AND RESULTS: Echocardiography was performed in 399 patients with HFpEF. RAP was estimated from inferior vena cava morphology and its respiratory change [estimated right atrial pressure (eRAP)], and patients were divided according to eRAP (3 or ≥8 mmHg). Patients with higher eRAP displayed more severe abnormalities in LV diastolic function as well as right heart structure and function than those with normal eRAP. Cardiac deaths or HF hospitalization occurred in 84 patients over a median follow-up of 19.0 months (interquartile range 6.7-36.9). The presence of higher eRAP was independently associated with an increased risk of the composite outcome (adjusted hazard ratio 2.20 vs. normal eRAP group, 95% confidence interval 1.34-3.62, P = 0.002). Kaplan-Meier curves separating the patients into four groups based on eRAP and E/e' ratio showed that event-free survival varied among the groups, providing an incremental prognostic value of eRAP over E/e' ratio. The classification and regression tree analysis demonstrated that eRAP was the strongest predictor of the outcome followed by right ventricular dimension, E/e' ratio, and estimated right ventricular systolic pressure, stratifying the patients into four risk groups (incident rate 8.8-72.2%). CONCLUSIONS: These data may provide new insights into the prognostic role of RAP in the complex pathophysiology of HFpEF and suggest the utility of eRAP for the risk stratification in patients with HFpEF.

Rapid Publication and Announcement of the 2022 JCS Meeting Activities.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 86, 4, 589, 590, 25 Mar. 2022, [Domestic magazines]
English, Scientific journal

Impact of Tweeting Summaries by the Japanese Circulation Society Official Account on Article Viewership - Pilot Trial.
Atsushi Mizuno, Kenya Kusunose, Takuya Kishi, Jeffrey Rewley, Chisa Matsumoto, Yuki Sahashi, Mari Ishida, Shoji Sanada, Memori Fukuda, Tadafumi Sugimoto, Miki Hirano, Daisuke Yoneoka, Masataka Sata, Toshihisa Anzai, Koichi Node
Circulation journal : official journal of the Japanese Circulation Society, 86, 4, 715, 720, 25 Mar. 2022, [Domestic magazines]
English, Scientific journal, BACKGROUND: The impact of promotional tweets from the official journal account (forCirculation JournalandCirculation Reports) on article viewership has not been thoroughly evaluated.Methods and Results:We retrospectively collected journal viewership data forCirculation JournalandCirculation Reportsfrom March 2021 to August 2021. We compared viewership between articles with (n=15) and without (n=250) tweets. After 1 : 4 propensity score matching (15 tweeted articles and 60 non-tweeted matched controls), journal viewership metrics within 7 days of the tweeting date (and the hypothetical tweeting date), was larger in tweeted articles than non-tweeted articles (median [interquartile range] Abstract page views 89 [60-104] vs. 18 [8-41]). CONCLUSIONS: This pilot study suggests a positive relationship between journal-posted promotional tweets and article viewership.

Results of PRospect trial to Elucidate the utility of EchocarDiography-based Cardiac ouTput in acute heart failure (PREDICT).
Hiroyuki Iwano, Hiroto Utsunomiya, Kentaro Shibayama, Hidekazu Tanaka, Akihiro Isotani, Toshinari Onishi, Masaru Obokata, Masaki Izumo, Kenya Kusunose, Atsuko Furukawa, Masahiro Yamada, Takeshi Kitai, Tetsuari Onishi, Masayoshi Yamamoto, Shunsuke Sasaki, Kotaro Nochioka, Yoichi M Ito, Toshihisa Anzai
Journal of cardiology, 80, 3, 218, 225, 17 Mar. 2022, [International Magazine]
English, Scientific journal, BACKGROUND: The predictive value of echocardiographic parameters for early worsening heart failure (WHF), worsening of symptoms of heart failure requiring intensification of therapy during an admission for acute decompensated heart failure (ADHF), has not been elucidated. METHODS: Sixteen centers in Japan prospectively enrolled 303 ADHF hospitalized patients who did not receive positive inotropic agents as an initial therapy. Physical and Doppler echocardiographic examinations were performed before the initial therapy and the association of low output findings and occurrence of early WHF were tested. RESULTS: Early WHF occurred in 63 patients with a median duration of 6 (IQR: 2-23) hours from the administration of the initial therapy. In patients with left ventricular (LV) ejection fraction <40% (N = 153), echocardiographic stroke volume index, and cardiac index showed greater c-index [95% confidence interval, 0.71 (0.61-0.79) and 0.72 (0.63-0.80), respectively] compared to single low perfusion finding (symptomatic hypotension, reduced pulse pressure, and impaired mentation) other than cool extremities. When physical findings were combined (low perfusion score), the predictive ability improved to the similar levels of echocardiographic LV output parameters [c-index: 0.69 (0.60-0.76)]. However, addition of cardiac index significantly improved the prognostic ability when added to low perfusion score [0.82 (0.74-0.87), p < 0.001]. In contrast, in patients with LV ejection fraction ≥40% (N = 150), low perfusion score, rather than LV output parameters, was predictive of early WHF [c-index: 0.73 (0.56-0.85)]. CONCLUSIONS: We demonstrated the predictive value of echocardiographic LV output indices for early WHF in ADHF patients with LV systolic dysfunction. These data support the motivation for routine use of echocardiography for initial assessment of ADHF.

Circulation Journal Awards for the Year 2021.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 86, 3, 365, 375, 25 Feb. 2022, [Domestic magazines]
English, Scientific journal

Clinical Utility of Superior Vena Cava Flow Velocity Waveform Measured from the Subcostal Window for Estimating Right Atrial Pressure.
Michito Murayama, Sanae Kaga, Kazunori Okada, Hiroyuki Iwano, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Shingo Tsujinaga, Yasuyuki Chiba, Suguru Ishizaka, Ko Motoi, Kiwamu Kamiya, Mutsumi Nishida, Toshiyuki Nagai, Toshihisa Anzai
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, 35, 7, 727, 737, 09 Feb. 2022, [International Magazine]
English, Scientific journal, BACKGROUND: The superior vena cava (SVC) flow velocity waveform from the supraclavicular window reflects right atrial pressure (RAP) status. Recent guidelines have stated that the subcostal window is an alternative view for recording SVC flow, but the validity of this approach remains unclear. The aim of this study was to determine the usefulness of SVC flow evaluation from the subcostal window for estimating RAP. METHODS: Differences in SVC flow characteristics between opposite approaches were examined in 38 healthy adults. In 115 patients with cardiovascular diseases who underwent cardiac catheterization and echocardiography within 48 hours, the ratio of peak systolic to diastolic forward SVC flow (SVC-S/D) was measured, and the diagnostic ability of SVC-S/D for elevated RAP was tested. A validation cohort was used to confirm the diagnostic ability of SVC-S/D in 48 patients who underwent both cardiac catheterization and echocardiography within 24 hours. In 59 patients in the derivation and validation cohorts, the relationship between SVC flow and RAP was compared between the opposite windows. RESULTS: Both systolic and diastolic SVC flow velocities were higher in the subcostal than in the supraclavicular approach, and effect of position change on subcostal SVC-S/D was smaller than that on supraclavicular SVC-S/D in healthy adults. Measurement of SVC-S/D from the subcostal window was feasible in 98 patients (85%). RAP was inversely correlated with SVC-S/D (r = -0.50, P < .001) and was an independent determinant of SVC-S/D after adjustment for right ventricular systolic function (β = -0.48, P < .001). A cutoff value of 1.9 for SVC-S/D showed 85% sensitivity and 74% specificity in identifying elevated RAP. Additionally, SVC-S/D showed an incremental diagnostic value combined with inferior vena cava size and collapsibility (P = .006). When a cutoff value of SVC-S/D < 1.9 was applied to the validation cohort, it showed acceptable accuracy of 72% and incremental diagnostic value combined with inferior vena cava parameters (P = .033). SVC-S/D from the subcostal window correlated better with RAP than that from the supraclavicular window (P < .001, Meng's test). CONCLUSIONS: Measurement of SVC flow velocity from the subcostal window was feasible, and SVC-S/D from the subcostal window could be an additive parameter for estimating RAP.

Cardiac Power Output Is Independently and Incrementally Associated With Adverse Outcomes in Heart Failure With Preserved Ejection Fraction.
Tomonari Harada, Miho Yamaguchi, Kazunori Omote, Hiroyuki Iwano, Yoshifumi Mizuguchi, Shiro Amanai, Kuniko Yoshida, Toshimitsu Kato, Koji Kurosawa, Toshiyuki Nagai, Kazuaki Negishi, Toshihisa Anzai, Masaru Obokata
Circulation. Cardiovascular imaging, 15, 2, e013495, Feb. 2022, [International Magazine]
English, Scientific journal, BACKGROUND: Cardiac power output is a measure of cardiac performance, and its prognostic significance has been shown in heart failure (HF) with reduced ejection fraction. Patients with HF with preserved ejection fraction may have altered cardiac performance, but the prognostic relevance of cardiac power output is unknown. This study sought to determine the association between cardiac power output and clinical outcomes in HF with preserved ejection fraction and to compare its prognostic effect to other measures of cardiac performance including ventricular-arterial coupling and mechanical efficiency. METHODS: Cardiac power output normalized to left ventricular mass was assessed by echocardiography in 408 patients with HF with preserved ejection fraction. Load-independent contractility (end-systolic elastance), arterial elastance, its coupling (arterial elastance/end-systolic elastance), left ventricular global longitudinal strain, and mechanical efficiency (stroke work/pressure-volume area) were also estimated noninvasively. The primary end point was a composite of cardiovascular mortality or HF hospitalization. RESULTS: The primary composite outcome occurred in 84 patients during a median follow-up of 19.4 months. There was a dose-dependent association between cardiac power output and the composite outcomes, in which patients with the lowest tertile of cardiac power output had >3-fold risk than those with the highest tertile (hazard ratio, 3.04 [95% CI, 1.66-5.57]; P=0.0003). In a multivariable model, lower cardiac power output was independently associated with adverse outcomes (hazard ratio, 0.70 per 1 SD [95% CI, 0.49-0.97]; P=0.03). In contrast, left ventricular size, end-systolic elastance, arterial elastance, arterial elastance/end-systolic elastance ratio, and left ventricular mechanical efficiency were not associated with outcomes. Cardiac power output provided an incremental prognostic effect over the model based on clinical (age, gender, diastolic blood pressure, and atrial fibrillation) and echocardiographic markers (left atrial size, pulmonary pressures, global longitudinal strain, and the ratio of early diastolic mitral inflow velocity to early diastolic mitral annular tissue velocity; P=0.03). CONCLUSIONS: In patients with HF with preserved ejection fraction, cardiac power output was independently and incrementally associated with adverse outcomes whereas other markers of cardiac performance were not.

Editorial Statistics and Best Reviewers Award for 2021.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 86, 2, 173, 175, 25 Jan. 2022, [Domestic magazines]
English, Scientific journal

Left ventricular mass index-to-QRS-voltage ratio predicts outcomes in heart failure with preserved ejection fraction.
Yoshiharu Kinugasa, Kensuke Nakamura, Hiroko Kamitani, Masayuki Hirai, Kiyotaka Yanagihara, Masahiko Kato, Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Yasuchika Takeishi, Kazuhiro Yamamoto, Toshihisa Anzai
ESC heart failure, 9, 2, 1098, 1106, 25 Jan. 2022, [International Magazine]
English, Scientific journal, AIMS: Increased left ventricular mass index (LVMI) disproportionate to electrocardiographic QRS voltage has been reported to be associated with cardiac fibrosis and amyloid infiltration to myocardium. This study aimed to assess whether the LVMI-to-QRS-voltage ratio predicts clinical outcomes in heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, and prospective registration of Japanese patients hospitalized with HFpEF (EF ≥ 50%). LVMI was assessed by echocardiography using the cube formula. QRS voltage was assessed by Sokolow-Lyon voltage criteria. We divided 290 patients in the registry who met inclusion criteria into five groups according to the quintile values of their LVMI-to-QRS-voltage ratio. In the highest quintile group (≥71.8 g/m2 /mV), approximately 50% of the patients had concentric hypertrophy and 30% had eccentric hypertrophy. These patients had the highest proportion of atrial fibrillation (61.4%) and history of pacemaker implantation (12.1%) among the five groups (P < 0.05). During the mean follow-up of 587 ± 300 days, 31.4% of all patients met the composite endpoint of all-cause death or rehospitalization for HF. Even after adjustment for demographic and baseline variables, the highest quintile group had a significantly higher incidence of the composite endpoints than the lowest quintile group (<30.7 g/m2 /mV) (hazard ratio: 2.205, 95% confidence interval: 1.106-4.395, P < 0.05). CONCLUSIONS: A high LVMI-to-QRS-voltage ratio is independently associated with poor outcomes in patients with HFpEF.

Determinants of altered left ventricular suction in pre-capillary pulmonary hypertension.
Yasuyuki Chiba, Hiroyuki Iwano, Satonori Tsuneta, Shingo Tsujinaga, Brett Meyers, Pavlos Vlachos, Suguru Ishizaka, Ko Motoi, Hiroyuki Aoyagi, Yoji Tamaki, Asuka Tanemura, Michito Murayama, Shinobu Yokoyama, Masahiro Nakabachi, Hisao Nishino, Sanae Kaga, Kiwamu Kamiya, Hiroshi Ohira, Ichizo Tsujino, Toshihisa Anzai
European heart journal. Cardiovascular Imaging, 23, 10, 1399, 1406, 10 Jan. 2022, [International Magazine]
English, Scientific journal, AIMS: Although the left ventricular (LV) dysfunction in pre-capillary pulmonary hypertension (PH) has been recently recognized, the mechanism of LV dysfunction in this entity is not completely understood. We thus aimed to elucidate the determinants of intraventricular pressure difference (IVPD), a measure of LV suction, in pre-capillary PH. METHODS AND RESULTS: Right heart catheterization and echocardiography were performed in 86 consecutive patients with pre-capillary PH (57 ± 18 years, 85% female). IVPD was determined using colour M-mode Doppler to integrate the Euler equation. In overall, IVPD was reduced compared to previously reported value in normal subjects. In univariable analyses, QRS duration (P = 0.028), LV ejection fraction (P = 0.006), right ventricular (RV) end-diastolic area (P < 0.001), tricuspid annular plane systolic excursion (P = 0.004), and LV early-diastolic eccentricity index (P = 0.009) were associated with IVPD. In the multivariable analyses, RV end-diastolic area and LV eccentricity index independently determined the IVPD. CONCLUSION: Aberrant ventricular interdependence caused by RV enlargement could impair the LV suction. This study first applied echocardiographic IVPD, a reliable marker of LV diastolic suction, to investigate the mechanism of LV diastolic dysfunction in pre-capillary PH.

ドプラ心エコー法による肺動脈弁逆流重症度の過大評価の要因に関する検討　　　　　　　　　　　　　　　
本居 昂, 岩野 弘幸, 常田 慧徳, 村山 迪史, 加賀 早苗, 青柳 裕之, 玉置 陽生, 石坂 傑, 千葉 泰之, 辻永 真吾, 種村 明日香, 横山 しのぶ, 中鉢 雅大, 西野 久雄, 岡田 一範, 武田 充人, 安斉 俊久
日本成人先天性心疾患学会雑誌, 11, 1, 216, 216, 日本成人先天性心疾患学会, Jan. 2022
Japanese

Neoatherosclerosis with silent plaque rupture in a saphenous vein graft causing no re-flow phenomenon assessed by optical coherence tomography and histopathology.
Takao Konishi, Yuki Takahashi, Sho Kazui, Yutaro Yasui, Kohei Saiin, Seiichiro Naito, Sakae Takenaka, Yoshifumi Mizuguchi, Atsushi Tada, Yuta Kobayashi, Kazunori Omote, Takuma Sato, Kiwamu Kamiya, Toshiyuki Nagai, Shinya Tanaka, Toshihisa Anzai
Cardiology journal, 29, 4, 718, 719, 2022, [International Magazine]
English, Scientific journal

Vulnerable plaque derived from aspirated thrombi in recurrent acute coronary syndrome with familial hypercholesterolemia despite intensive lipid-lowering statin therapy.
Hiroyuki Natsui, Takao Konishi, Kohei Saiin, Youji Tamaki, Tomoya Sato, Sakae Takenaka, Atsushi Tada, Yoshifumi Mizuguchi, Yuta Kobayashi, Takuma Sato, Rui Kamada, Kiwamu Kamiya, Toshiyuki Nagai, Shinya Tanaka, Toshihisa Anzai
Cardiology journal, 29, 2, 362, 363, 2022, [International Magazine]
English, Scientific journal

Functional Tricuspid Regurgitation and Right Atrial Remodeling in Heart Failure With Preserved Ejection Fraction.
Tomonari Harada, Masaru Obokata, Kazunori Omote, Hiroyuki Iwano, Takahiro Ikoma, Kenya Okada, Kuniko Yoshida, Toshimitsu Kato, Koji Kurosawa, Toshiyuki Nagai, Toshihisa Anzai, Barry A Borlaug, Masahiko Kurabayashi
The American journal of cardiology, 162, 129, 135, 01 Jan. 2022, [International Magazine]
English, Scientific journal, Tricuspid regurgitation (TR) is common in patients with heart failure with preserved ejection fraction (HFpEF), but it has not been well characterized. We hypothesized that right atrial (RA) remodeling would be associated with TR in HFpEF, forming a type of atrial functional TR (AFTR). Echocardiography was performed in 328 patients with HFpEF. TR severity was defined using a guidelines-based approach. Ventricular functional TR was defined as the presence of right ventricular (RV) systolic pressure >50 mm Hg or RV dilation, and the remaining patients were classified as having AFTR if they had RA dilation or tricuspid annular enlargement. RA dilation was common (78%) in the significant TR group (more than mild), exceeding the prevalence of RV dilation (32%), and RA dilation was correlated with tricuspid annular diameter and TR vena contracta width (r = 0.67 and r = 0.70, both p <0.0001). Despite the absence of RV dilation and pulmonary hypertension, 38% of patients with significant TR had AFTR. Patients with AFTR and those with ventricular functional TR displayed higher heart failure hospitalization rates than those with nonsignificant TR (adjusted hazard ratios, 2.45 and 4.31; 95% confidence interval 1.12 to 5.35 and 2.44 to 7.62, p = 0.02 and p <0.0001, respectively). In conclusion, TR in HFpEF is related to RA remodeling, and the presence of AFTR was associated with poor clinical outcomes. The current data highlight the importance of RA remodeling in the pathophysiology of TR in HFpEF.

Messages From the Editor-in-Chief.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 86, 1, 1, 1, 24 Dec. 2021, [Domestic magazines]
English, Scientific journal

The Circulation Journal Official Impact Factor and the Most Frequently Cited Papers in 2020.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 86, 1, 2, 5, 24 Dec. 2021, [Domestic magazines]
English, Scientific journal

Molecular ratio of mature B-type natriuretic peptide in acute heart failure: an indicator for ventricular contractile recovery.
Akihisa Kimura, Hiroyuki Takahama, Toshio Nishikimi, Seiji Takashio, Tomohiro Hayashi, Chiaki Nagai-Okatani, Yasuaki Nakagawa, Satoshi Yasuda, Toshihisa Anzai, Naoto Minamino, Chisato Izumi
ESC heart failure, 8, 6, 5617, 5621, Dec. 2021, [International Magazine]
English, Scientific journal, AIMS: The methodology to distinguish between the heart failure (HF) with recovered ejection fraction (HFrecEF) and those with continuously reduced ejection fraction (EF) (HFcrEF) on admission has not been established. We recently demonstrated that the ratio of plasma levels of pro-B-type natriuretic peptide (proBNP) to total BNP (proBNP plus mature BNP) is decreased on admission in patients with mild acute HF, but not in severe acute HF as a compensatory mechanism for activating cyclic GMP via increases of bioactive mature BNP. We aimed to test the hypothesis that the ratio of bioactive mature BNP to total BNP is associated with reverse remodelling capacity in patients with HF with reduced EF. METHODS AND RESULTS: Plasma proBNP and total BNP were measured in patients with acute decompensated HF by using specific and sensitive enzyme immunochemiluminescent assay. Estimated percent mature BNP (%emBNP) was calculated as ([total BNP - proBNP]/total BNP) × 100. We retrospectively identified the patients with reduced EF (≤40%, on admission) who had echocardiographic data after discharge (n = 93). We defined patients with increased EF by >10% during the follow-up term (median, 545 days) after the admission as HFrecEF group. We compared patient characteristics, %emBNP, and other biomarkers between HFrecEF and HFcrEF. Of the enrolled patients with HFrecEF (n = 32) and HFcrEF (n = 61), on admission, %emBNP was significantly higher in HFrecEF than in HFcrEF (44.1% vs. 36.9%; P < 0.05). There were no significant differences in left ventricular EF on admission between the two groups. The univariate analysis revealed that %emBNP on admission was associated with HFrecEF occurrence rate (P < 0.05), in contrast both total BNP and high-sensitive cardiac troponin-T levels were not associated with HFrecEF occurrence rate. CONCLUSIONS: The ratio of mature BNP to total BNP in plasma at the time of hospital admission may be predictive of left ventricular contractile recovery. Preservation of the capacity to convert proBNP to mature BNP, but not myocardial injury itself, is associated with future ventricular contractile recovery.

Reduction of tethering distance by papillary muscle tugging approximation with mitral valve replacement for non-ischemic functional mitral regurgitation induces left ventricular reverse remodeling
Takahiro Ishigaki, Satoru Wakasa, Yasushige Shingu, Yohei Ohkawa, Akira Yamada, Toshihisa Anzai, Yoshiro Matsui
Journal of Cardiology, 79, 4, 530, 536, Elsevier BV, Nov. 2021, [International Magazine]
English, Scientific journal, BACKGROUND: Functional mitral regurgitation (FMR) is caused by left ventricular (LV) remodeling and subsequent tethering of the mitral valve (MV). If LV remodeling is irreversibly advanced, it could not be attenuated by the MV procedure alone, although the additional subvalvular procedure could induce LV reverse remodeling by forcibly reducing MV tethering. This study aimed to assess the anti-tethering effect of papillary muscle tugging approximation (PMTA) on LV reverse remodeling after mitral valve replacement (MVR) for non-ischemic FMR. METHODS: The study subjects were 19 patients who underwent MVR with and without PMTA [MVR + PMTA (n = 11) and MVR alone (n = 8), respectively] for non-ischemic FMR. The tethering distance (TD) and LV end-systolic volume (ESV) at the preoperative, postoperative, and follow-up periods were assessed in terms of their correlation and time-dependent changes. The intra-LV energy efficiency was also evaluated through vector flow mapping analysis. RESULTS: TD and ESV were comparable between both procedures preoperatively and did not change after MVR alone. In MVR + PMTA, however, a significant decrease was identified in TD and ESV at the early postoperative and follow-up periods, respectively [TD = 48, 30, and 31 mm (p < 0.001) and ESV = 159, 133, and 82 mL (p < 0.001) at the preoperative, postoperative, and follow-up periods, respectively]. Finally, at follow-up, the extent of change from the preoperative value in ESV significantly correlated with that in TD (ρ = 0.81, p < 0.001 for overall; ρ = 0.93, p < 0.001 for MVR + PMTA; ρ = 0.86, p = 0.011 for MVR alone). The ratio of TD to ESV was also significantly correlated with systolic energy loss to LV stroke work after MVR + PMTA (ρ = 0.81, p = 0.015). CONCLUSIONS: PMTA for non-ischemic FMR could induce LV reverse remodeling depending on the extent of postoperative TD reduction. A smaller TD to ESV was associated with a higher intra-LV energy efficiency after PMTA + MVR.

Performance of the H2FPEF and the HFA-PEFF scores for the diagnosis of heart failure with preserved ejection fraction in Japanese patients: A report from the Japanese multicenter registry.
Atsushi Tada, Toshiyuki Nagai, Kazunori Omote, Hiroyuki Iwano, Shingo Tsujinaga, Kiwamu Kamiya, Takao Konishi, Takuma Sato, Hirokazu Komoriyama, Yuta Kobayashi, Sakae Takenaka, Yoshifumi Mizuguchi, Tomoya Sato, Kazuhiro Yamamoto, Tsutomu Yoshikawa, Yoshihiko Saito, Toshihisa Anzai
International journal of cardiology, 342, 43, 48, 01 Nov. 2021, [International Magazine]
English, Scientific journal, BACKGROUND: Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Although the H2FPEF score and HFA-PEFF algorithm have been proposed for diagnosing HFpEF, previous validation studies were conducted in stable chronic heart failure (HF). Moreover, information on their applicability in the Asian population is limited. We sought to investigate these scores' diagnostic performance for HFpEF in Japanese patients recently hospitalized due to acute decompensated HF. METHODS: We examined patients with HFpEF recently hospitalized with acute decompensated HF from a nationwide HFpEF-specific multicenter registry (HFpEF group) and control patients who underwent echocardiography to investigate the cause of dyspnea in our hospital (Non-HFpEF group). RESULTS: The studied population included 372 patients (194 HFpEF group and 178 Non-HFpEF group; HFpEF prevalence, 52%). A high H2FPEF score (6-9 points) could diagnose HFpEF with a high specificity of 97% and a positive predictive value (PPV) of 94%, and a low H2FPEF score (0-1 point) could rule out HFpEF with a high sensitivity of 97% and a negative predictive value (NPV) of 93%. HFpEF could be diagnosed with a high HFA-PEFF score (5-6 points) (specificity, 84%; PPV, 82%) or ruled out with a low HFA-PEFF score (0-1 point) (sensitivity, 99%; NPV, 89%). The H2FPEF score was significantly superior to the HFA-PEFF score in diagnostic accuracy (area under the curve: 0.89 vs. 0.82, respectively, p = 0.004). CONCLUSIONS: The H2FPEF and the HFA-PEFF scores had acceptable diagnostic accuracy in diagnosing HFpEF in Japanese patients.

Hospitalization for heart failure in the USA, UK, Taiwan and Japan: an international comparison of administrative health records on 417,385 individual patients.
Varun Sundaram, Toshiyuki Nagai, Chern-En Chiang, Yogesh Nv Reddy, Tze-Fan Chao, Rosita Zakeri, Chloe Bloom, Michikazu Nakai, Kunihiro Nishimura, Chung-Lieh Hung, Yoshihiro Miyamoto, Satoshi Yasuda, Amitava Banerjee, Toshihisa Anzai, Daniel I Simon, Sanjay Rajagopalan, John Gf Cleland, Jayakumar Sahadevan, Jennifer K Quint
Journal of cardiac failure, 28, 3, 353, 366, 08 Oct. 2021, [International Magazine]
English, Scientific journal, BACKGROUND: Registries show international variations in the characteristics and outcome of patients with heart failure (HF) but national samples are rarely large, and case-selection may be biased due to enrolment in academic centres. National administrative datasets provide large samples with a low risk of bias. In this study, we compared the characteristics, healthcare resource utilization (HRU) and outcomes of patients with primary HF hospitalizations (HFH) using electronic health records (EHR) from four high-income countries (USA, UK, Taiwan, Japan) on three continents. METHODS AND RESULTS: We used EHR to identify unplanned HFH between 2012-2014. We identified 231,512, 10,991, 36,900 and 133,982 patients with a primary HFH from USA, UK, Taiwan and Japan, respectively. HFH per 100,000 population was highest in USA and lowest in Taiwan. Patients in Taiwan and Japan were older but fewer were obese or had chronic kidney disease. LOHS was shortest in USA (median 4 days) and longer in UK, Taiwan and Japan (medians 7, 9 and 17 days, respectively). HRU during hospitalization was highest in Japan and lowest in UK. Crude and direct standardized in-hospital mortality was lowest in USA (direct standardized rates: 1.8 [95%CI:1.7-1.9]%)and progressively higher in Taiwan (direct standardized rates: 3.9 [95%CI:3.8-4.1]%), UK (direct standardized rates: 6.4 [95%CI:6.1-6.7]%) and Japan (direct standardized rates: 6.7 [95%CI:6.6-6.8]%). 30-day all-cause (25.8%) and HF (7.2%) readmissions were highest in USA and lowest in Japan (11.9% and 5.1% respectively). CONCLUSION: Marked international variations in patient characteristics, HRU and clinical outcome exist; understanding them might inform health care policy and international trial design.

Sudden death after inappropriate shocks of implantable cardioverter defibrillator in a catecholaminergic polymorphic ventricular tachycardia case with a novel RyR2 mutation.
Hideki Itoh, Takashi Murayama, Nagomi Kurebayashi, Seiko Ohno, Takuya Kobayashi, Yusuke Fujii, Masaya Watanabe, Haruo Ogawa, Toshihisa Anzai, Minoru Horie
Journal of electrocardiology, 69, 111, 118, 07 Oct. 2021, [International Magazine]
English, Scientific journal, BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic syndrome and a cause of exercise-related sudden death. CPVT has been reported to be caused by gain of function underlying a mutation of cardiac ryanodine receptor (RyR2). METHODS: In a family with a CPVT patient, genomic DNA was extracted from peripheral blood lymphocytes, and the RyR2 gene underwent target gene sequence using MiSeq. The activity of wild-type (WT) and mutant RyR2 channel were evaluated by monitoring Ca2+ signals in HEK293 cells expressing WT and mutant RyR2. We investigated a role of a RyR2 mutation in the recent tertiary structure of RyR2. RESULTS: Though a 17-year-old man diagnosed as CPVT had implantable cardioverter defibrillator (ICD) and was going to undergo catheter ablation for the control of paroxysmal atrial fibrillation, he suddenly died at the age of twenty-one because of ventricular fibrillation which was spontaneously developed after maximum inappropriate ICD shocks against rapid atrial fibrillation. The genetic test revealed a de novo RyR2 mutation, Gln4936Lys in mosaicism which was located at the α-helix interface between U-motif and C-terminal domain. In the functional analysis, Ca2+ release from endoplasmic reticulum via the mutant RyR2 significantly increased than that from WT. CONCLUSION: A RyR2 mutation, Gln4936Lys, to be documented in a CPVT patient with exercise-induced ventricular tachycardias causes an excessive Ca2+ release from the sarcoplasmic reticulum which corresponded to clinical phenotypes of CPVT. The reduction of inappropriate shocks of ICD is essential to prevent unexpected sudden death in patients with CPVT.

Paravalvular leak vanishing at end-diastole during transcatheter aortic valve replacement.
Yoji Tamaki, Shingo Tsujinaga, Hiroyuki Iwano, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Journal of echocardiography, 21, 2, 81, 82, 06 Oct. 2021, [Domestic magazines]
English, Scientific journal

Influence of left ventricular systolic dysfunction on occurrence of pulsus tardus in patients with aortic stenosis.
Suguru Ishizaka, Hiroyuki Iwano, Ko Motoi, Yasuyuki Chiba, Shingo Tsujinaga, Asuka Tanemura, Michito Murayama, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Kazunori Okada, Sanae Kaga, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Journal of cardiology, 78, 4, 322, 327, Oct. 2021, [International Magazine]
English, Scientific journal, BACKGROUND: Although the time difference between peak of left ventricular (LV) and aortic systolic pressures (TLV-Ao), which is considered to in part reflect pulsus tardus, is reported to be associated with clinical outcome in aortic stenosis (AS), its physiological determinants remain to be elucidated. We hypothesized that not only AS severity but also LV systolic dysfunction could be associated with occurrence of pulsus tardus. METHODS: TLV-Ao was measured by simultaneous LV and aortic pressure tracing in 74 AS patients and prolonged TLV-Ao was defined as ≥66 ms according to the previous report. Mean transaortic valvular pressure gradient (mPG) and effective orifice area index (EOAI) were estimated by Doppler echocardiography and severe AS was defined as EOAI ≤0.60 cm2/m2. Global longitudinal strain (GLS) was measured by using speckle-tracking method. RESULTS: Although a weak correlation was observed between EOAI and TLV-Ao, there was substantial population showing discordance between the parameters: severe AS despite normal TLV-Ao (10 of 47 patients) and moderate AS despite prolonged TLV-Ao (9 of 17 patients). In severe AS, mPG was significantly higher in patients showing prolonged TLV-Ao (57±20 vs 36±10 mmHg, p<0.0001) whereas GLS was comparable between the groups (-15.2±3.5% vs -14.8±3.2%). In contrast, in moderate AS, GLS was significantly smaller in patients showing prolonged TLV-Ao (-12.6±4.7% vs -17.4±3.4%, p=0.0271) while mPG was comparable (34±7 mmHg vs 35±8 mmHg). Multivariable analysis revealed that not only mPG but also GLS was an independent determinant of TLV-Ao. CONCLUSIONS: The occurrence of pulsus tardus could be associated with not only AS severity but also LV systolic dysfunction in AS patients.

Influence of Left Ventricular Function on the "Aortic Regurgitation Index" Proposed for the Hemodynamic Assessment of Postprocedural Aortic Regurgitation.
Hideaki Kanzaki, Makoto Amaki, Atsushi Okada, Hiroyuki Takahama, Chisato Izumi, Toshihisa Anzai
International heart journal, 62, 5, 1019, 1025, 30 Sep. 2021, [Domestic magazines]
English, Scientific journal, The aortic regurgitation (AR) index, proposed as an objective indicator of postprocedural AR, decreases in proportion to AR severity, besides reportedly providing additional prognostic information. Meanwhile, left ventricular (LV) function has also been considered an essential prognostic factor. This study aimed to clarify whether LV function affected the AR index using cardiac catheterization data.A retrospective study was performed in patients whose LV function was evaluated using a micromanometer-tipped catheter. Patients with grade 2 or higher AR were excluded to explore non-AR factors affecting the AR index value. The AR index was calculated as a ratio of the gradient between the aortic diastolic blood pressure (DBP) and the LV end-diastolic pressure (EDP) to the aortic systolic blood pressure (SBP): AR Index = [ (DBP - LVEDP) / SBP] × 100.A total of 64 patients [age, 62 (interquartile range: 48-70) years; LV ejection fraction, 19% (16%-26%) ] were examined. AR index values ranged from 18.3 to 68.6. Despite having no AR, two patients displayed an AR index < 25, indicating significant AR. Multiple-regression analysis revealed that LV diastolic stiffness (β = -0.750, P < 0.001), LV max dP/dt (β = -0.296, P = 0.006), and heart rate (β = 0.284, P = 0.011) were independent determinants of the AR index value.Patients with impaired LV diastolic function and preserved systolic function had low AR index values. The additional prognostic information of the AR index may be related to LV diastolic function.

Application of the proximal isovelocity surface area method for estimation of the effective orifice area in aortic stenosis.
Masahiro Nakabachi, Hiroyuki Iwano, Michito Murayama, Hisao Nishino, Shinobu Yokoyama, Shingo Tsujinaga, Yasuyuki Chiba, Suguru Ishizaka, Ko Motoi, Kazunori Okada, Sanae Kaga, Mutsumi Nishida, Takanori Teshima, Toshihisa Anzai
Heart and vessels, 37, 4, 638, 646, 25 Sep. 2021, [Domestic magazines]
English, Scientific journal, Although the echocardiographic effective orifice area (EOA) calculated using the continuity equation is widely used for the assessment of severity in aortic stenosis (AS), the existence of high flow velocity at the left ventricular outflow tract (LVOT) potentially causes its overestimation. The proximal isovelocity surface area (PISA) method could be an alternative tool for the estimation of EOA that limits the influence of upstream flow velocity. EOA was calculated using the continuity equation (EOACont) and PISA method (EOAPISA), respectively, in 114 patients with at least moderate AS. The geometric orifice area (GOA) was also measured using the planimetry method in 51 patients who also underwent three-dimensional transesophageal echocardiography. Patients were divided into two groups according to the median LVOT flow velocity. EOAPISA could be obtained in 108 of the 114 patients (95%). Although there was a strong correlation between EOACont and EOAPISA (r = 0.78, P < 0.001), EOACont was statistically significantly larger than EOAPISA (0.86 ± 0.33 vs 0.75 ± 0.29 cm2, P < 0.001). Both EOACont and EOAPISA similarly correlated with GOA (r = 0.70, P < 0.001 and r = 0.77, P < 0.001, respectively). However, a fixed bias, which is hydrodynamically supposed to exist between EOA and GOA, was not observed between EOACont and GOA. In contrast, there was a negative fixed bias between EOAPISA and GOA with smaller EOAPISA than GOA. The difference between EOACont and GOA was significantly greater with a larger EOACont relative to GOA in patients with high LVOT flow velocity than in those without (0.16 ± 0.25 vs - 0.07 ± 0.10 cm2, P < 0.001). In contrast, the difference between EOAPISA and GOA was consistent regardless of the LVOT flow velocity (- 0.07 ± 0.12 vs - 0.07 ± 0.15 cm2, P = 0.936). The PISA method was applied to estimate EOA in patients with AS. EOAPISA could be an alternative parameter for AS severity grading in patients with high LVOT flow velocity in whom EOACont would potentially overestimate the orifice area.

Association of high serum soluble interleukin 2 receptor levels with risk of adverse events in cardiac sarcoidosis.
Yuta Kobayashi, Takuma Sato, Toshiyuki Nagai, Kenji Hirata, Satonori Tsuneta, Yoshiya Kato, Hirokazu Komoriyama, Kiwamu Kamiya, Takao Konishi, Kazunori Omote, Hiroshi Ohira, Kohsuke Kudo, Satoshi Konno, Toshihisa Anzai
ESC heart failure, 8, 6, 5282, 5292, 12 Sep. 2021, [International Magazine]
English, Scientific journal, AIMS: Although soluble interleukin 2 receptor (sIL-2R) is a potentially useful biomarker in the diagnosis and evaluation of disease severity in patients with sarcoidosis, its prognostic implication in patients with cardiac sarcoidosis (CS) is unclear. We sought to investigate whether sIL-2R was associated with clinical outcomes and to clarify the relationship between sIL-2R levels and disease activity in patients with CS. METHODS AND RESULTS: We examined 83 consecutive patients with CS in our hospital who had available serum sIL-2R data between May 2003 and February 2020. The primary outcome was a composite of advanced atrioventricular block, ventricular tachycardia or ventricular fibrillation, heart failure hospitalization, and all-cause death. Inflammatory activity in the myocardium and lymph nodes was assessed by 18 F-fluorideoxyglucose positron emission tomography/computed tomography. During a median follow-up period of 2.96 (IQR 2.24-4.27) years, the primary outcome occurred in 24 patients (29%). Higher serum sIL-2R levels (>538 U/mL, the median) were significantly related to increased incidence of primary outcome (P = 0.037). Multivariable Cox regression analysis showed that a higher sIL-2R was independently associated with an increased subsequent risk of adverse events (HR 3.71, 95% CI 1.63-8.44, P = 0.002), even after adjustment for significant covariates. sIL-2R levels were significantly correlated to inflammatory activity in lymph nodes (r = 0.346, P = 0.003) but not the myocardium (r = 0.131, P = 0.27). CONCLUSIONS: Increased sIL-2R is associated with worse long-term clinical outcomes accompanied by increased systemic inflammatory activity in CS patients.

心臓サルコイドーシス患者における血清可溶性インターロイキン2レセプター高値は長期予後と関連する　　　　　　　　　　　　　　　
小林 雄太, 永井 利幸, 加藤 喜哉, 小森山 弘和, 神谷 究, 小西 崇夫, 佐藤 琢真, 安斉 俊久
日本心臓病学会学術集会抄録, 69回, O, 282, (一社)日本心臓病学会, Sep. 2021
Japanese

慢性心不全における右室cardiac power outputの意義　　　　　　　　　　　　　　　
千葉 泰之, 岩野 弘幸, 本居 昂, 石坂 傑, 辻永 真吾, 村山 迪史, 横山 しのぶ, 中鉢 雅大, 西野 久雄, 岡田 一範, 加賀 早苗, 神谷 究, 永井 利幸, 安斉 俊久
日本心臓病学会学術集会抄録, 69回, O, 029, (一社)日本心臓病学会, Sep. 2021
Japanese

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, Sep. 2021
Japanese

Relevance of early-diastolic mitral regurgitation in dilated heart.
Asuka Tanemura, Michito Murayama, Hiroyuki Iwano, Yasuyuki Chiba, Mutsumi Nishida, Takanori Teshima, Toshihisa Anzai
Journal of echocardiography, 21, 1, 50, 52, 30 Aug. 2021, [Domestic magazines]
English, Scientific journal

心筋梗塞後偽性仮性左室瘤に収縮性心膜炎の合併が考えられた1例
甲谷 太郎, 安斉 俊久
循環器専門医, 30, 118, 123, (一社)日本循環器学会, Aug. 2021
Japanese

Long-Term Prognostic Significance of Ventricular Repolarization Dispersion in Patients with Cardiac Sarcoidosis.
Yuta Kobayashi, Toshiyuki Nagai, Sakae Takenaka, Yoshiya Kato, Hirokazu Komoriyama, Nobutaka Nagano, Kiwamu Kamiya, Takao Konishi, Takuma Sato, Kazunori Omote, Shingo Tsujinaga, Hiroyuki Iwano, Kengo Kusano, Satoshi Yasuda, Hisao Ogawa, Hatsue Ishibashi-Ueda, Toshihisa Anzai
The American journal of cardiology, 152, 125, 131, 01 Aug. 2021, [International Magazine]
English, Scientific journal, Cardiac sarcoidosis (CS) is frequently complicated by fatal ventricular arrhythmias. T-peak to T-end interval to QT interval ratio (TpTe/QT) on electrocardiograms (ECG) was proposed as a marker of ventricular repolarization dispersion. Although this ratio could be associated with the incidence of ventricular arrhythmias in cardiovascular diseases, its prognostic implication in patients with CS is unclear. We sought to investigate whether TpTe/QT was associated with long-term clinical outcomes in patients with CS. Ninety consecutive patients with CS in 2 tertiary hospitals who had ECG data before initiation of immunosuppressive therapy between November 1995 and March 2019 were examined. The primary outcome was a composite of advanced atrioventricular block, ventricular tachycardia or ventricular fibrillation (VT/VF), heart failure hospitalization, and all-cause death. During a median follow-up period of 4.70 (interquartile range 2.06-7.23) years, the primary outcome occurred in 21 patients (23.3%). Survival analyses revealed that the primary outcome (p < 0.001), especially VT/VF or sudden cardiac death (p = 0.002), occurred more frequently in patients with higher TpTe/QT (≥ 0.242, the median) than in those with lower TpTe/QT. Multivariable Cox regression analysis showed that a higher TpTe/QT was independently associated with increased subsequent risk of adverse events (hazard ratio1.11, 95% confidence interval 1.03-1.20, p = 0.008) even after adjustment for the significant covariates. In conclusion, a higher TpTe/QT was associated with worse long-term clinical outcomes, especially fatal ventricular arrhythmic events, in patients with cardiac sarcoidosis, suggesting the importance of assessing TpTe/QT as a surrogate for risk stratification in these patients.

Fulminant cardiac and renal sarcoidosis revealed by electron microscope: challenging aspect of diagnosis
Seiichiro Naito, Shingo Tsujinaga, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
European Heart Journal - Case Reports, 5, 11, ytab298, Oxford University Press (OUP), 28 Jul. 2021, [International Magazine]
English, Scientific journal

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, 25, 1, 37, 41, Elsevier BV, Jul. 2021, [Domestic magazines]
English, Scientific journal, Although a hybrid procedure involving surgical access may be feasible for epicardial catheter ablation in individuals with prior cardiac surgery, surgical approaches in thoracotomy are important in patients with advanced adhesions. We performed an epicardial ventricular tachycardia (VT) ablation in a patient with dilated phase hypertrophic cardiomyopathy after left ventricular reconstruction. We gained surgical epicardial access via lateral thoracotomy based on the anticipated VT circuit in the apical anteroseptal area, which was estimated using prior endocardial mapping. The remaining epicardial myocardium around the surgical incision was involved in the central isthmus, and the VT was eliminated by radiofrequency catheter ablation. .

Simple Two-Dimensional Echocardiographic Scoring System for the Estimation of Left Ventricular Filling Pressure.
Michito Murayama, Hiroyuki Iwano, Hisao Nishino, Shingo Tsujinaga, Masahiro Nakabachi, Shinobu Yokoyama, Miho Aiba, Kazunori Okada, Sanae Kaga, Miwa Sarashina, Yasuyuki Chiba, Suguru Ishizaka, Ko Motoi, Mutsumi Nishida, Hitoshi Shibuya, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, 34, 7, 723, 734, Jul. 2021, [International Magazine]
English, Scientific journal, BACKGROUND: When left ventricular filling pressure (LVFP) increases, the mitral valve opens early and precedes tricuspid valve opening in early diastole. The authors hypothesized that a visually assessed time sequence of atrioventricular valve opening could become a new marker of elevated LVFP. The aim of this study was to test the diagnostic ability of a novel echocardiographic scoring system, the visually assessed time difference between mitral valve and tricuspid valve opening (VMT) score, in patients with heart failure. METHODS: One hundred nineteen consecutive patients who underwent cardiac catheterization within 24 hours of echocardiographic examination were retrospectively analyzed as a derivation cohort. In addition, a prospective study was conducted to validate the diagnostic ability of the VMT score in 50 patients. Elevated LVFP was defined as mean pulmonary artery wedge pressure (PAWP) ≥ 15 mm Hg. The time sequence of atrioventricular valve opening was visually assessed and scored (0 = tricuspid valve first, 1 = simultaneous, 2 = mitral valve first). When the inferior vena cava was dilated, 1 point was added, and VMT score was ultimately graded as 0 to 3. Cardiac events were recorded for 1 year after echocardiography. RESULTS: In the derivation cohort, PAWP was elevated with higher VMT scores (score 0, 10 ± 5; score 1, 12 ± 4; score 2, 22 ± 8; score 3, 28 ± 4 mm Hg; P < .001, analysis of variance). VMT score ≥ 2 predicted elevated PAWP with accuracy of 86% and showed incremental predictive value over clinical variables and guideline-recommended diastolic function grading. These observations were confirmed in the prospective validation cohort. Importantly, VMT score ≥ 2 discriminated elevated PAWP with accuracy of 82% in 33 patients with monophasic left ventricular inflow in the derivation cohort. Kaplan-Meier analysis demonstrated that patients with VMT scores ≥ 2 were at higher risk for cardiac events than those with VMT scores ≤ 1 (P < .001). CONCLUSIONS: VMT scoring could be a novel additive marker of elevated LVFP and might also be associated with adverse outcomes in patients with heart failure.

Blood flow dynamics with four-dimensional flow cardiovascular magnetic resonance in patients with aortic stenosis before and after transcatheter aortic valve replacement.
Hirokazu Komoriyama, Kiwamu Kamiya, Toshiyuki Nagai, Noriko Oyama-Manabe, Satonori Tsuneta, Yuta Kobayashi, Yoshiya Kato, Miwa Sarashina, Kazunori Omote, Takao Konishi, Takuma Sato, Shingo Tsujinaga, Hiroyuki Iwano, Yasushige Shingu, Satoru Wakasa, Toshihisa Anzai
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance, 23, 1, 81, 81, 28 Jun. 2021, [International Magazine]
English, Scientific journal, BACKGROUND: Pre- and post-procedural hemodynamic changes which could affect adverse outcomes in aortic stenosis (AS) patients who undergo transcatheter aortic valve replacement (TAVR) have not been well investigated. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) enables accurate analysis of blood flow dynamics such as flow velocity, flow pattern, wall shear stress (WSS), and energy loss (EL). We sought to examine the changes in blood flow dynamics of patients with severe AS who underwent TAVR. METHODS: We examined 32 consecutive severe AS patients who underwent TAVR between May 2018 and June 2019 (17 men, 82 ± 5 years, median left ventricular ejection fraction 61%, 6 self-expanding valve), after excluding those without CMR because of a contraindication or inadequate imaging from the analyses. We analyzed blood flow patterns, WSS and EL in the ascending aorta (AAo), and those changes before and after TAVR using 4D flow CMR. RESULTS: After TAVR, semi-quantified helical flow in the AAo was significantly decreased (1.4 ± 0.6 vs. 1.9 ± 0.8, P = 0.002), whereas vortical flow and eccentricity showed no significant changes. WSS along the ascending aortic circumference was significantly decreased in the left (P = 0.038) and left anterior (P = 0.033) wall at the basal level, right posterior (P = 0.011) and left (P = 0.010) wall at the middle level, and right (P = 0.012), left posterior (P = 0.019) and left anterior (P = 0.028) wall at the upper level. EL in the AAo was significantly decreased (15.6 [10.8-25.1 vs. 25.8 [18.6-36.2]] mW, P = 0.012). Furthermore, a significant negative correlation was observed between EL and effective orifice area index after TAVR (r = - 0.38, P = 0.034). CONCLUSIONS: In severe AS patients undergoing TAVR, 4D flow CMR demonstrates that TAVR improves blood flow dynamics, especially when a larger effective orifice area index is obtained.

Takotsubo Syndrome After Transcatheter Mitral Valve Repair.
Takahide Kadosaka, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 85, 7, 1100, 1100, 25 Jun. 2021, [Domestic magazines]
English, Scientific journal

Applicability of the AHA/ACC/HRS Guideline for Implantable Cardioverter Defibrillator Implantation in Japanese Patients With Cardiac Sarcoidosis.
Sakae Takenaka, Yuta Kobayashi, Toshiyuki Nagai, Yoshiya Kato, Hirokazu Komoriyama, Nobutaka Nagano, Kiwamu Kamiya, Takao Konishi, Takuma Sato, Kazunori Omote, Yoshifumi Mizuguchi, Atsushi Tada, Tomoya Sato, Hiroyuki Iwano, Kengo Kusano, Hatsue Ishibashi-Ueda, Toshihisa Anzai
JACC. Clinical electrophysiology, 7, 11, 1410, 1418, (一社)日本心臓病学会, 22 Jun. 2021, [International Magazine]
English, Scientific journal

Improved Mitochondria! Function by Luseogliflozin Prevents Pancreatic Beta-Cell Damage
Yuki Yamauchi, Akinobu Nakamura, Takashi Yokota, Kiyohiko Takahashi, Shinichiro Kawata, Kazuhisa Tsuchida, Kazuno Omori, Hiroshi Nomoto, Hiraku Kameda, Kyuyong Cho, Toshihisa Anzai, Shinya Tanaka, Yasuo Terauchi, Hideaki Miyoshi, Tatsuya Atsumi
DIABETES, 70, Jun. 2021
English

Prognostic value of admission serum magnesium in acute myocardial infarction complicated by malignant ventricular arrhythmias.
Yoshifumi Mizuguchi, Takao Konishi, Toshiyuki Nagai, Tomoya Sato, Sakae Takenaka, Atsushi Tada, Yuta Kobayashi, Hirokazu Komoriyama, Yoshiya Kato, Kazunori Omote, Takuma Sato, Kiwamu Kamiya, Shingo Tsujinaga, Hiroyuki Iwano, Kenjiro Kikuchi, Shinya Tanaka, Toshihisa Anzai
The American journal of emergency medicine, 44, 100, 105, Jun. 2021, [International Magazine]
English, Scientific journal, OBJECTIVES: Although electrolyte abnormalities are related to worse clinical outcomes in patients with acute myocardial infarction (AMI), little is known about the association between admission serum magnesium level and adverse events in AMI patients complicated by out-of-hospital cardiac arrest presenting with malignant ventricular arrhythmias (OHCA-MVA). We investigated the prognostic value of serum magnesium level on admission in these patients. METHODS: We retrospectively analyzed the data of 165 consecutive reperfused AMI patients complicated with OHCA-MVA between April 2007 and February 2020 in our university hospital. Serum magnesium concentration was measured on admission. The primary outcome was in-hospital death. RESULTS: Fifty-four patients (33%) died during hospitalization. Higher serum magnesium level was significantly related to in-hospital death (Fine & Gray's test; p < 0.001). In multivariable logistic regression analyses, serum magnesium level on admission was independently associated with in-hospital death (hazard ratio 2.68, 95% confidence interval 1.24-5.80) even after adjustment for covariates. Furthermore, the incidences of cardiogenic shock necessitating an intra-aortic balloon pump (p = 0.005) or extracorporeal membrane oxygenation (p < 0.001), tracheal intubation (p < 0.001) and persistent vegetative state (p = 0.002) were significantly higher in patients with higher serum magnesium level than in those with lower serum magnesium level. CONCLUSIONS: In reperfused AMI patients complicated by OHCA-MVA, admission serum magnesium level might be a potential surrogate marker for predicting in-hospital death.

Anemia has an impact on prognosis in heart failure with preserved ejection fraction with mild chronic kidney disease.
Keisuke Okuno, Yoshiro Naito, Masanori Asakura, Masataka Sugahara, Tetsuo Horimatsu, Seiki Yasumura, Saki Tahara, Toshiyuki Nagai, Yoshihiko Saito, Tsutomu Yoshikawa, Tohru Masuyama, Masaharu Ishihara, Toshihisa Anzai
International journal of cardiology. Heart & vasculature, 34, 100796, 100796, Jun. 2021, [International Magazine]
English, Scientific journal, Background: Anemia and chronic kidney disease (CKD) are common in patients with heart failure with preserved left ventricular fraction (HFpEF). However, it is entirely unknown about the impact of anemia on prognosis in HFpEF patients with CKD. In this study, we investigated the impact of anemia on prognosis and the optimal hemoglobin (Hb) levels to predict prognosis in HFpEF patients with CKD. Methods and Results: We prospectively examined 523 consecutive HFpEF patients enrolled in Japanese heart failure syndrome with preserved ejection fraction registry. CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 mL /min/1.73 m2. The prevalence rate of anemia was 78% in HFpEF patients with CKD by using the World Health Organization criteria. Kaplan-Meier analysis for all-cause mortality and heart failure rehospitalization demonstrated that anemic patients had poor prognosis compared with non-anemic patients in HFpEF patients with CKD, but not those without CKD. According to the degree of CKD, anemia affected prognosis in HFpEF patients with mild CKD (45 ≤ eGFR < 60), but not those with moderate to severe CKD (15 ≤ eGFR < 45). Additionally, multivariate analysis revealed that anemia and Hb levels were independent predictors of composite outcomes in HFpEF patients with mild CKD, but not those with moderate to severe CKD. Finally, survival classification and regression tree analysis showed that the optimal Hb levels to predict composite outcomes were 10.7 g/dL in those with mild CKD. Conclusions: Anemia has an impact on prognosis in HFpEF patients, especially among those with mild CKD.

4-Dimensional Flow Cardiovascular Magnetic Resonance Imaging of Changes in Blood Flow Dynamics After Surgery for Discrete Subaortic Stenosis.
Hirokazu Komoriyama, Kiwamu Kamiya, Yuta Kobayashi, Satonori Tsuneta, Takao Konishi, Takuma Sato, Hiroyuki Iwano, Toshiyuki Nagai, Satoru Wakasa, Kohsuke Kudo, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 85, 6, 954, 954, 25 May 2021, [Domestic magazines]
English, Scientific journal

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, May 2021
Japanese

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, May 2021, [International Magazine]
English

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, 23 Apr. 2021, [Domestic magazines]
English, Scientific journal, 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.

JCS/JHFS 2021 Statement on Palliative Care in Cardiovascular Diseases.
Toshihisa Anzai, Takuma Sato, Yoshihiro Fukumoto, Chisato Izumi, Yoshiyuki Kizawa, Masatoshi Koga, Katsuji Nishimura, Mitsuru Ohishi, Akihiro Sakashita, Yasushi Sakata, Tsuyoshi Shiga, Yasuchika Takeishi, Satoshi Yasuda, Kazuhiro Yamamoto, Takahiro Abe, Rie Akaho, Yasuhiro Hamatani, Hayato Hosoda, Naoki Ishimori, Mika Kato, Yoshiharu Kinugasa, Takuro Kubozono, Toshiyuki Nagai, Shogo Oishi, Katsuki Okada, Tatsuhiro Shibata, Atsushi Suzuki, Tsuyoshi Suzuki, Masahito Takagi, Yasuko Takada, Kenkichi Tsuruga, Akiomi Yoshihisa, Dai Yumino, Keiichi Fukuda, Yasuki Kihara, Yoshihiko Saito, Yoshiki Sawa, Hiroyuki Tsutsui, Takeshi Kimura
Circulation journal : official journal of the Japanese Circulation Society, 85, 5, 695, 757, 23 Apr. 2021, [Domestic magazines]
English, Scientific journal

Announcement of the 2021 JCS Meeting Activities (2).
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 85, 5, 573, 575, 23 Apr. 2021, [Domestic magazines]
English, Scientific journal

Association of Low Body Weight with Clinical Outcomes in Elderly Atrial Fibrillation Patients Receiving Apixaban-J-ELD AF Registry Subanalysis.
Takahide Kadosaka, Toshiyuki Nagai, Shinya Suzuki, Ichiro Sakuma, Masaharu Akao, Takeshi Yamashita, Toshihisa Anzai, Ken Okumura
Cardiovascular drugs and therapy, 36, 4, 691, 703, 08 Apr. 2021, [International Magazine]
English, Scientific journal, PURPOSE: Although direct oral anticoagulants are effective and safe in preventing stroke in atrial fibrillation (AF) patients with low body weight, data remain limited in AF patients with extremely low body weight (<50 kg). We aimed to investigate the association of this body weight category with clinical outcomes in elderly AF patients receiving apixaban. METHODS: The J-ELD AF Registry is a large-scale, multicenter prospective observational study of Japanese non-valvular AF patients aged ≥ 75 years taking on-label doses of apixaban. The entire cohort (3025 patients from 110 institutions) was divided into three body weight subgroups: >60 kg (n = 1019, 33.7%), 50-60 kg (n = 1126, 37.2%), and <50 kg (n = 880, 29.1%). RESULTS: The event incidence rates (/100 person years) were 1.69, 1.82, and 1.23 for stroke or systemic embolism (P = 0.60); 1.37, 1.73, and 2.73 for bleeding requiring hospitalization (P = 0.154); 2.02, 2.67, and 4.92 for total death (P = 0.003); and 0.73, 0.95, and 1.23 for cardiovascular death (P = 0.57), respectively. After adjusting for confounders by Cox regression analysis, body weight <50 kg was not an independent risk for stroke or systemic embolism, bleeding requiring hospitalization, total death, or cardiovascular death. CONCLUSIONS: The incidence of events in each body weight group was comparable for stroke or systemic embolism and bleeding requiring hospitalization, and body weight <50 kg might not be an independent risk for death in Japanese non-valvular AF patients aged ≥ 75 years taking on-label doses of apixaban.

拡張機能学再考:beyond E/E' 時相解析に基づく新たな左室充満圧推定指標 僧帽弁輪石灰化例、心房細動例への適用　　　　　　　　　　　　　　　
岩野 弘幸, 村山 迪史, 辻永 真吾, 千葉 泰之, 石坂 傑, 本居 昂, 中鉢 雅大, 加賀 早苗, 安斉 俊久
超音波医学, 48, Suppl., S205, S205, (公社)日本超音波医学会, Apr. 2021
Japanese

SK channel blockade prevents hypoxia-induced ventricular arrhythmias through inhibition of Ca2+/voltage uncoupling in hypertrophied hearts.
Masayuki Takahashi, Hisashi Yokoshiki, Hirofumi Mitsuyama, Masaya Watanabe, Taro Temma, Rui Kamada, Hikaru Hagiwara, Yumi Takahashi, Toshihisa Anzai
American journal of physiology. Heart and circulatory physiology, 320, 4, H1456-H1469, 01 Apr. 2021, [International Magazine]
English, Scientific journal, Ventricular arrhythmia (VA) is the major cause of death in patients with left ventricular (LV) hypertrophy and/or acute ischemia. We hypothesized that apamin, a blocker of small-conductance Ca2+-activated K+ (SK) channels, alters Ca2+ handling and exhibits anti-arrhythmic effects in ventricular myocardium. Spontaneous hypertensive rats were used as a model of LV hypertrophy. A dual optical mapping of membrane potential (Vm) and intracellular calcium (Cai) was performed during global hypoxia (GH) on the Langendorff perfusion system. The majority of pacing-induced VAs during GH were initiated by triggered activities. Pretreatment of apamin (100 nmol/L) significantly inhibited the VA inducibility. Compared with SK channel blockers (apamin and NS8593), non-SK channel blockers (glibenclamide and 4-AP) did not exhibit anti-arrhythmic effects. Apamin prevented not only action potential duration (APD80) shortening (-18.7 [95% confidence interval, -35.2 to -6.05] ms vs. -2.75 [95% CI, -10.45 to 12.65] ms, P = 0.04) but also calcium transient duration (CaTD80) prolongation (14.52 [95% CI, 8.8-20.35] ms vs. 3.85 [95% CI, -3.3 to 12.1] ms, P < 0.01), thereby reducing CaTD80 - APD80, which denotes "Cai/Vm uncoupling" (33.22 [95% CI, 22-48.4] ms vs. 6.6 [95% CI, 0-14.85] ms, P < 0.01). The reduction of Cai/Vm uncoupling was attributable to less prolonged Ca2+ decay constant and suppression of diastolic Cai increase by apamin. The inhibition of VA inducibility and changes in APs/CaTs parameters caused by apamin was negated by the addition of ouabain, an inhibitor of Na+/K+ pump. Apamin attenuates APD shortening, Ca2+ handling abnormalities, and Cai/Vm uncoupling, leading to inhibition of VA occurrence in hypoxic hypertrophied hearts.NEW & NOTEWORTHY We demonstrated that hypoxia-induced ventricular arrhythmias were mainly initiated by Ca2+-loaded triggered activities in hypertrophied hearts. The blockades of small-conductance Ca2+-activated K+ channels, especially "apamin," showed anti-arrhythmic effects by alleviation of not only action potential duration shortening but also Ca2+ handling abnormalities, most notably the "Ca2+/voltage uncoupling."

Rapid Publication and Announcement of the 2021 JCS Meeting Activities.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 85, 4, 331, 332, 25 Mar. 2021, [Domestic magazines]
English, Scientific journal

Characterizing the role of, and physical and emotional burden on caregivers of patients with heart failure: Results from a cross-sectional survey in Japan
Erika Hayashi, Hironobu Mitani, Hiroki Murayama, Toshihisa Anzai, Rachel Studer, Sarah Cotton, James Jackson, Hollie Bailey, Hiroshi Kitagawa, Naotsugu Oyama
Geriatric Nursing, 42, 2, 379, 385, Mosby Inc., 01 Mar. 2021
English, Scientific journal

循環器疾患患者のこころの問題にどう向き合うか?(緩和ケアも含めて) 当院における心不全緩和ケアチームの立ち上げと現状　　　　　　　　　　　　　　　
阿部 隆宏, 佐藤 琢真, 加藤 美香, 笠谷 美鈴, 成田 尚, 福澤 宏之, 片山 真育, 池田 陽子, 小島 尚子, 杉本 由佳, 永井 利幸, 安斉 俊久
日本循環器学会学術集会抄録集, 85回, CS5, 3, (一社)日本循環器学会, Mar. 2021
Japanese

Circulation Journal Awards for the Year 2020.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 85, 3, 225, 234, 25 Feb. 2021, [Domestic magazines]
English, Scientific journal

Takotsubo syndrome in association with acute myocardial infarction: diagnostic caveats and clinical implications. Authors' reply.
Takao Konishi, Naohiro Funayama, Tadashi Yamamoto, Daisuke Hotta, Shinya Tanaka, Toshihisa Anzai
Kardiologia polska, 79, 1, 96, 96, 25 Jan. 2021, [International Magazine]
English

Editorial Statistics and Best Reviewers Award for 2020.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 85, 2, 127, 129, 25 Jan. 2021, [Domestic magazines]
English, Scientific journal

Current practice and effects of intravenous anticoagulant therapy in hospitalized acute heart failure patients with sinus rhythm.
Hiroki Nakano, Yasuhiro Hamatani, Toshiyuki Nagai, Michikazu Nakai, Kunihiro Nishimura, Yoko Sumita, Hisao Ogawa, Toshihisa Anzai
Scientific reports, 11, 1, 1202, 1202, 13 Jan. 2021, [International Magazine]
English, Scientific journal, Although the risk of thromboembolism is increased in heart failure (HF) patients irrespective of atrial fibrillation (AF), especially during the acute decompensated phase, the effects of intravenous anticoagulants for these patients remain unclear. We sought to investigate the current practice and effects of intravenous anticoagulant therapy in acute HF (AHF) patients with sinus rhythm. We analyzed a nationwide prospective cohort from April 2012 to March 2016. We extracted 309,015 AHF adult patients. After application of the exclusion criteria, we divided the 92,573 study population into non-heparin [n = 70,621 (76.3%)] and heparin [n = 21,952 (23.7%)] groups according to the use of intravenous heparin for the first 2 consecutive days after admission. Multivariable logistic regression analyses demonstrated that heparin administration was not associated with in-hospital mortality (OR 0.97, 95% CI 0.91-1.03) and intracranial hemorrhage (OR 1.18, 95% CI 0.78-1.77), while heparin administration was significantly associated with increased incidence of ischemic stroke (OR 1.49, 95% CI 1.29-1.72) and venous thromboembolism (OR 1.62, 95% CI 1.14-2.30). In conclusion, intravenous heparin administration was not associated with favorable in-hospital outcomes in AHF patients with sinus rhythm. Routine additive use of intravenous heparin to initial treatment might not be recommended in AHF patients.

High-Density Lipoprotein Cholesterol and Cardiovascular Events in Patients with Stable Coronary Artery Disease Treated with Statins: An Observation from the REAL-CAD Study.
Kazunori Omote, Isao Yokota, Toshiyuki Nagai, Ichiro Sakuma, Yoshihisa Nakagawa, Kiwamu Kamiya, Hiroshi Iwata, Katsumi Miyauchi, Yukio Ozaki, Kiyoshi Hibi, Takafumi Hiro, Yoshihiro Fukumoto, Hiroyoshi Mori, Seiji Hokimoto, Yasuo Ohashi, Hiroshi Ohtsu, Hisao Ogawa, Hiroyuki Daida, Satoshi Iimuro, Hiroaki Shimokawa, Yasushi Saito, Takeshi Kimura, Masunori Matsuzaki, Ryozo Nagai, Toshihisa Anzai
Journal of atherosclerosis and thrombosis, 29, 1, 50, 68, 09 Jan. 2021, [Domestic magazines]
English, Scientific journal, AIM: The association between high-density lipoprotein cholesterol (HDL-C) level after statin therapy and cardiovascular events in patients with stable coronary artery disease (CAD) remains unclear. Thus, in this study, we sought to determine how HDL-C level after statin therapy is associated with cardiovascular events in stable CAD patients. METHODS: From the REAL-CAD study which had shown the favorable prognostic effect of high-dose pitavastatin in stable CAD patients with low-density lipoprotein cholesterol (LDL-C) ＜120 mg/dL, 9,221 patients with HDL-C data at baseline and 6 months, no occurrence of primary outcome at 6 months, and reported non-adherence for pitavastatin, were examined. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission after 6 months of randomization. Absolute difference and ratio of HDL-C levels were defined as (those at 6 months-at baseline) and (absolute difference/baseline)×100, respectively. RESULTS: During a median follow-up period of 4.0 (IQR 3.2-4.7) years, the primary outcome occurred in 417 (4.5%) patients. The adjusted risk of all HDL-C-related variables (baseline value, 6-month value, absolute, and relative changes) for the primary outcome was not significant (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.91-1.08, HR 1.03, 95% CI 0.94-1.12, HR 1.05, 95% CI 0.98-1.12, and HR 1.08, 95% CI 0.94-1.24, respectively). Furthermore, adjusted HRs of all HDL-C-related variables remained non-significant for the primary outcome regardless of on-treatment LDL-C level at 6 months. CONCLUSIONS: After statin therapy with modestly controlled LDL-C, HDL-C level has little prognostic value in patients with stable CAD.

CORRIGENDUM: Announcement of the 2021 JCS Meeting Activities (2).
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 86, 1, 171, 171, 2021, [Domestic magazines]
English, Scientific journal

右房圧の推定に用いられる超音波指標の精度比較
小野田 愛梨, 村山 迪史, 加賀 早苗, 岡田 一範, 相庭 美穂, 藤澤 亮介, 中鉢 雅大, 横山 しのぶ, 西野 久雄, 西田 睦, 岩野 弘幸, 安斉 俊久
超音波検査技術抄録集, 46, S197, S197, 一般社団法人 日本超音波検査学会, 2021
Japanese

Influence of advanced pulmonary vascular remodeling on accuracy of echocardiographic parameters of left ventricular filling pressure
Yasuyuki Chiba, Hiroyuki Iwano, Sanae Kaga, Mio Shinkawa, Michito Murayama, Hiroshi Ohira, Suguru Ishizaka, Miwa Sarashina, Shingo Tsujinaga, Shinobu Yokoyama, Masahiro Nakabachi, Hisao Nishino, Kazunori Okada, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Pulmonary Circulation, 11, 1, 204589402098372, 204589402098372, SAGE Publications, Jan. 2021
Scientific journal, Evaluation of left ventricular filling pressure plays an important role in the clinical management of pulmonary hypertension. However, the accuracy of echocardiographic parameters for the determination of left ventricular filling pressure in the presence of pulmonary vascular lesions has not been fully addressed. We retrospectively investigated 124 patients with pulmonary hypertension due to pulmonary vascular lesions (noncardiac pulmonary hypertension group) and 113 patients with ischemic heart disease (control group) who underwent right heart catheterization and echocardiography. The noncardiac pulmonary hypertension group was subdivided into less-advanced and advanced groups according to median pulmonary vascular resistance. Pulmonary artery wedge pressure was determined as left ventricular filling pressure. As echocardiographic parameters of left ventricular filling pressure, the ratio of early- (E) to late-diastolic transmitral flow velocity (E/A), ratio of E to early-diastolic mitral annular velocity (E/e′), and left atrial volume index were measured. In the less-advanced noncardiac pulmonary hypertension and control groups, positive correlations were observed between pulmonary artery wedge pressure and late-diastolic transmitral flow velocity ( R = 0.41, P = 0.002 and R = 0.71, P < 0.001, respectively) and left atrial volume index ( R = 0.53, P < 0.001 and R = 0.41, P < 0.001), whereas in the advanced noncardiac pulmonary hypertension group, pulmonary artery wedge pressure was only correlated with left atrial volume index ( R = 0.27, P = 0.032). In the controls, only pulmonary artery wedge pressure determined E (β = 0.48, P < 0.001), whereas both pulmonary artery wedge pressure and pulmonary vascular resistance were independent determinants of E (β = 0.29, P < 0.001 and β = –0.28, P = 0.001, respectively) in the noncardiac pulmonary hypertension group. In conclusion, in the presence of advanced pulmonary vascular lesions, conventional echocardiographic parameters may not accurately reflect left ventricular filling pressure. Elevated pulmonary vascular resistance would lower the E, even when pulmonary artery wedge pressure is elevated, resulting in blunting of echocardiographic parameters for the detection of elevated left ventricular filling pressure.

Acute Myocardial Infarction of the Left Main Coronary Artery Presenting with Cardiogenic Shock and Pulmonary Edema during Noncardiac Surgery.
Sakae Takenaka, Takao Konishi, Tomoya Sato, Atsushi Tada, Takuya Koizumi, Yoshifumi Mizuguchi, Takahide Kadosaka, Ko Motoi, Yuta Kobayashi, Hirokazu Komoriyama, Yoshiya Kato, Miwa Sarashina, Kazunori Omote, Shingo Tsujinaga, Takuma Sato, Rui Kamada, Kiwamu Kamiya, Hiroyuki Iwano, Toshiyuki Nagai, Tatsuya Orimo, Hirofumi Kamachi, Akinobu Taketomi, Toshihisa Anzai
Case reports in cardiology, 2021, 5460816, 5460816, 2021, [International Magazine]
English, Acute myocardial infarction (AMI) caused by severe stenosis of left main coronary artery (LMCA) presenting with cardiogenic shock and pulmonary edema during noncardiac surgery is uncommon, but a catastrophic event. A 77-year-old male with cholangiocarcinoma underwent hepatectomy. During the surgery, he presented with cardiogenic shock, which did not respond to infusion administration or vasopressor. A transesophageal echocardiogram revealed anterior, septal, and lateral severe hypokinesia and impaired left ventricular function. Emergent coronary angiogram showed severe stenosis of LMCA. The patient underwent primary percutaneous coronary intervention (PCI) under the support of intra-aortic balloon pump, followed by extracorporeal membrane oxygenation. The chest roentgenogram showed pulmonary edema. Two days after PCI, he successfully underwent hepatectomy and bile duct resection. Early identification of the cause of hemodynamic instability during noncardiac surgery and invasive strategy are important for minimizing the myocardial injury and improving clinical outcomes in AMI of LMCA.

The effectiveness of drug-coated balloons for two dissimilar calcific lesions assessed by near-infrared spectroscopy intravascular ultrasound and optical coherence tomography.
Takao Konishi, Kohei Saiin, Youji Tamaki, Hiroyuki Natsui, Tomoya Sato, Sakae Takenaka, Atsushi Tada, Yoshifumi Mizuguchi, Yuta Kobayashi, Hirokazu Komoriyama, Yoshiya Kato, Takuma Sato, Rui Kamada, Kiwamu Kamiya, Toshiyuki Nagai, Shinya Tanaka, Toshihisa Anzai
Cardiology journal, 28, 5, 794, 795, 2021, [International Magazine]
English, Scientific journal

Presence and relevance of mid-systolic notching on right ventricular outflow tract flow velocity envelopes in pulmonary hypertension due to heart failure.
Yasuyuki Chiba, Hiroyuki Iwano, Michito Murayama, Sanae Kaga, Ko Motoi, Suguru Ishizaka, Shingo Tsujinaga, Asuka Tanemura, Shinobu Yokoyama, Masahiro Nakabachi, Hisao Nishino, Kazunori Okada, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, 34, 6, 690, 692, 28 Dec. 2020, [International Magazine]
English, Scientific journal

Message From the Editor-in-Chief.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 85, 1, 1, 1, 25 Dec. 2020, [Domestic magazines]
English, Scientific journal

Lower left ventricular ejection fraction and higher serum angiotensin-converting enzyme activity are associated with histopathological diagnosis by endomyocardial biopsy in patients with cardiac sarcoidosis.
Hirokazu Komoriyama, Kazunori Omote, Toshiyuki Nagai, Yoshiya Kato, Nobutaka Nagano, Kazuhiro Koyanagawa, Kiwamu Kamiya, Takao Konishi, Takuma Sato, Yuta Kobayashi, Shingo Tsujinaga, Hiroyuki Iwano, Kengo Kusano, Satoshi Yasuda, Hisao Ogawa, Hatsue Ishibashi-Ueda, Toshihisa Anzai
International journal of cardiology, 321, 113, 117, 15 Dec. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: The histopathological diagnosis of cardiac sarcoidosis (CS) is challenging because of sampling error in endomyocardial biopsy (EMB) and the determinants of positive EMB are unclear. Reduced left ventricular ejection fraction (LVEF) is a simple parameter of the extent of myocardial damage, and higher serum angiotensin-converting enzyme (ACE) activity would indicate the spread of disease activity in CS patients. Thus, we sought to examine whether these parameters are related to the histopathological diagnosis of CS by EMB. METHODS: A total of 94 consecutive clinically diagnosed CS patients between August 1986 and March 2019 who were admitted to two academic hospitals were examined. We determined EMB as positive if non-caseating epithelioid granulomas were confirmed in the myocardial tissue. Patients were divided into two groups according to positive (n = 37) and negative (n = 57) EMB. We assessed the relationship between LVEF, serum ACE activity and positive EMB. RESULTS: Multivariable analysis revealed that both LVEF and serum ACE were independently associated with positive EMB (OR 0.83, 95% CI 0.70-0.99; OR 1.39, 95% CI 1.02-1.90, respectively). Moreover, patients with both lower LVEF (<37%, median) and higher ACE activity (≥13.5 IU/L, median) had the highest frequency of positive EMB (p = .003). The combination of lower LVEF and higher serum ACE showed better specificity (91.2%) and positive predictive value (73.7%) than either LVEF or serum ACE alone for positive EMB. CONCLUSIONS: Lower LVEF and higher serum ACE activity were associated with positive EMB, suggesting that these parameters might be useful for predicting positive EMB in CS patients.

A propensity score matching analysis for cardio metabolic risk of antipsychotics in patients with schizophrenia using Japanese claims data.
Ichiro Kusumi, Sachie Inoue, Kenji Baba, Tadashi Nosaka, Toshihisa Anzai
BMC psychiatry, 20, 1, 584, 584, 09 Dec. 2020, [International Magazine]
English, Scientific journal, BACKGROUND: The aim of this study was to evaluate the cardio-metabolic risk in schizophrenia patients treated by atypical antipsychotic drugs compared with that in those treated without atypical antipsychotic drugs using a nationwide insurance claims database and medical examination database in Japan. METHODS: Eligible patients were defined as those meeting the following two criteria: (i) A diagnosis of schizophrenia (ICD-10 code: F20) was made between 1 January 2005 and 31 December 2017, with data available for at least 6 months before the diagnosis was made (index month), and (ii) health check-up data were available within ±3 months of the index month. The primary endpoint was changes in cardio-metabolic risk based on the Suita score at 1 year, and the secondary endpoints were changes in medical examination data related to cardio-metabolic risk (total cholesterol [TC], triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, body mass index [BMI], and hemoglobin A1c) at 1 year. The primary endpoint was evaluated by multivariate analysis, with the cumulative chlorpromazine equivalent amount and the baseline Suita score added as covariates. RESULTS: One-hundred eighty five pairs of propensity score (PS)-matched patients were evaluated. Patients receiving atypical antipsychotic drugs exhibited a greater change in the Suita score and a risk of coronary heart disease based on the Suita score of 0.530 and 0.098%, respectively, than patients not receiving atypical antipsychotic drugs, but there was no significant difference (p = 0.412 and 0.610). The significant changes in TC and BMI were determined as 6.525 mg/dL and 0.380 kg/m2 greater, respectively, in patients treated with atypical antipsychotic drugs (p = 0.037 and 0.011). CONCLUSIONS: There were no significant increases in changes in the Suita score at 1 year by treatment with atypical antipsychotic drugs compared with treatment without atypical antipsychotic drugs. However, the TC and BMI were significantly higher in patients treated with atypical antipsychotic drugs.

Refractory Ventricular Tachycardia in a Patient With a Left Ventricular Assist Device Successfully Treated With Stellate Ganglion Phototherapy.
Tomoya Sato, Rui Kamada, Takuya Koizumi, Sakae Takenaka, Atsushi Tada, Shingo Tsujinaga, Takao Konishi, Takuma Sato, Masaya Watanabe, Toshiyuki Nagai, Toshihisa Anzai
The Canadian journal of cardiology, 36, 12, 1977.e1-1977.e3, Dec. 2020, [Peer-reviewed], [International Magazine]
English, Neuraxial modulation therapies, such as stellate ganglion block, thoracic epidural anaesthesia, and cardiac sympathetic denervation, are effective for ventricular arrhythmias. However, these treatments can increase the risk of bleeding and infection. In this case report, stellate ganglion phototherapy was safely and effectively performed for refractory ventricular tachycardias in a patient with a history of left ventricular assist device implantation. Stellate ganglion phototherapy may have the potential to treat refractory ventricular arrhythmias as an additive therapy or bridge therapy.

Study protocol for prospect trial to elucidate the utility of echocardiography-based cardiac output in acute heart failure (PREDICT).
Hiroyuki Iwano, Kentaro Shibayama, Takeshi Kitai, Kenya Kusunose, Tetsuari Onishi, Hidekazu Tanaka, Toshihisa Anzai
Journal of echocardiography, 18, 4, 235, 239, Dec. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: Early worsening heart failure (WHF), defined as worsening of symptoms and signs of heart failure requiring intensification of medical or mechanical therapy during an admission for acute decompensated heart failure (ADHF), has recently been recognized as a risk of morbidity or mortality after the discharge. Although echocardiographic parameters of left ventricular (LV) output has been shown to be associated with long-term outcome in heart failure patients, its predictive value for early WHF has not been elucidated. METHODS: Prospect trial to Elucidate the utility of EchocarDiography-based Cardiac output in acute heart failure (PREDICT) is a multicenter, nonrandomized, prospective observational study to test the predictive value of echocardiographic LV output parameters for early WHF in ADHF patients. We will enroll patients admitted to 16 participating hospitals due to ADHF who did not receive positive inotropic agents as an initial therapy. Primary outcome will be set at early WHF defined as need for initiation of positive inotropic agents within 7 days after the admission. Predictive accuracy will be compared between Doppler echocardiographic LV output (stroke distance, stroke volume index, and cardiac index) and low perfusion findings assessed by physical examination. RESULTS: N/A. CONCLUSIONS: The PREDICT is expected to provide large data set to test the predictive value of echocardiographic LV output for early WHF in ADHF patients.

Activation of invariant natural killer T cells by alpha-galactosylceramide ameliorates doxorubicin-induced cardiotoxicity in mice.
Yoshikuni Obata, Naoki Ishimori, Akimichi Saito, Shintaro Kinugawa, Takashi Yokota, Shingo Takada, Ippei Nakano, Naoya Kakutani, Katsuma Yamanashi, Toshihisa Anzai
European journal of preventive cardiology, 27, 19, 2358, 2361, Dec. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal

18F-FDG uptake of the right ventricle is an important predictor of histopathologic diagnosis by endomyocardial biopsy in patients with cardiac sarcoidosis.
Kazunori Omote, Masanao Naya, Kazuhiro Koyanagawa, Tadao Aikawa, Osamu Manabe, Toshiyuki Nagai, Kiwamu Kamiya, Yoshiya Kato, Hirokazu Komoriyama, Masato Kuzume, Nagara Tamaki, Toshihisa Anzai
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 27, 6, 2135, 2143, Dec. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: The aim of this study was to determine whether right ventricle (RV) 18F-fluorodeoxyglucose (FDG) uptake can predict positive findings of endomyocardial biopsy (EMB) in patients with cardiac sarcoidosis (CS). METHODS: 70 consecutive patients with clinically diagnosed CS who had undergone FDG PET were registered in the present study. Patients without EMB (n = 42) were excluded. Ultimately, 28 patients were studied. EMB samples were obtained from the RV septum. We evaluated the FDG uptake on six segments (RV, left ventricle anterior, septal, lateral, inferior, and apex). RESULTS: Positive EMB was found in six patients (21%). Patients were divided into two groups according to positive (n = 12 [43%]) or negative (n = 16 [57%]) RV FDG uptake. Patients with positive RV FDG uptake had a significantly higher frequency of positive EMB than those without (42% vs. 6%, P = 0.024). On the other hand, there was no EMB-predictive value for the FDG uptakes in the other five segments, the cardiac metabolic volume, total lesion glycolysis, left ventricular ejection fraction, or any electrocardiogram findings. CONCLUSIONS: FDG uptake of the RV but no other heart segment was associated with positive EMB in CS patients. The presence of RV FDG uptake could improve the rate of positive EMB up to 42% in patients with CS.

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, 28 Nov. 2020, [Domestic magazines]
English, Scientific journal, 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.

Message From the Editor-in-Chief.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 84, 12, 2127, 2128, 25 Nov. 2020, [Domestic magazines]
English, Scientific journal

Burden of Heart Failure on Patient Daily Life and Patient-Physician Discordance in Disease Management - Results From a Cross-Sectional Survey in Japan.
Tomoko Hayashi, Yohei Morita, Hironobu Mitani, Hiroki Murayama, Toshihisa Anzai, Rachel Studer, Sarah Cotton, James Jackson, Hollie Bailey, Hiroshi Kitagawa, Naotsugu Oyama
Circulation reports, 2, 12, 722, 729, 17 Nov. 2020, [Domestic magazines]
English, Scientific journal, Background: We investigated the impact of heart failure (HF) on daily life and satisfaction with current HF medication from the patient perspective in a real-world study in Japan. Methods and Results: A cross-sectional survey of 154 HF patients treated by 58 cardiologists was conducted in Japan using patient self-completed questionnaires about their daily life and satisfaction with HF medication, as well as patient record forms completed by their physicians capturing corresponding data. The mean age of patients was 72.7 years. The proportion of patients within New York Heart Association Class I, II, III, and IV was 39%, 44%, 16%, and 1%, respectively. Symptoms reported by patients included dyspnea when active (46%), nocturia (43%), anxiety (18%), and depression (6%). There was a discordance between physician- and patient-reported symptoms, especially for nocturia and inability to sleep. The most frequent lifestyle recommendation from physicians was 'reduce salt/sodium intake', but only 51% of patients receiving this recommendation followed the advice. In all, 44% of patients reported dissatisfaction with their current medication; according to the patients, 27% reported no discussion with their physicians about their prescribed medication, while physicians reported the opposite. Conclusions: HF negatively impacts patient daily life. There is discordance between patients and physicians in symptom reporting, lifestyle modification advice and adherence, and reported medication decision making. Gaps in patient-physician communication exist.

Independent and incremental prognostic value of semiquantitative measures of tricuspid regurgitation severity in heart failure with preserved ejection fraction.
Tomonari Harada, Masaru Obokata, Kazunori Omote, Hiroyuki Iwano, Takahiro Ikoma, Kenya Okada, Kuniko Yoshida, Toshimitsu Kato, Koji Kurosawa, Toshiyuki Nagai, Kazuaki Negishi, Toshihisa Anzai, Masahiko Kurabayashi
European heart journal cardiovascular Imaging, 07 Nov. 2020, [International Magazine]
English, Scientific journal, AIMS: This study sought to determine the independent and incremental prognostic value of semiquantitative measures of tricuspid regurgitation (TR) severity over right heart remodelling and pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: Echocardiography was performed on 311 HFpEF patients. TR severity was defined by the semiquantitative measures [i.e. vena contracta width (VCW) and jet area] and by the guideline-based integrated qualitative approach (absent, mild, moderate, or severe). All-cause mortality or heart failure hospitalization occurred in 101 patients over a 2.1-year median follow-up. There was a continuous association between TR severity and the composite outcome with a hazard ratio (HR) of 1.17 per 1 mm increase of VCW [95% confidence interval (CI) 1.08-1.26, P < 0.0001]. Compared with patients with the lowest VCW category (≤1 mm), RV-adjusted HRs for the outcome were 1.99 (95% CI 1.05-3.77), 2.63 (95% CI 1.16-5.95), and 5.00 (95% CI 1.60-15.7) for 1-3, 3-7, and ≥7 mm VCW categories, respectively. TR severity as defined by the guideline-based approach showed a similarly graded association, but it was no longer significant in models including PH. In contrast, VCW remained independently and incrementally associated with the outcome after adjusting for established prognostic factors, as well as RV diameter and PH (fully adjusted HR 1.14 per 1 mm, 95% CI 1.02-1.27, P = 0.02; χ2 58.8 vs. 51.5, P = 0.03). CONCLUSION: The current data highlight the potential value of the semiquantitative measures of TR severity for the risk stratification in patients with HFpEF.

肺静脈血流速度波形を用いたリザーバ期の左房硬さの非侵襲的評価法の検討　　　　　　　　　　　　　　　
阿部 剛大, 岡田 一範, 加賀 早苗, 政氏 伸夫, 三神 大世, 村山 迪史, 中鉢 雅大, 辻永 真吾, 岩野 弘幸, 安斉 俊久
超音波医学, 47, Suppl., S246, S246, (公社)日本超音波医学会, Nov. 2020
Japanese

房室弁開放時相差の視覚的評価に基づいたスコアリングによる左室充満圧推定と予後予測　　　　　　　　　　　　　　　
村山 迪史, 岩野 弘幸, 辻永 真吾, 西野 久雄, 中鉢 雅大, 横山 しのぶ, 西田 睦, 渋谷 斉, 加賀 早苗, 安斉 俊久
超音波医学, 47, Suppl., S165, S165, (公社)日本超音波医学会, Nov. 2020
Japanese

収縮期の右房容量負荷が三尖弁輪収縮期移動距離と右室駆出率との関係に及ぼす影響　　　　　　　　　　　　　　　
村山 迪史, 加賀 早苗, 岡田 一範, 三神 大世, 中鉢 雅大, 横山 しのぶ, 西野 久雄, 西田 睦, 岩野 弘幸, 安斉 俊久
超音波医学, 47, Suppl., S222, S222, (公社)日本超音波医学会, Nov. 2020
Japanese

経カテーテル的大動脈弁置換術による左室機能の変化と左室外的仕事量との関連　　　　　　　　　　　　　　　
辻永 真吾, 岩野 弘幸, 石坂 傑, 千葉 泰之, 更科 美羽, 中鉢 雅大, 神谷 究, 永井 利幸, 安斉 俊久
超音波医学, 47, Suppl., S208, S208, (公社)日本超音波医学会, Nov. 2020
Japanese

Placebo-Controlled, Double-Blind Study of Empagliflozin (EMPA) and Implantable Cardioverter-Defibrillator (EMPA-ICD) in Patients with Type 2 Diabetes (T2DM): Rationale and Design.
Shinya Fujiki, Kenichi Iijima, Masaaki Okabe, Shinichi Niwano, Kenichi Tsujita, Shigeto Naito, Kenji Ando, Kengo Kusano, Ritsushi Kato, Junichi Nitta, Tetsuji Miura, Takeshi Mitsuhashi, Kazuomi Kario, Yusuke Kondo, Masaki Ieda, Nobuhisa Hagiwara, Toyoaki Murohara, Kazuyoshi Takahashi, Hirofumi Tomita, Yasuchika Takeishi, Toshihisa Anzai, Wataru Shimizu, Masafumi Watanabe, Yoshihiro Morino, Takeshi Kato, Hiroshi Tada, Yoshihisa Nakagawa, Masafumi Yano, Koji Maemura, Takeshi Kimura, Hisako Yoshida, Keiko Ota, Takahiro Tanaka, Nobutaka Kitamura, Koichi Node, Yoshifusa Aizawa, Ippei Shimizu, Daisuke Izumi, Kazuyuki Ozaki, Tohru Minamino
Diabetes therapy : research, treatment and education of diabetes and related disorders, 11, 11, 2739, 2755, Nov. 2020, [International Magazine]
English, Scientific journal, INTRODUCTION: Type 2 diabetes (T2DM) is associated with cardiovascular death, including sudden cardiac death due to arrhythmias. Patients with an implantable cardioverter-defibrillator (ICD) are also at high risk of developing a clinically significant ventricular arrhythmia. It has been reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors can reduce cardiovascular deaths; however, the physiological mechanisms of this remain unclear. It is, however, well known that SGLT2 inhibitors increase blood ketone bodies, which have been suggested to have sympatho-suppressive effects. Empagliflozin (EMPA) is an SGLT2 inhibitor. The current clinical trial titled "Placebo-controlled, double-blind study of empagliflozin (EMPA) and implantable cardioverter-defibrillator (EMPA-ICD) in patients with type 2 diabetes (T2DM)" was designed to investigate the antiarrhythmic effects of EMPA. METHODS: The EMPA-ICD study is a prospective, multicenter, placebo-controlled, double-blind, randomized, investigator-initiated clinical trial currently in progress. A total of 210 patients with T2DM (hemoglobin A1c 6.5-10.0%) will be randomized (1:1) to receive once-daily placebo or EMPA, 10 mg, for 24 weeks. The primary endpoint is the number of clinically significant ventricular arrhythmias for 24 weeks before and 24 weeks after study drug administration, as documented by the ICD. The secondary endpoints of the study are the change from baseline concentrations in blood ketone and catecholamine 24 weeks after drug treatment. CONCLUSION: The EMPA-ICD study is the first clinical trial to assess the effect of an SGLT2 inhibitor on clinically significant ventricular arrhythmias in patients with T2DM and an ICD. TRIAL REGISTRATION: Unique trial number, jRCTs031180120 ( https://jrct.niph.go.jp/latest-detail/jRCTs031180120 ).

Functional significance of intra-left ventricular vortices on energy efficiency in normal, dilated, and hypertrophied hearts.
Miwa Sarashina-Motoi, Hiroyuki Iwano, Ko Motoi, Suguru Ishizaka, Yasuyuki Chiba, Shingo Tsujinaga, Michito Murayama, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Kazunori Okada, Sanae Kaga, Toshihisa Anzai
Journal of clinical ultrasound : JCU, 49, 4, 358, 367, 24 Oct. 2020, [International Magazine]
English, Scientific journal, PURPOSE: To investigate the influence of changes in vortices within the left ventricle (LV) on energy efficiency (EE) in normal and diseased hearts. METHODS: We performed vector flow mapping echocardiography in 36 normal participants (N), 36 patients with dilated cardiomyopathy (D), and 36 patients with LV hypertrophy (H). The circulation of the main anterior vortex was measured as a parameter of vortex strength. Energy loss (EL) was measured for one cardiac cycle, and EE was calculated as EL divided by stroke work (SW), which represents the loss of kinetic energy per unit of LV external work. RESULTS: Circulation increased in the order of N, H, and D (N: 15 ± 4, D: 19 ± 8, H: 17 ± 6 × 10-3 m2 /s; analysis of variance [ANOVA] P < .01). Conversely, EE increased in the order of N, D, and H (N: 0.22 ± 0.07, D: 0.26 ± 0.16, H: 0.30 ± 0.16 10-5 J/mm Hg mL m s; ANOVA P = .04), suggesting worst EE in group H. We found a positive correlation between circulation and SW only in group N, and positive correlation between circulation and EE only in diseased groups (D: R = 0.55, P < .01; H: R = 0.44, P < .01). Multivariable analyses revealed that circulation was the independent determinant of EE in groups D and H. CONCLUSIONS: Enhanced vortices could be associated with effective increase in LV external work in normal hearts. Conversely, they were associated with loss of EE without an optimal increase in external work in failing hearts, regardless of the LV morphology.

Greetings From the New Editor-in-Chief.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 84, 11, 1889, 1889, 23 Oct. 2020, [Domestic magazines]
English, Scientific journal

Mechanism of Early-Diastolic Mitral Regurgitation.
Michito Murayama, Hiroyuki Iwano, Miwa Sarashina, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 84, 11, 2036, 2036, 23 Oct. 2020, [Domestic magazines]
English, Scientific journal

Message From the Editor-in-Chief.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 84, 11, 1890, 1894, 23 Oct. 2020, [Domestic magazines]
English, Scientific journal

Derivation and Validation of Clinical Prediction Models for Rapid Risk Stratification for Time-Sensitive Management for Acute Heart Failure.
Yasuyuki Shiraishi, Shun Kohsaka, Takayuki Abe, Toshiyuki Nagai, Ayumi Goda, Yosuke Nishihata, Yuji Nagatomo, Mike Saji, Yuichi Toyosaki, Makoto Takei, Takeshi Kitai, Takashi Kohno, Keiichi Fukuda, Yuya Matsue, Toshihisa Anzai, Tsutomu Yoshikawa
Journal of clinical medicine, 9, 11, 23 Oct. 2020, [International Magazine]
English, Scientific journal, Early and rapid risk stratification of patients with acute heart failure (AHF) is crucial for appropriate patient triage and outcome improvements. We aimed to develop an easy-to-use, in-hospital mortality risk prediction tool based on data collected from AHF patients at their initial presentation. Consecutive patients' data pertaining to 2006-2017 were extracted from the West Tokyo Heart Failure (WET-HF) and National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure (NaDEF) registries (n = 4351). Risk model development involved stepwise logistic regression analysis and prospective validation using data pertaining to 2014-2015 in the Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure Syndrome (REALITY-AHF) (n = 1682). The final model included data describing six in-hospital mortality risk predictors, namely, age, systolic blood pressure, blood urea nitrogen, serum sodium, albumin, and natriuretic peptide (SOB-ASAP score), available at the time of initial triage. The model showed excellent discrimination (c-statistic = 0.82) and good agreement between predicted and observed mortality rates. The model enabled the stratification of the mortality rates across sixths (from 14.5% to <1%). When assigned a point for each associated factor, the integer score's discrimination was similar (c-statistic = 0.82) with good calibration across the patients with various risk profiles. The models' performance was retained in the independent validation dataset. Promptly determining in-hospital mortality risks is achievable in the first few hours of presentation; they correlate strongly with mortality among AHF patients, potentially facilitating clinical decision-making.

Acute anterior myocardial infarction complicated by takotsubo syndrome: the value of multimodality imaging.
Takao Konishi, Naohiro Funayama, Tadashi Yamamoto, Daisuke Hotta, Shinya Tanaka, Toshihisa Anzai
Kardiologia polska, 78, 10, 1055, 1056, 23 Oct. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal

A Rare Combination: Cardiac Myxoma and Aortic Stenosis.
Takao Konishi, Daisuke Hotta, Shinya Tanaka, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 60, 6, 961, 962, 14 Oct. 2020, [Domestic magazines]
English, Scientific journal

Abnormal FDG uptake predicting the instability of thoracic aortic aneurysms.
Yasuyuki Chiba, Kiwamu Kamiya, Tadao Aikawa, Hiroyuki Iwano, Toshiyuki Nagai, Takahiro Ishigaki, Yasushige Shingu, Ai Shimizu, Yoshiro Matsui, Toshihisa Anzai
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 27, 5, 1841, 1843, Oct. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal

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, Oct. 2020
Japanese

【循環器疾患のPrecision Medicine】臨床 心不全個別化医療
永井 利幸, 安斉 俊久
Cardiac Practice, 31, 1, 32, 36, (株)メディカルレビュー社, Oct. 2020
Japanese

Rapid-rate nonsustained ventricular tachycardias in high-risk dilated cardiomyopathy patients.
Wei-Chieh Lee, Masaya Watanabe, Hisashi Yokoshiki, Taro Temma, Rui Kamada, Masayuki Takahashi, Hikaru Hagiwara, Yumi Takahashi, Toshihisa Anzai
Pacing and clinical electrophysiology : PACE, 43, 10, 1086, 1095, Oct. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIMS: Nonsustained ventricular tachycardia (NSVT) occurs frequently in patients with dilated cardiomyopathy (DCM), especially in high-risk patients. The role of rapid-rate NSVT (RR-NSVT) documented by an implantable cardioverter-defibrillator (ICD) in DCM patients has not been fully explored. This study aimed to determine the relationship between RR-NSVT and the occurrence of ventricular tachyarrhythmias (VTAs) in DCM patients with ICD. METHODS: From December 2000 to December 2017, 136 DCM patients received ICD or cardiac resynchronization therapy defibrillator (CRT-D) implantation for primary or secondary prevention of VTAs. Based on the occurrence of documented RR-NSVT, patients were classified into RR-NSVT (-) or RR-NSVT (+) groups. RESULT: During the median follow-up of 4.5 years, 50.0% (68/136) patients experienced ≥1 episode, and 25.0% (34/136) patients experienced ≥3 episodes of RR-NSVT. Event-free survival for VTAs was significantly higher in the RR-NSVT (-) group, whereas those for heart failure admission and cardiovascular mortality were comparable between groups. In the multivariate Cox regression analysis, any RR-NSVT showed a positive association with the occurrence of VTAs (hazard ratio: 5.087; 95% confidence interval: 2.374-10.900; P < .001). In RR-NSVT (+) patients, a cluster (≥3 times/6 months) and frequent pattern (≥3 runs/day) of RR-NSVT were observed in 42.6% (29/68) and 30.9% (21/68) patients, respectively, who showed further increased incidence of VTAs. CONCLUSION: In DCM patients with ICD/CRT-D, 50.0% patients experienced at least one episode of RR-NSVT. RR-NSVT documentation showed a positive association with subsequent occurrence of VTAs, suggesting the importance of constructive arrhythmia management for patients with RR-NSVT.

Type 2 diabetes is an independent predictor of lowered peak aerobic capacity in heart failure patients with non-reduced or reduced left ventricular ejection fraction.
Takahiro Abe, Takashi Yokota, Arata Fukushima, Naoya Kakutani, Takashi Katayama, Ryosuke Shirakawa, Satoshi Maekawa, Hideo Nambu, Yoshikuni Obata, Katsuma Yamanashi, Ippei Nakano, Shingo Takada, Isao Yokota, Koichi Okita, Shintaro Kinugawa, Toshihisa Anzai
Cardiovascular diabetology, 19, 1, 142, 142, 19 Sep. 2020, [International Magazine]
English, Scientific journal, BACKGROUND: Although type 2 diabetes mellitus (T2DM) is one of the most frequent comorbidities in patients with chronic heart failure (CHF), the effects of T2DM on the exercise capacity of CHF patients are fully unknown. Here, we tested the hypothesis that the coexistence of T2DM lowers CHF patients' peak aerobic capacity. METHODS: We retrospectively analyzed the cases of 275 Japanese CHF patients with non-reduced ejection fraction (left ventricular ejection fraction [LVEF] ≥ 40%) or reduced EF (LVEF < 40%) who underwent cardiopulmonary exercise testing. We divided them into diabetic and nondiabetic groups in each CHF cohort. RESULTS: The mean peak oxygen uptake (VO2) value was 16.87 mL/kg/min in the non-reduced LVEF cohort and 15.52 mL/kg/min in the reduced LVEF cohort. The peak VO2 was lower in the diabetics versus the nondiabetics in the non-reduced LVEF cohort with the mean difference (95% confidence interval [95% CI]) of - 0.93 (- 1.82 to - 0.04) mL/kg/min and in the reduced LVEF cohort with the mean difference of - 1.05 (- 1.96 to - 0.15) mL/kg/min, after adjustment for age-squared, gender, anemia, renal function, LVEF, and log B-type natriuretic peptide (BNP). The adjusted VO2 at anaerobic threshold (AT), a submaximal aerobic capacity, was also decreased in the diabetic patients with both non-reduced and reduced LVEFs. Intriguingly, the diabetic patients had a lower adjusted peak O2 pulse than the nondiabetic patients in the reduced LVEF cohort, but not in the non-reduced LVEF cohort. A multivariate analysis showed that the presence of T2DM was an independent predictor of lowered peak VO2 in CHF patients with non-reduced LVEF and those with reduced LVEF. CONCLUSIONS: T2DM was associated with lowered peak VO2 in CHF patients with non-reduced or reduced LVEF. The presence of T2DM has a negative impact on CHF patients' exercise capacity, and the degree of impact is partly dependent on their LV systolic function.

Acute Gastric Dilation after Catheter Ablation.
Tomoya Sato, Takao Konishi, Rui Kamada, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 59, 18, 2341, 2341, 15 Sep. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Cardiac involvement with anti-mitochondrial antibody-positive myositis mimicking cardiac sarcoidosis.
Takahide Kadosaka, Shingo Tsujinaga, Hiroyuki Iwano, Kiwamu Kamiya, Azusa Nagai, Yoshifumi Mizuguchi, Ko Motoi, Kazunori Omote, Toshiyuki Nagai, Ichiro Yabe, Toshihisa Anzai
ESC heart failure, 11 Sep. 2020, [International Magazine]
English, Anti-mitochondrial antibody (AMA)-positive myositis is an atypical inflammatory myopathy characterized by chronic progressive respiratory muscle weakness, muscular atrophy, and cardiac involvement. Arrhythmias, cardiomyopathy, and myocarditis have been reported as cardiac manifestations. Herein, we present the first report of a patient diagnosed with having AMA-positive myositis with cardiac involvement mimicking cardiac sarcoidosis.

Myocardial T1-mapping and Extracellular Volume Quantification in Patients and Putative Carriers of Muscular Dystrophy: Early Experience.
Kazuhiro Koyanagawa, Yuta Kobayashi, Tadao Aikawa, Atsuhito Takeda, Hideaki Shiraishi, Satonori Tsuneta, Noriko Oyama-Manabe, Hiroyuki Iwano, Toshiyuki Nagai, Toshihisa Anzai
Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine, 20, 3, 320, 324, 07 Sep. 2020, [Domestic magazines]
English, Scientific journal, To assess myocardial fibrosis associated with muscular dystrophy, T1-mapping and extracellular volume fraction (ECV) quantification was prospectively performed using cardiovascular MR (CMR) imaging in 6 male patients with muscular dystrophy and 5 female putative carriers of Duchenne or Becker muscular dystrophy. Five patients and all putative carriers had an elevated ECV (>29.5% for men and >35.2% for women), suggesting that ECV has a potential to detect diffuse fibrotic changes in patients and putative carriers of muscular dystrophy.

Usefulness of Liver Magnetic Resonance Elastography for Estimating Right-Atrial Pressure in Heart Failure Patients.
Yoshiya Kato, Toshiyuki Nagai, Noriko Oyama-Manabe, Satonori Tsuneta, Michikazu Nakai, Yuta Kobayashi, Hirokazu Komoriyama, Kazunori Omote, Shingo Tsujinaga, Takuma Sato, Takao Konishi, Kiwamu Kamiya, Hiroyuki Iwano, Toshihisa Anzai
JACC. Cardiovascular imaging, 13, 9, 2050, 2052, Sep. 2020, [Peer-reviewed], [International Magazine]
English

Reversible Cancer Therapeutics-related Cardiac Dysfunction Complicating Intra-cardiac Thrombi.
Shingo Tsujinaga, Hiroyuki Iwano, Tomohiro Oshino, Takahide Kadosaka, Yoshifumi Mizuguchi, Ko Motoi, Yasuyuki Chiba, Taro Koya, Taro Temma, Kiwamu Kamiya, Arata Fukushima, Takuya Koizumi, Tomoya Sato, Sakae Takenaka, Atsushi Tada, Suguru Ishizaka, Miwa Sarashina, Kazunori Omote, Rui Kamada, Takao Konishi, Takuma Sato, Toshiyuki Nagai, Hiroko Yamashita, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 59, 17, 2155, 2160, 01 Sep. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Epirubicin-based chemotherapy carries a risk of inducing heart failure, although the frequency is rare. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, has recently been widely used in patients with recurrent breast cancer as a first-line chemotherapeutic agent. Heart failure or arterial thromboembolism has been reported as a rare cardiovascular complication of bevacizumab. We herein report a breast cancer patient with reversible cancer therapeutics-related cardiac dysfunction associated with bevacizumab and epirubicin complicating intracardiac thrombi in the left atrium and left ventricle. This case underscores the importance of tailored medical planning according to the individual status in patients receiving anti-cancer therapies.

Outer Retinal Abnormalities in a Patient with Danon Disease.
Ayaka Hasegawa, Kousuke Noda, Akio Fujiya, Kiriko Hirooka, Toshihisa Anzai, Susumu Ishida
Retinal cases & brief reports, 31 Aug. 2020, [International Magazine]
English, Scientific journal, PURPOSE: To report outer retinal abnormalities evaluated using high-resolution imaging modalities in a patient with Danon disease. METHODS: Case report. RESULTS: A 26-year-old woman, diagnosed with Danon disease based on genetic testing, was referred to our department for further evaluation of ocular findings. Her best-corrected visual acuity was 20/20, and color vision was normal. Fundus examination revealed pigmentary changes consisting of mottled depigmentation and pigmentation in the peripheral retina of both eyes. Spectral-domain optical coherence tomography (SD-OCT) revealed disruptions of the ellipsoid and interdigitation zones, irregularity of the retinal pigment epithelium (RPE), and hyperreflectivity of the outer nuclear layer. In addition, an adaptive optics retinal camera demonstrated the ambiguous macular cone mosaic pattern. CONCLUSION: Danon disease is caused by a primary deficiency in lysosomal associated membrane protein 2 (LAMP-2), an important constituent of the lysosomal membrane that plays a crucial role in the process of autophagy. It is possible that the findings of SD-OCT and adaptive optics retinal camera are early changes associated with the accumulation of autophagosomes and/or phagosomes due to LAMP-2 dysfunction in the photoreceptors, eventually followed by outer retinal degeneration, such as thinning of both the photoreceptor and RPE layers at the fovea.

JCS 2020 Guideline on Diagnosis and Treatment of Cardiac Amyloidosis.
Hiroaki Kitaoka, Chisato Izumi, Yasuhiro Izumiya, Takayuki Inomata, Mitsuharu Ueda, Toru Kubo, Jun Koyama, Motoaki Sano, Yoshiki Sekijima, Nobuhiro Tahara, Nobuhiro Tsukada, Kenichi Tsujita, Hiroyuki Tsutsui, Takeshi Tomita, Masashi Amano, Jin Endo, Atsushi Okada, Seitaro Oda, Seiji Takashio, Yuichi Baba, Yohei Misumi, Masahide Yazaki, Toshihisa Anzai, Yukio Ando, Mitsuaki Isobe, Takeshi Kimura, Keiichi Fukuda
Circulation journal : official journal of the Japanese Circulation Society, 84, 9, 1610, 1671, 25 Aug. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Enhanced Echo Intensity of Skeletal Muscle Is Associated With Exercise Intolerance in Patients With Heart Failure.
Ippei Nakano, Hiroaki Hori, Arata Fukushima, Takashi Yokota, Shintaro Kinugawa, Shingo Takada, Katsuma Yamanashi, Yoshikuni Obata, Yasuyuki Kitaura, Naoya Kakutani, Takahiro Abe, Toshihisa Anzai
Journal of cardiac failure, 26, 8, 685, 693, Aug. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Skeletal muscle is quantitatively and qualitatively impaired in patients with heart failure (HF), which is closely linked to lowered exercise capacity. Ultrasonography (US) for skeletal muscle has emerged as a useful, noninvasive tool to evaluate muscle quality and quantity. Here we investigated whether muscle quality based on US-derived echo intensity (EI) is associated with exercise capacity in patients with HF. METHODS AND RESULTS: Fifty-eight patients with HF (61 ± 12 years) and 28 control subjects (58 ± 14 years) were studied. The quadriceps femoris echo intensity (QEI) was significantly higher and the quadriceps femoris muscle thickness (QMT) was significantly lower in the patients with HF than the controls (88.3 ± 13.4 vs 81.1 ± 7.5, P= .010; 5.21 ± 1.10 vs 6.54 ±1.34 cm, P< .001, respectively). By univariate analysis, QEI was significantly correlated with age, peak oxygen uptake (VO2), and New York Heart Association class in the HF group. A multivariable analysis revealed that the QEI was independently associated with peak VO2 after adjustment for age, gender, body mass index, and QMT: β-coefficient = -11.80, 95%CI (-20.73, -2.86), P= .011. CONCLUSION: Enhanced EI in skeletal muscle was independently associated with lowered exercise capacity in HF. The measurement of EI is low-cost, easily accessible, and suitable for assessment of HF-related alterations in skeletal muscle quality.

Prognostic impact of moderate mitral regurgitation on hospitalized heart failure patients with preserved ejection fraction: A report from the JASPER registry.
Masayoshi Oikawa, Akiomi Yoshihisa, Yu Sato, Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Kazuhiro Yamamoto, Yasuchika Takeishi, Toshihisa Anzai
Heart and vessels, 35, 8, 1087, 1094, Aug. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, A growing body of evidence suggests that mitral regurgitation (MR) is associated with higher mortality in heart failure patients with reduced ejection fraction. However, prognostic impact of MR on heart failure patients with preserved ejection fraction (HFpEF) has not been fully examined. The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese hospitalized HFpEF patients with LVEF ≥ 50%. Severe valvular heart disease was excluded from this cohort. We divided the consecutive 341 patients into two groups based on the severity of MR at discharge: no or mild MR group (n = 317) and moderate MR group (n = 24). Compared with no or mild MR group, moderate MR group showed larger left ventricular end-diastolic diameter (52 [48-59] vs. 46 [42-50] mm, P < 0.001), left ventricular systolic diameter (35 [30-37] vs. 29 [26-34] mm, P = 0.006), left atrial diameter (49 [46-56] vs. 45 [40-50] mm, P < 0.001), and higher tricuspid regurgitation peak gradient (33 [25-40] vs. 27 [21-33] mmHg, P = 0.012). In contrast, levels of plasma B-type natriuretic peptide and left ventricular ejection fraction were comparable between the two groups. In the follow-up period (median 738 days), there were 57 all-cause deaths. In the Kaplan-Meier analysis, all-cause mortality was higher in moderate MR group than in no or mild MR group (log-rank P = 0.023). In the Cox proportional hazard analysis, moderate MR at discharge was a predictor of all-cause mortality (hazard ratio 2.256, 95% confidence interval 1.035-4.917, P = 0.041). Moderate MR at discharge is associated with adverse prognosis in hospitalized patients with HFpEF.

Significance and prognostic impact of v wave on pulmonary artery pressure in patients with heart failure: beyond the wedge pressure.
Hiroyuki Iwano, Shinobu Yokoyama, Kiwamu Kamiya, Toshiyuki Nagai, Shingo Tsujinaga, Miwa Sarashina, Suguru Ishizaka, Yasuyuki Chiba, Masahiro Nakabachi, Hisao Nishino, Michito Murayama, Kazunori Okada, Sanae Kaga, Toshihisa Anzai
Heart and vessels, 35, 8, 1079, 1086, Aug. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: A v wave on pulmonary artery wedge (PAW) pressure sometimes augments and appears on pulmonary artery (PA) pressure wave in patients with heart failure (HF). However, the significance of PA v wave in HF remains to be elucidated. METHODS: We retrospectively analyzed pressure waveforms in 61 HF patients (left ventricular ejection fraction 35 ± 15%). On the PAW and PA pressure waveforms, mean pressure as well as peak and amplitude of v waves (ampPAWv and ampPAv, respectively) were measured. Occurrence of worsening HF and cardiac death was recorded for 2 years after the catheterization. RESULTS: The ampPAWv did not correlate with ampPAv. When the patients were divided into 4 groups: I (high-ampPAWv/high-ampPAv), II (high-ampPAWv/low-ampPAv), III (low-ampPAWv/high-ampPAv), and IV (low-ampPAWv/low-ampPAv), the prevalence of group III was low (I: 13, II: 17, III: 4, IV: 27). Mean pressures of PAW and PA were similarly elevated in groups I and II. Cardiac index was lowest (I: 2.0 ± 0.4, II: 2.8 ± 0.6, III: 2.2 ± 0.2, IV: 2.4 ± 0.6 L/min/m2, ANOVA P < 0.01, P < 0.01 for I vs II) and tricuspid annular plane systolic excursion / systolic PA pressure was impaired (I: 0.27 ± 0.07, II: 0.48 ± 0.22, III: 0.59 ± 0.35, IV: 0.68 ± 0.35 mm/mmHg, ANOVA P < 0.01) in group I. During the follow-up, 13 events were observed. Kaplan-Meier analysis showed that patients in group I were at highest risk of cardiac events. CONCLUSIONS: PA v was observed mainly in patients with augmented PAW v wave and decreased cardiac index, suggesting an advanced stage of HF. Moreover, augmented PAv was associated with worse outcome in HF patients.

Prognostic value of base excess as indicator of acid-base balance in acute heart failure.
Hiroki Nakano, Toshiyuki Nagai, Yasuyuki Honda, Satoshi Honda, Naotsugu Iwakami, Chisa Matsumoto, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Hisao Ogawa, Satoshi Yasuda, Taishiro Chikamori, Toshihisa Anzai
European heart journal. Acute cardiovascular care, 9, 5, 399, 405, Aug. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Acid-base balance can change as a result of pulmonary oedema and low tissue perfusion in acute heart failure patients. However, its long-term prognostic significance remains to be clarified. METHODS: We prospectively examined a cohort of 472 consecutive acute heart failure patients who underwent arterial blood gas analysis on admission between January 2013 and May 2016. Acidaemia, alkalaemia and normal range of base excess were defined as pH <7.38, >7.42 and -2 to 2 mEq/L, respectively. The primary outcome was all-cause death. RESULTS: During a median follow-up period of 714 days, 101 patients died. Although there was no difference in mortality among patients with acidaemia, normal pH and alkalaemia (p = 0.92), patients with high base excess had the highest mortality compared with others. Multivariable Cox proportional hazard models revealed that high base excess was an independent determinant of mortality (hazard ratio 1.83, 95% confidence interval 1.08-3.13 (high versus normal base excess), hazard ratio 0.81, 95% confidence interval 0.47-1.41 (low versus normal base excess)), even after adjustment for significant prognostic covariates. Furthermore, regarding mortality stratified by base excess and carbon dioxide partial pressure (pCO2), patients with high base excess (>2.1 mEq/L) and high pCO2 (>40 mmHg) had the highest mortality compared with others. CONCLUSIONS: High base excess, but not low base excess, on admission was associated with long-term mortality in acute heart failure patients, indicating the importance of evaluating acid-base balance on admission by base excess for stratifying the risk of mortality in patients with acute heart failure.

Elevated admission urinary N-acetyl-β-D-glucosamidase level is associated with worse long-term clinical outcomes in patients with acute heart failure.
Sayaka Funabashi, Kazunori Omote, Toshiyuki Nagai, Yasuyuki Honda, Hiroki Nakano, Satoshi Honda, Naotsugu Iwakami, Yasuhiro Hamatani, Michikazu Nakai, Kunihiro Nishimura, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
European heart journal. Acute cardiovascular care, 9, 5, 429, 436, Aug. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: The prognostic significance of urinary N-acetyl-β-D-glucosamidase in acute heart failure has not been fully elucidated. Accordingly, this study investigated whether urinary N-acetyl-β-D-glucosamidase could be associated with subsequent adverse events in acute heart failure patients. METHODS: We studied 708 consecutive acute heart failure patients who had accessible N-acetyl-β-D-glucosamidase data on admission from the National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure registry. We assessed the relationship between the admission N-acetyl-β-D-glucosamidase level and the combined endpoint of all-cause death and worsening heart failure. Worsening heart failure was defined as worsening symptoms and signs of heart failure requiring intensification of intravenous therapy such as diuretics, vasodilators and inotropes or initiation of mechanical support after stabilisation with initial treatment during hospitalisation, or readmission due to heart failure after discharge. RESULTS: During a median follow-up period of 763 (interquartile range 431-1028) days, higher urinary N-acetyl-β-D-glucosamidase was significantly related to increased events of all-cause death and worsening heart failure. In addition, patients with higher urinary N-acetyl-β-D-glucosamidase and lower estimated glomerular filtration rate on admission had the worst clinical outcomes. In multivariable Cox regression, urinary N-acetyl-β-D-glucosamidase on admission was independently associated with adverse events (hazard ratio 1.19, 95% confidence interval 1.04-1.35) even after adjustment by covariates including the baseline estimated glomerular filtration rate. CONCLUSIONS: Higher urinary N-acetyl-β-D-glucosamidase level on admission was independently associated with worse clinical outcomes. Our findings indicate the potential value of assessing urinary N-acetyl-β-D-glucosamidase on admission for further risk stratification in patients with acute heart failure.

Quality indicators of palliative care for acute cardiovascular diseases.
Atsushi Mizuno, Mitsunori Miyashita, Takashi Kohno, Yasuharu Tokuda, Shuhei Fujimoto, Masato Nakamura, Morimasa Takayama, Koichiro Niwa, Terunobu Fukuda, Shinichi Ishimatsu, Satomi Kinoshita, Shogo Oishi, Hiroki Mochizuki, Akemi Utsunomiya, Yasuko Takada, Ryota Ochiai, Toshiaki Mochizuki, Ken Nagao, Saran Yoshida, Akitoshi Hayashi, Ryuichi Sekine, Toshihisa Anzai
Journal of cardiology, 76, 2, 177, 183, Aug. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Although recent attention to palliative care for patients with cardiovascular diseases has been increasing, there are no specific recommendations on detailed palliative care practices. We proceed on a discussion of the appropriateness and applicability of potential quality indicators for acute cardiovascular diseases according to our previous systematic review. METHODS: We created a multidisciplinary panel of 20 team members and 7 external validation clinicians composed of clinical cardiologists, a nutritionist, a physiotherapist, a clinical psychologist, a critical and emergent care specialist, a catheterization specialist, a primary care specialist, a palliative care specialist, and nurses. After crafting potential indicators, we performed a Delphi rating, ranging from "1 = minimum" to "9 = maximum". The criterion for the adoption of candidate indicators was set at a total mean score of seven or more. Finally, we subcategorized these indicators into several domains by using exploratory factor analysis. RESULTS: Sixteen of the panel members (80%) were men (age, 49.5 ± 13.7 years old). Among the initial 32 indicators, consensus was initially reached on total 23 indicators (71.8%), which were then summarized into 21 measures by selecting relatively feasible time variations. The major domains were "symptom palliation" and "supporting the decision-making process". Factor analysis could not find optimal model. Narratively-developed seven sub-categories included "presence of palliative care team", "patient-family relationship", "multidisciplinary team approach", "policy of approaching patients", "symptom screening and management", "presence of ethical review board", "collecting and providing information for decision-maker", and "determination of treatment strategy and the sharing of the care team's decision". CONCLUSION: In this study we developed 21 quality indicators, which were categorized into 2 major domains and 7 sub-categories. These indicators might be useful for many healthcare providers in the initiation and enhancement of palliative care practices for acute cardiovascular diseases in Japan.

Phosphoglyceride crystal deposition disease as a rare tumour after cardiac surgery.
Tomoya Sato, Takao Konishi, Satoru Wakasa, Noriko Oyama-Manabe, Toshihisa Anzai
European heart journal, 41, 27, 2596, 2596, 14 Jul. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal

Prevalence, Determinants, and Prognostic Significance of Hospital Acquired Pneumonia in Patients with Acute Heart Failure.
Atsushi Tada, Kazunori Omote, Toshiyuki Nagai, Yasuyuki Honda, Hiroki Nakano, Satoshi Honda, Naotsugu Iwakami, Yasuhiro Hamatani, Michikazu Nakai, Kunihiro Nishimura, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
Journal of clinical medicine, 9, 7, 13 Jul. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, The prognostic impact of hospital-acquired pneumonia (HAP) in acute heart failure (AHF) patients have not been fully elucidated. We evaluated 776 consecutive hospitalized AHF patients. The primary in-hospital outcomes were all-cause death and worsening heart failure (WHF), while the outcome following discharge was all-cause death. The clinical diagnosis of HAP was based on clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Patients with HAP had a significantly higher incidence of in-hospital death (12% vs. 1%, p < 0.001), WHF during the hospitalization (28% vs. 7%, p < 0.001), and longer length of hospital stay (p = 0.003) than those without. Among patients who survived at discharge, during a median follow-up period of 741 (interquartile range 422-1000) days, the incidence of all-cause death was significantly higher in patients with HAP than in those without (p < 0.001). In the multivariable Cox regression, HAP development was independently associated with all-cause death after discharge (HR [hazard ratio] 1.86, 95%CI [confidence interval] 1.08-3.19). Furthermore, older age (OR [odds ratio] 1.04, 95%CI 1.01-1.08), male sex (OR 2.21, 95%CI 1.14-4.28), and higher serum white blood cell count (OR 1.18, 95%CI 1.09-1.29) and serum C-reactive protein (OR 1.08, 95%CI 1.01-1.06) were independently associated with HAP development. In hospitalized patients with AHF, HAP development was associated with worse clinical outcomes, suggesting the importance of prevention and early screening for HAP.

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, Elsevier BV, Jul. 2020
Scientific journal

Radiofrequency catheter ablation of a sporadically occurring ventricular arrhythmia originating from the right ventricular outflow tract: A novel arrhythmia induction strategy involving atrial fibrillation provocation.
Taro Koya, Taro Temma, Masaya Watanabe, Rui Kamada, Toshiyuki Nagai, Toshihisa Anzai
HeartRhythm case reports, 6, 7, 411, 414, Jul. 2020, [Peer-reviewed], [International Magazine]
English

Invasive Cardiac Lipoma Complicating Visceral Inversion
Takahide Kadosaka, Shingo Tsujinaga, Hiroyuki Iwano, Noriko Oyama-Manabe, Toshihisa Anzai
JACC: Case Reports, 2, 10, 1570, 1571, Elsevier BV, Jul. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, We report a case of cardiac lipoma with intramyocardial invasion complicated by visceral inversion, which, to the best of our knowledge, has not been reported before. Multimodality imaging played an important role in differential diagnosis and determination of the management strategy. (Level of Difficulty: Advanced.).

Detailed visualization of the right and left ventricular, left atrial, and epicardial involvement of cardiac sarcoidosis with novel semiconductor PET/CT.
Osamu Manabe, Noriko Oyama-Manabe, Toshiyuki Nagai, Sho Furuya, Toshihisa Anzai
European journal of nuclear medicine and molecular imaging, 47, 7, 1773, 1774, Jul. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal

Experience of morphine therapy for refractory dyspnea as palliative care in advanced heart failure patients.
Juri Kawaguchi, Yasuhiro Hamatani, Atsushi Hirayama, Kunihiro Nishimura, Eri Nakai, Emi Nakamura, Michi Miyata, Yukie Kawano, Yasuko Takada, Yuta Anchi, Sayaka Funabashi, Kensuke Kuroda, Michiyo Azechi, Hiroyuki Takahama, Toshihisa Anzai, Satoshi Yasuda, Hiroaki Kitaoka, Chisato Izumi
Journal of cardiology, 75, 6, 682, 688, Jun. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: In the field of palliative care, morphine is known to be effective for alleviating dyspnea in cancer patients. However, little is known regarding the safety and efficacy of morphine therapy for refractory dyspnea as palliative care in advanced heart failure (HF) patients. METHODS: We retrospectively reviewed consecutive advanced HF patients who were referred to the Palliative Care Team at our institution and administered morphine for refractory dyspnea during hospitalization between September 2013 and December 2018. We investigated the details of morphine usage, vital signs, an 11-point quantitative symptom scale, and adverse events at baseline, 24 h, and 72 h after the start of treatment. RESULTS: Morphine was administered for refractory dyspnea in 43 advanced HF patients [mean age: 73.5 years, male: 28 (65%), New York Heart Association functional class IV: 43 (100%), median left ventricular ejection fraction: 25%, median B-type natriuretic peptide level: 927 pg/ml, concurrent intravenous inotrope: 33 (77%)]. Median initial dose of morphine was 5 mg/day in both oral and intravenous administration and median duration of administration was 5 days. Significant decreases in an 11-point quantitative symptom scale [7 (5, 9) vs. 2 (1, 6); p <  0.01, (data available in 8 patients)] and respiratory rate (22.2 ± 6.1 vs. 19.7 ± 5.2 breaths per minute; p < 0.01) were observed 24 h after the start of morphine administration. Meanwhile, oxygen saturation, blood pressure, and heart rate were not significantly altered after treatment (NS). Common adverse events were delirium (18%) and constipation (8%); however, no lethal adverse event definitely related to morphine therapy occurred during treatment. CONCLUSIONS: This single-center retrospective study revealed the clinical practice of morphine therapy and suggested that morphine therapy might be feasible for refractory dyspnea as palliative care in advanced HF patients.

What is this image? 2020: Image 6 result : A case of ventricular apical aneurysm with suspected IgG4-related arteritis on steroid therapy.
Kazuhiro Koyanagawa, Masanao Naya, Osamu Manabe, Toshihisa Anzai
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 27, 3, 719, 722, Jun. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal

Branched-chain amino acid supplementation ameliorates angiotensin II-induced skeletal muscle atrophy.
Katsuma Yamanashi, Shintaro Kinugawa, Arata Fukushima, Naoya Kakutani, Shingo Takada, Yoshikuni Obata, Ippei Nakano, Takashi Yokota, Yasuyuki Kitaura, Yoshiharu Shimomura, Toshihisa Anzai
Life sciences, 250, 117593, 117593, 01 Jun. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIMS: Sarcopenia is characterized by muscle mass and strength loss and reduced physical activity. Branched-chain amino acids (BCAAs) were recently described as an activator of protein synthesis via mammalian target of rapamycin (mTOR) signaling for muscle atrophy. In cardiovascular diseases, excessive activation of the renin-angiotensin system may induce an imbalance of protein synthesis and degradation, and this plays a crucial role in muscle atrophy. We investigated the effects of BCAAs on angiotensin II (Ang II)-induced muscle atrophy in mice. MATERIALS AND METHODS: We administered Ang II (1000 ng/kg/min) or vehicle to 10-12-week-old male C57BL/6J mice via subcutaneous osmotic minipumps for 4 weeks with or without BCAA supplementation (3% BCAA in tap water). KEY FINDINGS: The skeletal muscle weight/tibial length and cross-sectional area were smaller in the Ang II mice than the vehicle mice; these changes were induced by an imbalance of protein synthesis and degradation signaling such as Akt/mTOR and MuRF-1/Atrogin-1. Compared to the Ang II mice, the mTOR signaling was significantly activated and Ang II-induced muscle atrophy was ameliorated in the Ang II + BCAA mice, and this attenuated the reduction of exercise capacity. Notably, the decrease of muscle weight/tibial length in the fast-twitch dominant muscles (e.g., the extensor digitorum longus) was significantly ameliorated compared to that in the slow-twitch dominant muscles (e.g., soleus). Histologically, the effect of BCAA was larger in fast-twitch than slow-twitch fibers, which may be related to the difference in BCAA catabolism. SIGNIFICANCE: BCAA supplementation could contribute to the prevention of skeletal muscle atrophy induced by Ang II.

Sex differences in Japanese patients with ruptured aortic aneurysms.
Tetsuo Yamaguchi, Michikazu Nakai, Yoko Sumita, Kunihiro Nishimura, Toshihiro Nozato, Takashi Ashikaga, Toshiyuki Nagai, Toshihisa Anzai, Yasushi Sakata, Hitoshi Ogino
Journal of vascular surgery, 71, 6, 1907, 1912, Jun. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, OBJECTIVE: This study aimed to assess the sex differences in clinical presentation and outcomes of Japanese patients with ruptured aortic aneurysm (rAA) using a large nationwide claims-based database in Japan. METHODS: We identified patients hospitalized in certified teaching hospitals in Japan with rAA between April 1, 2012, and March 31, 2015. Patients' characteristics and in-hospital outcomes were compared between men and women. The Barthel index was used for evaluating functional status at discharge by examining the ability to perform basic daily activities. RESULTS: Of 7086 eligible patients, 32.3% (2291/7086) were women. Women were older than men (81.9 years vs 76.1 years; P < .001), had higher prevalence of coma at admission (33.2% vs 25.2%; P < .001), and were less likely to undergo emergency operation including endovascular aneurysm repair (35.7% vs 51.1%; P < .001). The unadjusted mortality rate (62.5% vs 52.0%; P < .001) and Barthel index at discharge (78.7 vs 86.1; P < .001) were significantly worse in women than in men. However, multilevel mixed-effect logistic regression analyses showed that female sex itself was not an independent predictor for in-hospital death (odds ratio [OR], 0.90; 95% confidence interval [CI], 0.78-1.04; P = .17). Older age, coma at admission, and vasopressor use were detected as independent predictors for in-hospital death. The same results were confirmed for each rupture site. Stratified analyses showed that older women (threshold, 80 years; OR, 0.81; 95% CI, 0.66-0.98; P = .028) and those who underwent emergency operation (OR, 0.75; 95% CI, 0.61-0.93; P = .009) showed significantly better outcomes than men. CONCLUSIONS: In a univariate analysis, female patients with rAA showed worse mortality than men because of their older age, more severe clinical presentation, and low emergency operation rate. However, after adjustment for covariates, female sex itself was not associated with increased mortality.

Cardiac sarcoidosis mimicking myocardial infarction: a comprehensive evaluation using computed tomography and positron emission tomography.
Tadao Aikawa, Kazuhiro Koyanagawa, Noriko Oyama-Manabe, Toshihisa Anzai
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 27, 3, 1066, 1067, Jun. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal

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 (Tokyo, Japan), 59, 10, 1277, 1281, 15 May 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, A 23-year-old man had progressive muscle weakness and Emery-Dreifuss muscular dystrophy (EDMD) due to a LMNA (lamin A/C) mutation. Congestive heart failure diagnosed at 19 years of age. Maximal drug treatment/cardiac resynchronization failed to improve the cardiac function. He was therefore hospitalized due to heart failure. Despite extracorporeal membrane oxygenation, he developed severe right heart dysfunction and died (multiple organ failure). A cardiac lesion's presence determines the prognosis of EDMD. While there are many arrhythmia reports, few reports on heart failure (particularly severe heart failure requiring cardiac transplantation) have been published. Right heart function monitoring and early ventricular-assist device use plus right heart support considering heart transplantation are important.

Inhibition of xanthine oxidase in the acute phase of myocardial infarction prevents skeletal muscle abnormalities and exercise intolerance.
Hideo Nambu, Shingo Takada, Satoshi Maekawa, Junichi Matsumoto, Naoya Kakutani, Takaaki Furihata, Ryosuke Shirakawa, Takashi Katayama, Takayuki Nakajima, Katsuma Yamanashi, Yoshikuni Obata, Ippei Nakano, Masaya Tsuda, Akimichi Saito, Arata Fukushima, Takashi Yokota, Junko Nio-Kobayashi, Hironobu Yasui, Kei Higashikawa, Yuji Kuge, Toshihisa Anzai, Hisataka Sabe, Shintaro Kinugawa
Cardiovascular research, 117, 3, 805, 819, 13 May 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIMS: Exercise intolerance in patients with heart failure (HF) is partly attributed to skeletal muscle abnormalities. We have shown that reactive oxygen species (ROS) play a crucial role in skeletal muscle abnormalities, but the pathogenic mechanism remains unclear. Xanthine oxidase (XO) is reported to be an important mediator of ROS overproduction in ischemic tissue. Here we tested the hypothesis that skeletal muscle abnormalities in HF are initially caused by XO-derived ROS and are prevented by the inhibition of their production. METHODS AND RESULTS: Myocardial infarction (MI) was induced in male C57BL/6J mice, which eventually led to HF, and a sham operation was performed in control mice. The time course of XO-derived ROS production in mouse skeletal muscle post-MI was first analyzed. XO-derived ROS production was significantly increased in MI mice from days 1 to 3 postsurgery (acute phase), whereas it did not differ between the MI and sham groups from 7 to 28 days (chronic phase). Second, mice were divided into three groups: sham+vehicle (Sham+Veh), MI+vehicle (MI+Veh), and MI+febuxostat (an XO inhibitor, 5 mg/kg body weight/day; MI+Feb). Febuxostat or vehicle was administered at 1 hr and 24 hr before surgery, and once-daily on days 1-7 postsurgery. On day 28 postsurgery, exercise capacity and mitochondrial respiration in skeletal muscle fibers were significantly decreased in MI+Veh compared with Sham+Veh mice. An increase in damaged mitochondria in MI+Veh compared with Sham+Veh mice was also observed. The wet weight and cross-sectional area of slow muscle fibers (higher XO-derived ROS) was reduced via the downregulation of protein synthesis-associated mTOR-p70S6K signaling in MI+Veh compared with Sham+Veh mice. These impairments were ameliorated in MI+Feb mice, in association with a reduction of XO-derived ROS production, without affecting cardiac function. CONCLUSIONS: XO inhibition during the acute phase post-MI can prevent skeletal muscle abnormalities and exercise intolerance in mice with HF. A TRANSLATIONAL PERSPECTIVE: We clearly demonstrated that febuxostat, an inhibitor of xanthine oxidase (XO), prevents exercise intolerance and skeletal muscle abnormalities (mitochondrial dysfunction and atrophy) via the suppression of XO-derived reactive oxygen species increase during hypoxia (e.g., myocardial infarction [MI]) in skeletal muscle during the early phase of heart failure (HF) model mouse. Our results shed light on the pathogenic mechanism of skeletal muscle abnormalities in HF after MI. The use of XO inhibitors requires consideration of the time course of XO activity. Our results indicate that the timing of administration is very important to achieve maximum beneficial effects when using XO inhibitors.

Heart Failure With Preserved Ejection Fraction vs. Reduced Ejection Fraction ― Mechanisms of Ventilatory Inefficiency During Exercise in Heart Failure ―
Shingo Tsujinaga, Hiroyuki Iwano, Yasuyuki Chiba, Suguru Ishizaka, Miwa Sarashina, Michito Murayama, Masahiro Nakabachi, Hisao Nishino, Shinobu Yokoyama, Kazunori Okada, Sanae Kaga, Toshihisa Anzai
Circulation Reports, 2, 5, 271, 279, Japanese Circulation Society, 08 May 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Background: Ventilatory inefficiency during exercise assessed using the lowest minute ventilation/carbon dioxide production (V̇E/V̇CO2) ratio was recently proven to be a strong prognostic marker of heart failure (HF) regardless of left ventricular ejection fraction (LVEF). Its physiological background, however, has not been elucidated. Methods and Results: Fifty-seven HF patients underwent cardiopulmonary exercise testing and exercise-stress echocardiography. The lowest V̇E/V̇CO2 ratio was assessed on respiratory gas analysis. Echocardiography was obtained at rest and at peak exercise. LVEF was measured using the method of disks. Cardiac output (CO) and the ratio of transmitral early filling velocity (E) to early diastolic tissue velocity (e') were calculated using the Doppler method. HF patients were divided into preserved EF (HFpEF) and reduced EF (HFrEF) using the LVEF cut-off 40% at rest. Twenty-four patients were classified as HFpEF and 33 as HFrEF. In HFpEF, age (r=0.58), CO (r=-0.44), e' (r=-0.48) and E/e' (r=0.45) during exercise correlated with the lowest V̇E/V̇CO2 ratio (P<0.05 for all). In contrast, in HFrEF, age (r=0.47) and CO (r=-0.54) during exercise, but not e' and E/e', correlated with the lowest V̇E/V̇CO2 ratio. Conclusions: Loss of CO augmentation was associated with ventilatory inefficiency in HF regardless of LVEF, although lung congestion determined ventilatory efficiency only in HFpEF.

Procedural Volume and Outcomes After Percutaneous Coronary Intervention for Unprotected Left Main Coronary Artery Disease-Report From the National Clinical Data (J-PCI Registry).
Tadao Aikawa, Kyohei Yamaji, Toshiyuki Nagai, Shun Kohsaka, Kiwamu Kamiya, Kazunori Omote, Taku Inohara, Yohei Numasawa, Kenichi Tsujita, Tetsuya Amano, Yuji Ikari, Toshihisa Anzai
Journal of the American Heart Association, 9, 9, e015404, 05 May 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Background There is a limited evidence base to support the volume-outcome relationship in patients undergoing percutaneous coronary intervention (PCI) for unprotected left main coronary artery disease (UPLMD). This study aimed to evaluate the relationship between institutional and operator volume and in-hospital outcomes in patients undergoing PCI for unprotected left main coronary artery disease. Methods and Results We analyzed characteristics and clinical outcomes of 24 320 patients undergoing PCI for unprotected left main coronary artery disease at 1102 hospitals by 7244 operators using data from the Japanese nationwide J-PCI Registry (National PCI Data Registry) between January 2014 and December 2017. We classified institutions and operators into quartiles based on the mean annual volume of PCI. A generalized linear mixed-effects model was used to evaluate the association between institutional and operator PCI volume and in-hospital outcomes. Among the 24 320 patients, 4027 (16.6%), 6147 (25.3%), and 14 146 (58.2%) presented with ST-segment-elevation myocardial infarction, non-ST-segment-elevation acute coronary syndrome, and stable ischemic heart disease; their crude in-hospital mortality was 15%, 3.1%, and 0.3%, respectively. Compared with patients in the lowest quartile of institutional volume (1-216 PCIs/y), the adjusted odds ratio of in-hospital death in patients in the second (217-323 PCIs/y), third (324-487 PCIs/y), and fourth (488-3015 PCIs/y) quartile of institutional volume was 0.75 (95% CI, 0.51-1.10; P=0.14), 0.87 (95% CI, 0.57-1.34; P=0.54), and 0.51 (95% CI, 0.30-0.86; P=0.01), respectively. These findings were consistent in rates of in-hospital death or any complication. Conversely, operator PCI volume was not significantly associated with in-hospital outcomes. Conclusions Institutional rather than operator-based PCI volume was associated with better in-hospital outcomes in patients undergoing PCI for unprotected left main coronary artery disease.

Optimal sampling in derivation studies was associated with improved discrimination in external validation for heart failure prognostic models.
Naotsugu Iwakami, Toshiyuki Nagai, Toshiaki A Furukawa, Aran Tajika, Akira Onishi, Kunihiro Nishimura, Soshiro Ogata, Michikazu Nakai, Misa Takegami, Hiroki Nakano, Yohei Kawasaki, Ana Carolina Alba, Gordon Henry Guyatt, Yasuyuki Shiraishi, Shun Kohsaka, Takashi Kohno, Ayumi Goda, Atsushi Mizuno, Tsutomu Yoshikawa, Toshihisa Anzai
Journal of clinical epidemiology, 121, 71, 80, May 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, OBJECTIVES: The objective of the study was to identify determinants of external validity of prognostic models. STUDY DESIGN AND SETTING: We systematically searched for studies reporting prognostic models of heart failure (HF) and examined their performance for predicting 30-day death in a cohort of consecutive 3,452 acute HF patients. We applied published critical appraisal tools and examined whether bias or other characteristics of original derivation studies determined model performance. RESULTS: We identified 224 models from 6,354 eligible studies. The mean c-statistic in the cohort was 0.64 (standard deviation, 0.07). In univariable analyses, only optimal sampling assessed by an adequate and valid description of the sampling frame and recruitment details to collect the population of interest (total score range: 0-2, higher scores indicating lower risk of bias) was associated with high performance (standardized β = 0.25, 95% CI: 0.12 to 0.38, P < 0.001). It was still significant after adjustment for relevant study characteristics, such as data source, scale of study, stage of illness, and study year (standardized β = 0.24, 95% CI: 0.07 to 0.40, P = 0.01). CONCLUSION: Optimal sampling representing the gap between the population of interest and the studied population in derivation studies was a key determinant of external validity of HF prognostic models.

Impact of Hospital Practice Factors on Mortality in Patients Hospitalized for Heart Failure in Japan - An Analysis of a Large Number of Health Records From a Nationwide Claims-Based Database, the JROAD-DPC.
Hidetaka Kaku, Kouta Funakoshi, Tomomi Ide, Takeo Fujino, Shouji Matsushima, Kisho Ohtani, Taiki Higo, Michikazu Nakai, Yoko Sumita, Kunihiro Nishimura, Yoshihiro Miyamoto, Toshihisa Anzai, Hiroyuki Tsutsui
Circulation journal : official journal of the Japanese Circulation Society, 84, 5, 742, 753, 24 Apr. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: An inverse relationship exists between hospital case volume and mortality in patients with heart failure (HF). However, hospital performance factors associated with mortality in HF patients have not been examined. We aimed to identify these using exploratory factor analysis and assess the relationship between these factors and 7-day, 30-day, and in-hospital mortality among HF patients in Japan.Methods and Results:We analyzed the records of 198,861 patients admitted to 683 certified hospitals of the Japanese Circulation Society between 2012 and 2014. Records were obtained from the nationwide database of the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC). Using exploratory factor analysis, 90 hospital survey items were grouped into 5 factors, according to their collinearity: "Interventional cardiology", "Cardiovascular surgery", "Pediatric cardiology", "Electrophysiology" and "Cardiac rehabilitation". Multivariable logistic regression analysis was performed to determine the association between these factors and mortality. The 30-day mortality was 8.0%. Multivariable logistic regression analysis showed the "Pediatric cardiology" (odds ratio (OR) 0.677, 95% confidence interval [CI]: 0.628-0.729, P<0.0001), "Electrophysiology" (OR 0.876, 95% CI: 0.832-0.923, P<0.0001), and "Cardiac rehabilitation" (OR 0.832, 95% CI: 0.792-0.873, P<0.0001) factors were associated with lower mortality. In contrast, "Interventional cardiology" (OR 1.167, 95% CI: 1.070-1.272, P<0.0001) was associated with higher mortality. CONCLUSIONS: Hospital factors, including various cardiovascular therapeutic practices, may be associated with the early death of HF patients.

Difference in the prevalence of subclinical left ventricular impairment among left ventricular geometric pattern in a community-based population.
Takuya Hasegawa, Masanori Asakura, Hiroshi Asanuma, Makoto Amaki, Hiroyuki Takahama, Yasuo Sugano, Hideaki Kanzaki, Satoshi Yasuda, Toshihisa Anzai, Chisato Izumi, Masafumi Kitakaze
Journal of cardiology, 75, 4, 439, 446, Apr. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Left ventricular (LV) hypertrophy is reported to cause LV diastolic dysfunction. This study aimed to examine the prevalence of LV diastolic dysfunction in each group categorized by the geometric pattern of LV hypertrophy in a community-based population. METHODS: We studied 1260 community-dwelling subjects who experienced no symptoms of obvious heart disease (461 men, 799 women) and who participated in annual health check-ups in a rural Japanese community. The subjects were divided into 4 groups according to LV mass index and relative wall thickness: normal geometry, concentric remodeling, eccentric hypertrophy, and concentric hypertrophy. We investigated the prevalence of LV diastolic dysfunction in the overall and stratified population by LV geometric pattern. LV diastolic function was determined by 3 echocardiographic parameters of LV diastolic function: early diastolic myocardial velocity, the ratio of early diastolic mitral inflow velocity and myocardial velocity, and indexed left atrial dimension. LV diastolic dysfunction was defined as the presence of abnormal values in more than 2 of 3 echocardiographic parameters. RESULTS: The prevalence of LV diastolic dysfunction was higher in the categories with more severe LV hypertrophy. However, LV mass index, rather than relative wall thickness, was a significant determinant of LV diastolic dysfunction, after adjustment for comorbidities. In addition, 71 (10%) out of 740 subjects with normal LV geometric pattern had LV diastolic dysfunction even without obvious LV geometric change. CONCLUSIONS: The prevalence of LV diastolic dysfunction was higher in the subjects with more severe LV hypertrophy in a community-based population. Subclinical LV diastolic dysfunction without obvious LV geometric change should be noted and its clinical impact should be elucidated.

Prognostic Value of 18F-FDG PET Using Texture Analysis in Cardiac Sarcoidosis.
Osamu Manabe, Kazuhiro Koyanagawa, Kenji Hirata, Noriko Oyama-Manabe, Hiroshi Ohira, Tadao Aikawa, Sho Furuya, Masanao Naya, Ichizo Tsujino, Yuuki Tomiyama, Yuka Otaki, Toshihisa Anzai, Nagara Tamaki
JACC. Cardiovascular imaging, 13, 4, 1096, 1097, Apr. 2020, [Peer-reviewed], [International Magazine]
English

Development and Practical Test of Quality Indicators for Palliative Care in Patients With Chronic Heart Failure.
Yasuhiro Hamatani, Yasuko Takada, Yoshihiro Miyamoto, Yukie Kawano, Yuta Anchi, Tatsuhiro Shibata, Atsushi Suzuki, Mitsunori Nishikawa, Hiroto Ito, Masashi Kato, Tsuyoshi Shiga, Yoshihiro Fukumoto, Chisato Izumi, Satoshi Yasuda, Hisao Ogawa, Yasuo Sugano, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 84, 4, 584, 591, 25 Mar. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: Palliative care is highly relevant for patients with heart failure (HF), and there is a need for quantitative information on quality of care. Accordingly, this study aimed to develop a set of quality indicators (QIs) for palliative care of HF patients, and to conduct a practical pilot measurement of the proposed QIs in clinical practice.Methods and Results:We used a modified Delphi technique, a consensus method that involves a comprehensive literature review, face-to-face multidisciplinary panel meeting, and anonymous rating in 2 rounds. A 15-member multidisciplinary expert panel individually rated each potential indicator on a scale of 1 (lowest) to 9 (highest) for appropriateness. All indicators receiving a median score ≥7 without significant disagreement were included in the final set of QIs. Through the consensus-building process, 35 QIs were proposed for palliative care in HF patients. Practical measurement in HF patients (n=131) from 3 teaching hospitals revealed that all of the proposed QIs could be obtained retrospectively from medical records, and the following QIs had low performance (<10%): "Intervention by multidisciplinary team", "Opioid therapy for patients with refractory dyspnea", and "Screening for psychological symptoms". CONCLUSIONS: The first set of QIs for palliative care of HF patients was developed and could clarify quantitative information and might improve the quality of care.

Measurements of liver stiffness in patients with left ventricular assist device support.
Kazunori Omote, Takuma Sato, Toshiyuki Nagai, Toshihisa Anzai
Heart and vessels, 35, 3, 442, 442, Mar. 2020, [Peer-reviewed], [Domestic magazines]
English

Prognostic Value of Serum Uric Acid in Hospitalized Heart Failure Patients With Preserved Ejection Fraction (from the Japanese Nationwide Multicenter Registry).
Yuta Kobayashi, Kazunori Omote, Toshiyuki Nagai, Kiwamu Kamiya, Takao Konishi, Takuma Sato, Yoshiya Kato, Hirokazu Komoriyama, Shingo Tsujinaga, Hiroyuki Iwano, Kazuhiro Yamamoto, Tsutomu Yoshikawa, Yoshihiko Saito, Toshihisa Anzai
The American journal of cardiology, 125, 5, 772, 776, 01 Mar. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Elevated serum uric acid (UA) is associated with an increased risk of cardiovascular disease and worse clinical outcome in patients with cardiovascular disease. Nevertheless, the prognostic value of serum UA level in hospitalized heart failure patients with preserved ejection fraction (HFpEF) has not been fully elucidated. The aim of this study was to investigate whether serum UA level on admission could be associated with subsequent mortality in hospitalized patients with HFpEF. We examined 516 consecutive hospitalized HFpEF (left ventricular ejection fraction ≥50%) patients with decompensated heart failure from our HFpEF-specific multicenter registry who had serum UA data on admission. The primary outcome of interest was all-cause death. During a median follow-up period of 749 (interquartile range 540 to 831) days, 90 (17%) patients died. Higher serum UA level was significantly related to increased incidence of all-cause death (p = 0.016). In addition, patients with higher serum UA (≥6.6 mg/dl, median) and plasma B-type natriuretic peptide (≥401.2 pg/ml, median) levels had the highest incidence of all-cause death in the groups (p = 0.002). In multivariable Cox regression analysis, serum UA was an independent determinant of mortality (hazards ratio 1.23, 95% confidence interval 1.10 to 1.39) even after adjustment for prespecified confounders, renal function and the use of diuretics before admission. In conclusions, higher admission serum UA was an independent determinant of mortality in hospitalized HFpEF patients. Our findings indicate the importance of assessing admission serum UA level for further risk stratification in hospitalized patients with HFpEF.

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, 25 Feb. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, 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.

Impact of Endovascular Repair on the Outcomes of Octogenarians with Ruptured Abdominal Aortic Aneurysms: A Nationwide Japanese Study.
Tetsuo Yamaguchi, Michikazu Nakai, Yoko Sumita, Kunihiro Nishimura, Toshiyuki Nagai, Toshihisa Anzai, Yasushi Sakata, Hitoshi Ogino
European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery, 59, 2, 219, 225, Feb. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, OBJECTIVE: This study aimed to clarify the impact of endovascular aneurysm repair (EVAR) on clinical outcomes in Japanese patients of advanced age with ruptured abdominal aortic aneurysm (rAAA). METHODS: This was a national registry based retrospective comparative study, using data from the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC), a nationwide claim based database from more than 600 hospitals. Patients admitted with rAAA between April 1, 2012, and March 31, 2015 were included in the study. Patient characteristics, management, and outcomes were compared between the elderly (aged ≥ 80 y) and the less old. The primary endpoint was in hospital mortality; the secondary endpoint was the functional status at discharge. RESULTS: Of 3 969 eligible patients, 49.9% were categorised as elderly. Elderly patients had a higher prevalence of female gender (41.8% vs. 17.0%, p < .001) and disturbance of consciousness on admission (28.6% vs. 20.7%, p < .001). They were less likely to undergo open surgical repair (31.6% vs. 56.7%, p < .001), although EVAR was performed similarly in both groups (13.7% vs. 14.8%, p = .33). The unadjusted mortality rate (61.8% vs. 37.6%, p < .001) and mean Barthel index at discharge (73.0 vs. 91.8, p < .001) were statistically significantly worse in the elderly. Multilevel mixed effect logistic regression analyses showed that old age was detected as an independent predictor of in hospital death (odds ratio 2.75; 95% confidence interval, 2.39-3.17; p < .001). However, for patients who received EVAR, old age was not statistically significant (odds ratio 1.13; 95% confidence interval, 0.77-1.66; p = .53). CONCLUSION: Elderly patients with rAAA were less likely to be offered open surgical repair, and the mortality among those who received surgery was high. However, for the small subgroup of elderly patients currently selected for EVAR there was a favourable outcome. The further implementation of EVAR for rAAA in Japan, especially for elderly patients with suitable anatomy, may be justified.

Left ventricular outflow tract velocity time integral in hospitalized heart failure with preserved ejection fraction.
Kazunori Omote, Toshiyuki Nagai, Hiroyuki Iwano, Shingo Tsujinaga, Kiwamu Kamiya, Tadao Aikawa, Takao Konishi, Takuma Sato, Yoshiya Kato, Hirokazu Komoriyama, Yuta Kobayashi, Kazuhiro Yamamoto, Tsutomu Yoshikawa, Yoshihiko Saito, Toshihisa Anzai
ESC heart failure, 7, 1, 167, 175, Feb. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIMS: The prognostic implication of left ventricular outflow tract velocity time integral (LVOT-VTI) on admission in hospitalized heart failure with preserved ejection fraction (HFpEF) patients has not been determined. We sought to investigate whether LVOT-VTI on admission is associated with worse clinical outcomes in hospitalized patients with HFpEF. METHODS AND RESULTS: We studied consecutive 214 hospitalized HFpEF patients who had accessible LVOT-VTI data on admission, from a prospective HFpEF-specific multicentre registry. The primary outcome of interest was the composite of all-cause death and readmission due to heart failure. During a median follow-up period of 688 (interquartile range 162-810) days, the primary outcome occurred in 83 patients (39%). The optimal cut-off value of LVOT-VTI for the primary outcome estimated by receiver operating characteristic analysis was 15.8 cm. Lower LVOT-VTI was significantly associated with the primary outcome compared with higher LVOT-VTI (P = 0.005). Multivariable Cox regression analyses revealed that lower LVOT-VTI was an independent determinant of the primary outcome (hazard ratio 0.94, 95% confidence interval 0.91-0.98). In multivariable linear regression, haemoglobin level was the strongest independent determinant of LVOT-VTI among clinical parameters (β coefficient = -0.61, P = 0.007). Furthermore, patients with lower LVOT-VTI and anaemia had the worst clinical outcomes among the groups (P < 0.001). CONCLUSIONS: Lower admission LVOT-VTI was an independent determinant of worse clinical outcomes in hospitalized HFpEF patients, indicating that LVOT-VTI on admission might be useful for categorizing a low-flow HFpEF phenotype and risk stratification in hospitalized HFpEF patients.

Viability assessment by 18F-FDG PET in a patient with a large left ventricular aneurysm and obstructive coronary artery disease.
Eigo Kurebayashi, Osamu Manabe, Masanao Naya, Shiro Miura, Takehiro Yamashita, Yoshihiro Imai, Akira Ando, Chihoko Miyazaki, Toshihisa Anzai
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 27, 1, 326, 329, Feb. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal

Serum Brain-Derived Neurotrophic Factor Levels Are Associated with Skeletal Muscle Function but Not with Muscle Mass in Patients with Heart Failure.
Ippei Nakano, Shintaro Kinugawa, Hiroaki Hori, Arata Fukushima, Takashi Yokota, Shingo Takada, Naoya Kakutani, Yoshikuni Obata, Katsuma Yamanashi, Toshihisa Anzai
International heart journal, 61, 1, 96, 102, 31 Jan. 2020, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Heart failure (HF) is associated with aberrant skeletal muscle impairments, which are closely linked to the severity of HF. A low level of brain-derived neurotrophic factor (BDNF), a myokine produced in the skeletal muscle, is known to be involved in reduced exercise capacity and poor prognosis in HF. However, little is known about the factors or conditions of skeletal muscle associated with BDNF levels. We investigated the association between serum BDNF levels and the skeletal muscle mass and function in HF patients (n = 60, 63 ± 13 years) and age-matched controls (n = 29, 61 ± 16 years). The serum BDNF level was significantly lower in the HF patients compared to the controls (24.9 ± 0.9 versus 28.6 ± 1.3, P = 0.021). In a univariate analysis, BDNF was significantly correlated with the peak oxygen uptake, estimated glomerular filtration rate, 10-m gait speed, and muscle strength, but not with the body mass index or lean mass in the HF group. A multiple linear regression analysis revealed that BDNF was independently associated with muscle strength (β-coefficient = 2.80, 95%CI: 1.89-11.8, P = 0.008). Serum BDNF levels were associated with exercise capacity and skeletal muscle function, but not with muscle mass. These novel findings may suggest that BDNF production is controlled by muscle function and activity and consequently regulates exercise capacity, highlighting the importance of adequate training regarding skeletal muscle in HF patients.

Improved regional myocardial blood flow and flow reserve after coronary revascularization as assessed by serial 15O-water positron emission tomography/computed tomography.
Tadao Aikawa, Masanao Naya, Kazuhiro Koyanagawa, Osamu Manabe, Masahiko Obara, Keiichi Magota, Noriko Oyama-Manabe, Nagara Tamaki, Toshihisa Anzai
European heart journal cardiovascular Imaging, 21, 1, 36, 46, 01 Jan. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIMS: Myocardial perfusion imaging without and with quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR) plays an important role in the diagnosis and risk stratification of patients with stable coronary artery disease (CAD). We aimed to quantify the effects of coronary revascularization on regional stress MBF and MFR and to determine whether the presence of subendocardial infarction was associated with these changes. METHODS AND RESULTS: Forty-seven patients with stable CAD were prospectively enrolled. They underwent 15O-water positron emission tomography at baseline and 6 months after optimal medical therapy alone (n = 16), percutaneous coronary intervention (PCI) (n = 18), or coronary artery bypass grafting (CABG) (n = 13). Stenosis of ≥50% diameter was detected in 98/141 vessels (70%). The regional MFR was significantly increased from baseline to follow-up [1.84 (interquartile range, IQR 1.28-2.17) vs. 2.12 (IQR 1.69-2.63), P < 0.001] in vessel territories following PCI or CABG due to an increase in the stress MBF [1.33 (IQR 0.97-1.67) mL/g/min vs. 1.64 (IQR 1.38-2.17) mL/g/min, P < 0.001], whereas there was no significant change in the regional stress MBF or MFR in vessel territories without revascularization. A multilevel mixed-effects models adjusted for baseline characteristics, subendocardial infarction assessed by cardiovascular magnetic resonance imaging, and intra-patient correlation showed that the degree of angiographic improvement after coronary revascularization was significantly associated with increased regional stress MBF and MFR (P < 0.05 for all). CONCLUSION: Coronary revascularization improved the regional stress MBF and MFR in patients with stable CAD. The magnitude of these changes was associated with the extent of revascularization independent of subendocardial infarction.

Dual Gate Doppler法による左房収縮時の血流時相解析
岡田 一範, 岡田 由佳, 加賀 早苗, 村山 迪史, 中鉢 雅大, 横山 しのぶ, 西野 久雄, 三神 大世, 更科 美羽, 辻永 真吾, 岩野 弘幸, 安斉 俊久
超音波検査技術抄録集, 45, S110, S110, 一般社団法人 日本超音波検査学会, 2020
Japanese

Diagnosis, prevention, and treatment of cardiovascular diseases in people with type 2 diabetes and prediabetes: a consensus statement jointly from the Japanese Circulation Society and the Japan Diabetes Society
Eiichi Araki, Atsushi Tanaka, Nobuya Inagaki, Hiroshi Ito, Kohjiro Ueki, Toyoaki Murohara, Kenjiro Imai, Masataka Sata, Takehiro Sugiyama, Hideki Ishii, Shunsuke Yamane, Takashi Kadowaki, Issei Komuro, Koichi Node, Tetsuya Amano, Toshihisa Anzai, Tetsuya Babazono, Masanori Emoto, Keiichi Fukuda, Nobuhisa Hagiwara, Ken ichi Hirata, Yuji Ikari, Takanori Ikeda, Chisato Izumi, Masahiro Jinzaki, Hideaki Kaneto, Hideki Katagiri, Takeshi Kimura, Yoshio Kobayashi, Koji Maemura, Satoaki Matoba, Tetsuo Minamino, Yoshihide Mitani, Shin ichiro Miura, Yoshihio Morino, Jiro Nakamura, Yoshihiko Nishio, Wataru Ogawa, Mitsuru Ohishi, Hiroyuki Okura, Minoru Ono, Yasushi Sakata, Asako Sato, Akira Shimada, Wataru Shimizu, Iichiro Shimomura, Ichiro Shiojima, Masayuki Takamura, Yasutomo Takeishi, Kazuo Tanemoto, Yukio Tanizawa, Yasuo Terauchi, Kazuyuki Tobe, Yayoi Tetsuou, Hirotaka Watada, Toshimasa Yamauchi, Masafumi Yano, Narihito Yoshioka
Diabetology International, 2020
Scientific journal

Emery-Dreifuss muscular dystrophy as a possible cause of coronary embolism.
Atsushi Tada, Takao Konishi, Takuma Sato, Tomoya Sato, Takuya Koizumi, Sakae Takenaka, Yoshifumi Mizuguchi, Takahide Kadosaka, Ko Motoi, Yuta Kobayashi, Hirokazu Komoriyama, Yoshiya Kato, Kazunori Omote, Shingo Tsujinaga, Rui Kamada, Kiwamu Kamiya, Hiroyuki Iwano, Toshiyuki Nagai, Nanase Okazaki, Yoshihiro Matsuno, Toshihisa Anzai
Cardiology journal, 27, 4, 443, 444, 2020, [International Magazine]
English, Scientific journal

心エコー法とMRIによる肺動脈弁逆流重症度に乖離を認めた総動脈幹症の術後症例　　　　　　　　　　　　　　　
岩野 弘幸, 村山 迪史, 山澤 弘州, 武田 充人, 真鍋 徳子, 石森 直樹, 千葉 泰之, 石坂 傑, 更科 美羽, 辻永 真吾, 中鉢 雅大, 加賀 早苗, 安斉 俊久
日本成人先天性心疾患学会雑誌, 9, 1, 288, 288, 日本成人先天性心疾患学会, Jan. 2020, [Peer-reviewed]
Japanese

心エコー法とMRIによる肺動脈弁逆流重症度に乖離を認めた総動脈幹症の術後症例　　　　　　　　　　　　　　　
岩野 弘幸, 村山 迪史, 山澤 弘州, 武田 充人, 真鍋 徳子, 石森 直樹, 千葉 泰之, 石坂 傑, 更科 美羽, 辻永 真吾, 中鉢 雅大, 加賀 早苗, 安斉 俊久
日本成人先天性心疾患学会雑誌, 9, 1, 288, 288, 日本成人先天性心疾患学会, Jan. 2020, [Peer-reviewed]
Japanese

Histopathologically confirmed very late stent thrombosis associated with stent fracture after implantation of first-generation drug eluting stent.
Takao Konishi, Naohiro Funayama, Tadashi Yamamoto, Daisuke Hotta, Yuta Kobayashi, Hirokazu Komoriyama, Yoshiya Kato, Kazunori Omote, Takuma Sato, Kiwamu Kamiya, Toshiyuki Nagai, Shinya Tanaka, Toshihisa Anzai
Cardiology journal, 27, 2, 204, 205, 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal

18F-FMISO PET/CT detects hypoxic lesions of cardiac and extra-cardiac involvement in patients with sarcoidosis.
Sho Furuya, Masanao Naya, Osamu Manabe, Kenji Hirata, Hiroshi Ohira, Tadao Aikawa, Kazuhiro Koyanagawa, Keiichi Magota, Ichizo Tsujino, Toshihisa Anzai, Yuji Kuge, Noriko Oyama-Manabe, Kohsuke Kudo, Tohru Shiga, Nagara Tamaki
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 28, 5, 2141, 2148, 09 Dec. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: 18F-fluoromisonidazole (FMISO) is a hypoxia positron emission tomography (PET) tracer. Here, we evaluated cardiac and extra-cardiac sarcoidosis using both FMISO and 18F-fluorodeoxyglucose (FDG) PET/CT in a prospective cohort of patients with sarcoidosis. METHODS: Ten consecutive sarcoidosis patients with suspected cardiac involvement were prospectively enrolled. Each patient fasted overnight (for ≥ 18 hours) preceded by a low-carbohydrate diet before FDG PET/CT but not given special dietary instructions before the FMISO PET/CT scan. We visually and semiquantitatively assessed the uptakes of FMISO and FDG using the maximal standardized uptake value (SUVmax). The metabolic volume (MV) of FDG was calculated as the volume within the boundary determined by the threshold (mean SUV of blood pool × 1.5). RESULTS: Nine patients showed focal FDG uptake in the myocardium and were diagnosed with cardiac sarcoidosis. Among the patients with extra-cardiac lesions, FDG uptake was seen in 8 lymph nodes and 3 lung lesions. FMISO uptake was seen in the 7 cardiac (77.8%) and 6 extra-cardiac (54.5%) lesions. None of the patients showed physiological FMISO uptake in the myocardium. The SUVmax values of the lesions with FMISO uptake were higher than those of the lesions without FMISO uptake in both the cardiac (SUVmax: 9.9, IQR: 8.4-10.0 vs 7.3, IQR: 6.3-8.2) and non-cardiac lesions (SUVmax: 17.6, IQR: 14.5-19.3 vs 6.1, IQR: 5.9-6.2; P = 0.006). The MV values of the lesions with FMISO uptake were significantly higher than those of the lesions without FMISO uptake (111.3, IQR: 78.3-135.7 vs 6.4, IQR: 1.9-23.3; P = 0.0009). CONCLUSIONS: FMISO showed no physiological myocardial uptake and did not require special preparation. FMISO PET has the potential to detect hypoxic lesions in patients with sarcoidosis.

Evidence-Based Utilization of Prognostic Prediction Models in Cardiovascular Medicine.
Naotsugu Iwakami, Toshiyuki Nagai, Toshiaki A Furukawa, Kunihiro Nishimura, Toshihisa Anzai
Circulation reports, 2, 1, 10, 16, 05 Dec. 2019, [Domestic magazines]
English, Scientific journal, Prediction models are combinations of predictors to assess the risks of specific endpoints such as the presence or prognosis of a disease. Many novel predictors have been developed, modelling techniques have been evolving, and prediction models are currently abundant in the medical literature, especially in cardiovascular medicine, but evidence is still lacking regarding how to use them. Recent methodological advances in systematic reviews and meta-analysis have enabled systematic evaluation of prediction model studies and quantitative analysis to identify determinants of model performance. Knowing what is critical to model performance, under what circumstances model performance remains adequate, and when a model might require further adjustment and improvement will facilitate effective utilization of prediction models and will enhance diagnostic and prognostic accuracy in clinical practice. In this review article, we provide a current methodological overview of the attempts to implement evidence-based utilization of prognostic prediction models for all potential model users, including patients and their families, health-care providers, administrators, researchers, guideline developers and policy makers.

Long-term Prognostic Significance of Admission Tricuspid Regurgitation Pressure Gradient in Hospitalized Patients With Heart Failure With Preserved Ejection Fraction: A Report From the Japanese Real-World Multicenter Registry.
Kazunori Omote, Toshiyuki Nagai, Kiwamu Kamiya, Tadao Aikawa, Shingo Tsujinaga, Yoshiya Kato, Hirokazu Komoriyama, Hiroyuki Iwano, Kazuhiro Yamamoto, Tsutomu Yoshikawa, Yoshihiko Saito, Toshihisa Anzai
Journal of cardiac failure, 25, 12, 978, 985, Dec. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Doppler-estimated peak systolic tricuspid regurgitation pressure gradient (TRPG) is a representative noninvasive parameter for evaluating pulmonary artery systolic pressure, which can be a determinant of adverse outcomes in chronic heart failure with preserved ejection fraction (HFpEF). However, the prognostic implications of TRPG at admission for hospitalized patients with HFpEF are undetermined. METHODS AND RESULTS: We examined 469 consecutive hospitalized patients with decompensated HFpEF (left ventricular ejection fraction ≥ 50%) who underwent TRPG measurement at admission in our HFpEF multicenter registry. The primary outcome of interest was all-cause death. Admission TRPG was significantly correlated with estimated pulmonary capillary wedge pressure and left atrial dimension (r = 0.24, P < 0.001 and r = 0.21, P < 0.001, respectively). During a median follow-up period of 748 (IQR 540-820) days, 83 patients died. Higher TRPG was significantly associated with higher mortality compared to lower TRPG (log-rank; P = 0.007). Multivariable analysis revealed that elevated TRPG was an independent determinant of mortality (HR 1.02, 95% CI 1.01-1.04, P = 0.008) after adjustment for prespecified confounders and renal function. CONCLUSIONS: Elevated TRPG at admission was an independent determinant of mortality in hospitalized patients with HFpEF, indicating that TRPG at admission could be a useful marker for risk stratification in these patients.

収縮機能維持の心不全入院患者における入院時の三尖弁逆流圧較差の長期予後的意義 多施設レジストリーからの報告 TRPGとHFpEFにおける長期転帰(Long-term prognostic significance of admission tricuspid regurgitation pressure gradient in hospitalized heart failure patients with preserved ejection fraction: a report from the Japanese real-world multicenter registry: TRPG and long-term outcomes in HFpEF)
Omote Kazunori, Nagai Toshiyuki, Kamiya Kiwamu, Aikawa Tadao, Tsujinaga Shingo, Kato Yoshiya, Komoriyama Hirokazu, Iwano Hiroyuki, Yamamoto Kazuhiro, Yoshikawa Tsutomu, Saito Yoshihiko, Anzai Toshihisa
福田記念医療技術振興財団情報, 32, 41, 54, (公財)福田記念医療技術振興財団, Dec. 2019
English

A mitochondrial delivery system using liposome-based nanocarriers that target myoblast cells.
Takashi Katayama, Shintaro Kinugawa, Shingo Takada, Takaaki Furihata, Arata Fukushima, Takashi Yokota, Toshihisa Anzai, Mitsue Hibino, Hideyoshi Harashima, Yuma Yamada
Mitochondrion, 49, 66, 72, Nov. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Mitochondrial function is reduced in skeletal muscles of many patients with systemic diseases and it is difficult to deliver medicinal substances to mitochondria in such tissue. In this study, we report on attempts to develop liposome-based carriers for mitochondrial delivery using mouse myoblasts (C2C12) by varying the lipid composition of the carriers. We found that a liposome that contains an optimal lipid modified with the KALA peptide (a cellular uptake and mitochondrial targeting device) was the most effective nanocarrier for achieving mitochondrial delivery in C2C12 cells. We also report on successful mitochondrial transgene expression using the carriers encapsulating a mitochondrial DNA vector as we previously reported.

Impact of Left Ventricular Suction During Exercise on Clinical Outcomes in Patients With Heart Failure
Shingo Tsujinaga, Hiroyuki Iwano, Suguru Ishizaka, Yasuyuki Chiba, Miwa Sarashina, Michito Murayama, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Kazunori Okada, Sanae Kaga, Takuma Sato, Toshihisa Anzai
CIRCULATION, 140, Nov. 2019, [Peer-reviewed]
English

JCS 2016 Guideline on Diagnosis and Treatment of Cardiac Sarcoidosis - Digest Version.
Fumio Terasaki, Arata Azuma, Toshihisa Anzai, Nobukazu Ishizaka, Yoshio Ishida, Mitsuaki Isobe, Takayuki Inomata, Hatsue Ishibashi-Ueda, Yoshinobu Eishi, Masafumi Kitakaze, Kengo Kusano, Yasushi Sakata, Noriharu Shijubo, Akihito Tsuchida, Hiroyuki Tsutsui, Takatomo Nakajima, Satoshi Nakatani, Taiko Horii, Yoshikazu Yazaki, Etsuro Yamaguchi, Tetsuo Yamaguchi, Tomomi Ide, Hideo Okamura, Yasuchika Kato, Masahiko Goya, Mamoru Sakakibara, Kyoko Soejima, Toshiyuki Nagai, Hiroshi Nakamura, Takashi Noda, Takuya Hasegawa, Hideaki Morita, Tohru Ohe, Yasuki Kihara, Yoshihiko Saito, Yukihiko Sugiyama, Shin-Ichiro Morimoto, Akira Yamashina
Circulation journal : official journal of the Japanese Circulation Society, 83, 11, 2329, 2388, 25 Oct. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Mitochondrial reactive oxygen species generation in blood cells is associated with disease severity and exercise intolerance in heart failure patients.
Ryosuke Shirakawa, Takashi Yokota, Takayuki Nakajima, Shingo Takada, Miwako Yamane, Takaaki Furihata, Satoshi Maekawa, Hideo Nambu, Takashi Katayama, Arata Fukushima, Akimichi Saito, Naoki Ishimori, Flemming Dela, Shintaro Kinugawa, Toshihisa Anzai
Scientific reports, 9, 1, 14709, 14709, 11 Oct. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Systemic oxidative stress plays a key role in the development of chronic heart failure (CHF). We tested the hypothesis that mitochondrial reactive oxygen species (ROS) generation in circulating peripheral blood mononuclear cells (PBMCs) contributes to CHF progression. A total of 31 patients who had a history of hospital admission due to worsening HF were enrolled and grouped as having either mild CHF defined as New York Heart Association (NYHA) functional class I-II or moderate-to-severe CHF defined as NYHA functional class III. ROS levels in PBMC mitochondria were significantly increased in CHF patients with NYHA functional class III compared to those with NYHA functional class I-II, accompanied by impaired mitochondrial respiratory capacity in PBMCs. ROS generation in PBMC mitochondria was positively correlated with urinary 8-hydroxydeoxyguanosine, a systemic oxidative stress marker, in CHF patients. Importantly, mitochondrial ROS generation in PBMCs was directly correlated with plasma levels of B-type natriuretic peptide, a biomarker for severity of HF, and inversely correlated with peak oxygen uptake, a parameter of exercise capacity, in CHF patients. The study showed that ROS generation in PBMC mitochondria was higher in patients with advanced CHF, and it was associated with disease severity and exercise intolerance in CHF patients.

The rate of myocardial perfusion recovery after steroid therapy and its implication for cardiac events in cardiac sarcoidosis and primarily preserved left ventricular ejection fraction.
Kazuhiro Koyanagawa, Masanao Naya, Tadao Aikawa, Osamu Manabe, Sho Furuya, Masato Kuzume, Noriko Oyama-Manabe, Hiroshi Ohira, Ichizo Tsujino, Toshihisa Anzai
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 28, 4, 1745, 1756, 11 Oct. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Sarcoidosis is a multisystemic disorder of unknown cause characterized by immune granuloma formation in the involved organs. Few studies have reported on the myocardial perfusion changes by immunosuppression therapy in cardiac sarcoidosis (CS). Additionally, the relationship between myocardial perfusion changes and prognosis is unknown. Therefore, this study aimed to clarify myocardial perfusion recovery after steroid therapy and its prognostic value for major adverse cardiac events (MACE) in patients with CS. METHODS AND RESULTS: Thirty-eight consecutive patients with CS {median age, 63 [interquartile range (IQR) 51-68] years; 10 men} underwent both 18F-fluorodeoxyglucose positron emission tomography/computed tomography (CT) and electrocardiography-gated single-photon emission CT (SPECT) pre- and post-steroid therapy. Patients with improved or preserved myocardial perfusion after post-therapy were defined as the recovery group and those with worsened myocardial perfusion as the non-recovery group. Twenty-six patients (68%) were categorized as the recovery group. MACE occurred in eight patients. The Kaplan-Meier curves revealed a significantly higher rate of MACE in the non-recovery group (17.4%/y vs 2.9%/y, P = 0.007). CONCLUSIONS: Myocardial perfusion was recovered by steroid therapy in 61% and preserved in 8% of patients. Myocardial perfusion recovery after steroid therapy was significantly associated with a low incidence of MACE.

Development and validation of support tools for advance care planning in patients with chronic heart failure.
Yasuko Takada, Yasuhiro Hamatani, Yukie Kawano, Yuta Anchi, Michikazu Nakai, Chisato Izumi, Satoshi Yasuda, Hisao Ogawa, Yasuo Sugano, Toshihisa Anzai, Tatsuhiro Shibata, Atsushi Suzuki, Mitsunori Nishikawa, Hiroto Ito, Masashi Kato, Tsuyoshi Shiga, Yoshihiro Fukumoto
International journal of palliative nursing, 25, 10, 494, 502, 02 Oct. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Advance care planning (ACP) is recommended as part of the management of patients with heart failure (HF). AIMS: To develop and validate ACP support tools for patients with HF. METHODS: An ACP support tool was developed based on a systematic literature review. A multi-center, prospective before and after study was conducted to evaluate the usefulness of the support tool. This study included 21 patients with HF, 11 patients formed the control group and 10 patients were part of the intervention group who received ACP from medical staff using the ACP support tools developed for this study. Participants of the study were surveyed about their experience of ACP using a 6-point Likert scale. FINDINGS: All of the healthcare professionals (n=9) involved in the study found the ACP tool useful and about 90% of patients considered the support tool useful. The score for 'the patient did not feel anxious about the future after receiving ACP discussion' was significantly higher (3.5 [3.0, 4.0] vs 2.0 [1.0, 3.0]; P=0.04) in the intervention group that used the ACP tool. CONCLUSION: ACP support tools are useful to manage patients with HF and could enable effective ACP without increasing patient anxiety.

心臓サルコイドーシス診療におけるFDG-PETによる活動性評価をガイドとした免疫抑制療法戦略の限界
永井 利幸, 相川 忠夫, 安斉 俊久
日本サルコイドーシス/肉芽腫性疾患学会雑誌, 39, 1-2, 73, 76, 日本サルコイドーシス, Oct. 2019, [Peer-reviewed]
Japanese

心筋サルコイドーシスにおける心筋血流の改善から予想される心イベントの減少化(Improvement in myocardial perfusion predicts fewer cardiac events in cardiac sarcoidosis)　　　　　　　　　　　　　　　
小梁川 和宏, 納谷 昌直, 相川 忠夫, 真鍋 治, 古家 翔, 葛目 将人, 真鍋 徳子, 大平 洋, 辻野 一三, 安斉 俊久
核医学, 56, Suppl., S137, S137, (一社)日本核医学会, Oct. 2019, [Peer-reviewed]
English

Hyponatremia at discharge is associated with adverse prognosis in acute heart failure syndromes with preserved ejection fraction: a report from the JASPER registry.
Yu Sato, Akiomi Yoshihisa, Masayoshi Oikawa, Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Kazuhiro Yamamoto, Yasuchika Takeishi, Toshihisa Anzai
European heart journal. Acute cardiovascular care, 8, 7, 623, 633, Oct. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, INTRODUCTION: Hyponatremia predicts adverse prognosis in patients with heart failure in particular with reduced ejection fraction. In contrast, it has recently been reported that hyponatremia on admission is not a predictor of post-discharge mortality in patients with heart failure with preserved ejection fraction. We investigated the prognostic impact of hyponatremia at discharge in patients with heart failure with preserved ejection fraction and its clinical characteristics. METHODS AND RESULTS: The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese patients hospitalised with heart failure with preserved ejection fraction and left ventricular ejection fraction of 50% or greater. Five hundred consecutive patients were enrolled in this analysis. We divided the patients into two groups based on their sodium serum levels at discharge: hyponatremia group (sodium <135 mEq/L, n=50, 10.0%) and control group (sodium ⩾135 mEq/L, n=450, 90.0%). This present analysis had two primary endpoints: all-cause death and all-cause death or rehospitalisation for heart failure. At discharge, the hyponatremia group had lower systolic blood pressure (110.0 mmHg vs. 114.5 mmHg, P=0.014) and higher levels of urea nitrogen (31.9 mg/dL vs. 24.2 mg/dL, P=0.032). In the Kaplan-Meier analysis, more patients in the hyponatremia group reached the primary endpoints than those in the control group (log rank <0.01, respectively). In the Cox proportional hazard analysis, hyponatremia at discharge was a predictor of the two endpoints (all-cause death, hazard ratio 2.708, 95% confidence interval 1.557-4.708, P<0.001; all-cause death or rehospitalisation for heart failure, hazard ratio 1.829, 95% confidence interval 1.203-2.780, P=0.005). CONCLUSIONS: Hyponatremia at discharge is associated with adverse prognosis in hospitalised patients with heart failure with preserved ejection fraction.

Simple and noninvasive method to estimate right ventricular operating stiffness based on echocardiographic pulmonary regurgitant velocity and tricuspid annular plane movement measurements during atrial contraction.
Michito Murayama, Kazunori Okada, Sanae Kaga, Hiroyuki Iwano, Shingo Tsujinaga, Miwa Sarashina, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Mutsumi Nishida, Hitoshi Shibuya, Nobuo Masauzi, Toshihisa Anzai, Taisei Mikami
The international journal of cardiovascular imaging, 35, 10, 1871, 1880, Oct. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, It was recently shown that invasively determined right ventricular (RV) stiffness was more closely related to the prognosis of patients with pulmonary hypertension than RV systolic function. So far, a completely noninvasive method to access RV stiffness has not been reported. We aimed to clarify the clinical usefulness of our new echocardiographic index of RV operating stiffness using atrial-systolic descent of the pulmonary artery-RV pressure gradient derived from pulmonary regurgitant velocity (PRPGDAC) and tricuspid annular plane movement during atrial contraction (TAPMAC). We studied 81 consecutive patients with various cardiac diseases who underwent echocardiography and cardiac catheterization. We measured PRPGDAC and TAPMAC using continuous-wave Doppler and M-mode echocardiography, respectively, and calculated PRPGDAC/TAPMAC. RV end-diastolic pressure (RVEDP) and RV pressure increase during atrial contraction (ΔRVPAC) were invasively measured, and RV volume change during atrial contraction (ΔVAC) was calculated from echocardiographic late-diastolic transtricuspid flow time-velocity integral and tricuspid annular area; thus ΔRVPAC/ΔVAC was used as the standard index for RV operating stiffness. PRPGDAC/TAPMAC well correlated with ΔRVPAC/ΔVAC (r = 0.84, p < 0.001) and RVEDP (r = 0.80, p < 0.001), and the area under the receiver operating characteristic curve to discriminate RVEDP > 12 mmHg was 0.94. Multivariate regression analysis revealed that PRPGDAC/TAPMAC was the single independent determinant of ΔRVPAC/ΔVAC (β = 0.86, p < 0.001). PRPGDAC/TAPMAC is useful to estimate RV operating stiffness and a good practical indicator of RVEDP.

Long-Term Tolvaptan Treatment in Refractory Heart Failure.
Teruhiko Imamura, Shintaro Kinugawa, Toshihiro Muramatsu, Tsuyoshi Shiga, Akiyoshi Ogimoto, Toshihisa Anzai, Nobuhisa Hagiwara, Hiroyuki Tsutsui, Issei Komuro, Koichiro Kinugawa
Circulation reports, 1, 10, 431, 437, 26 Sep. 2019, [Domestic magazines]
English, Scientific journal, Background: The vasopressin type-2 receptor antagonist tolvaptan is an essential tool in the management of decompensated heart failure (HF) in the inpatient setting for short-term use with careful monitoring. There is conflicting evidence, however, for its long-term use. Methods and Results: In this prospective, multi-center, open-labeled, randomized control trial, Assessment of QUAlity of life during long-term treatment of ToLVaptan in refractory HF (AQUA-TLV study), patients with congestive HF refractory to furosemide ≥60 mg/day were randomly assigned to a control group or tolvaptan add-on group and followed for 6 months, after confirmation of baseline urine osmolality ≥350 mOsm/L. Twenty-nine patients (median age, 60 years; 22 male) were enrolled and assigned to a control group (n=16) or a tolvaptan group (n=13). Minnesota Living with Heart Failure Questionnaire score improved significantly in the tolvaptan group (from 58 to 10, P=0.030). In the tolvaptan group, diuretics dose reduced (P=0.001), serum creatinine decreased (P=0.040), and hyponatremia tended to improve (P=0.12). The tolvaptan group had a lower HF readmission rate compared with the control group (0.213 vs. 1.242 events/year, P=0.13). Conclusions: Six-month tolvaptan therapy improved quality of life and renal function and reduced HF readmissions, when given to the estimated responders (UMIN Clinical Trial Registry Number: UMIN 000009604).

JCS 2017/JHFS 2017 Guideline on Diagnosis and Treatment of Acute and Chronic Heart Failure - Digest Version.
Hiroyuki Tsutsui, Mitsuaki Isobe, Hiroshi Ito, Hiroshi Ito, Ken Okumura, Minoru Ono, Masafumi Kitakaze, Koichiro Kinugawa, Yasuki Kihara, Yoichi Goto, Issei Komuro, Yoshikatsu Saiki, Yoshihiko Saito, Yasushi Sakata, Naoki Sato, Yoshiki Sawa, Akira Shiose, Wataru Shimizu, Hiroaki Shimokawa, Yoshihiko Seino, Koichi Node, Taiki Higo, Atsushi Hirayama, Miyuki Makaya, Tohru Masuyama, Toyoaki Murohara, Shin-Ichi Momomura, Masafumi Yano, Kenji Yamazaki, Kazuhiro Yamamoto, Tsutomu Yoshikawa, Michihiro Yoshimura, Masatoshi Akiyama, Toshihisa Anzai, Shiro Ishihara, Takayuki Inomata, Teruhiko Imamura, Yu-Ki Iwasaki, Tomohito Ohtani, Katsuya Onishi, Takatoshi Kasai, Mahoto Kato, Makoto Kawai, Yoshiharu Kinugasa, Shintaro Kinugawa, Toru Kuratani, Shigeki Kobayashi, Yasuhiko Sakata, Atsushi Tanaka, Koichi Toda, Takashi Noda, Kotaro Nochioka, Masaru Hatano, Takayuki Hidaka, Takeo Fujino, Shigeru Makita, Osamu Yamaguchi, Uichi Ikeda, Takeshi Kimura, Shun Kohsaka, Masami Kosuge, Masakazu Yamagishi, Akira Yamashina
Circulation journal : official journal of the Japanese Circulation Society, 83, 10, 2084, 2184, 25 Sep. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Change in the NT-proBNP/Mature BNP Molar Ratio Precedes Worsening Renal Function in Patients With Acute Heart Failure: A Novel Predictor Candidate for Cardiorenal Syndrome.
Hiroyuki Takahama, Toshio Nishikimi, Seiji Takashio, Tomohiro Hayashi, Chiaki Nagai-Okatani, Takashi Asada, Akihiro Fujiwara, Yasuaki Nakagawa, Masashi Amano, Yasuhiro Hamatani, Atsushi Okada, Makoto Amaki, Takuya Hasegawa, Hideaki Kanzaki, Kunihiro Nishimura, Satoshi Yasuda, Kenji Kangawa, Toshihisa Anzai, Naoto Minamino, Chisato Izumi
Journal of the American Heart Association, 8, 17, e011468, 03 Sep. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Background Early detection for worsening renal function (WRF) is indispensable in patients with acute decompensated heart failure (HF). We tested the hypothesis that the difference in the circulating levels of each B-type or brain natriuretic peptide (BNP) molecular form is associated with the occurrence of WRF. Methods and Results Circulating levels of proBNP, the NT-proBNP (N-terminal proBNP), and total BNP (proBNP+mature BNP) were prospectively measured in patients with acute decompensated HF using specific and sensitive enzyme immunochemiluminescent assays. An estimated mature BNP (emBNP) concentration was calculated by subtracting proBNP levels from total BNP levels. WRF was defined as a >20% decrease in the estimated glomerular filtration rate during the hospitalization. One-way repeated-measures ANOVA was used to compare the changes of variables between the patients with and without WRF. In patients with acute decompensated HF (New York Heart Association class III-IV; 96%) hospitalized for HF, NT-proBNP levels did not differ during the hospitalization between patients with and without WRF (n=42 and 140, respectively). By contrast, emBNP levels were lower in patients with WRF than in those without WRF on day 3 after admission. NT-proBNP/emBNP molar ratios were elevated on day 3 after admission in the patients with WRF, before estimated glomerular filtration rate declined, but were unchanged in patients without WRF. On day 3 after hospital admission, NT-proBNP/emBNP ratios were strongly associated with percentage decreases in estimated glomerular filtration rate. Conclusions These findings suggest that elevation of NT-proBNP/emBNP ratio precedes WRF in patients with acute HF and can be a potentially useful biomarker for risk stratification of cardiorenal syndrome.

Combined heart and kidney transplantation-Is there a protective effect against cardiac allograft vasculopathy using intravascular ultrasound?
Takuma Sato, Richard Cheng, Babak Azarbal, Michelle Kittleson, Jignesh Patel, Lawrence Czer, Ryan Levine, Sadia Dimbil, Michael Olymbios, Toshihisa Anzai, Evan Kransdorf, David H Chang, Michele A Hamilton, Fardad Esmailian, Jon Kobashigawa
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 38, 9, 956, 962, Sep. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Because cardiac and renal disease are physiologically related and often coexist, the prevalence of combined heart and kidney transplantation (HKTx) has significantly increased over the last few years. It has been suggested that combined organ allografts modulate the immune system favorably for one or both allografts resulting in successful clinical outcomes. However, whether the addition of kidney transplantation has a protective immune effect against developing cardiac allograft vasculopathy (CAV) has not been fully investigated. METHODS: From March 2010 to September 2018, 30 HKTx recipients who had baseline (4-6 weeks) and 1-year intravascular ultrasound (IVUS) were matched with 60 isolated heart transplant (HTx-alone) recipients using propensity scores. First-year changes in maximal intimal thickness (MIT), maximal intimal area (MIA), maximal percent stenosis (MPS), percent atheroma volume (PAV), and incidence of rapid plaque progression were compared between the groups. RESULTS: First-year coronary plaque progression was significantly decreased in HKTx recipients compared with HTx-alone recipients by change in the MIT (0.11 ± 0.14 mm vs 0.40 ± 0.32 mm, p < 0.001), MIA (0.52 ± 1.52 mm2 vs 1.86 ± 2.68 mm2, p = 0.002), MPS (2.10% ± 5.64 percentage points vs 7.22% ± 8.59 percentage points, p = 0.001), and PAV (1.62% ± 3.07 percentage points vs 5.90% ± 5.92 percentage points, p < 0.001). Rapid plaque progression occurred in 2 of 30 in HKTx (6.7%) and in 22 of 60 HTx alone (36.7%), p = 0.002. CONCLUSIONS: Combined heart and kidney transplantation is associated with a decrease in CAV by coronary plaque progression on IVUS. These results suggest that HKTx may have an immune modulating benefit over HTx alone.

Tricuspid regurgitation occurring in the early-diastolic phase in a case of heart failure: Insights from echocardiographic and invasive hemodynamic findings.
Michito Murayama, Hiroyuki Iwano, Shingo Tsujinaga, Miwa Sarashina, Suguru Ishizaka, Yasuyuki Chiba, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Kazunori Okada, Sanae Kaga, Hitoshi Shibuya, Mutsumi Nishida, Toshihisa Anzai
Echocardiography (Mount Kisco, N.Y.), 36, 9, 1771, 1775, Sep. 2019, [Peer-reviewed], [International Magazine]
English, Although the presence and physiological significance of late-diastolic tricuspid regurgitation (TR) have been reported, those in TR occurring in early diastole have not been well known. We herein first presented a case of heart failure due to dilated cardiomyopathy showing functional TR occurring in the early-diastolic phase in whom the mechanism for its genesis could be precisely assessed from echocardiographic findings and intra-cardiac pressure recordings.

Rapidly Progressive Heart Failure in a Female Carrier of Becker Muscular Dystrophy with No Skeletal Muscle Symptoms.
Hirokazu Komoriyama, Arata Fukushima, Yumi Takahashi, Shintaro Kinugawa, Fusako Sera, Tomohito Ohtani, Akinori Nakamura, Yasushi Sakata, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 58, 17, 2545, 2549, 01 Sep. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Becker muscular dystrophy (BMD) carriers are at risk to developing cardiac dysfunction. The prevalence of female BMD carriers remains underestimated, and the disease progression varies. We herein report the case of a young female BMD carrier who developed dilated cardiomyopathy (DCM) and heart failure without any skeletal muscle signs. Her cardiac dysfunction progressed over a mere two months, resulting in the need for left ventricular assist device implantation. Her case demonstrates that progressive cardiomyopathy can be the only clinical manifestation in some BMD carriers, suggesting the need for a more aggressive implementation of genetic testing in female DCM patients.

POEMS Syndrome Showing Left Ventricular Dysfunction and Extracellular Edema Assessed by Cardiac Magnetic Resonance Imaging.
Yumi Takahashi, Hiroyuki Iwano, Ippei Nakano, Arata Fukushima, Masanao Naya, Ai Shimizu, Yoshihiro Matsuno, Noriko Oyama-Manabe, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 58, 17, 2539, 2543, 01 Sep. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Although cardiac involvement is rare in polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, the clinical course becomes considerably worse on complication with cardiac lesions. The increased release of various cytokines has been observed in the pathogenesis of POEMS syndrome, and serum vascular endothelial growth factor (VEGF) levels are known to be associated with the disease activity. We herein report a patient with POEMS syndrome who showed left ventricular systolic dysfunction and was treated with lenalidmide therapy. Of note, the reduction in extracellular edema in the left ventricular wall was clearly visualized by changes in the native T1 values and extracellular volumes on cardiac magnetic resonance imaging.

Clinical significance of end-diastolic opening of pulmonary valve in a case complicating left ventricular systolic dysfunction.
Hisao Nishino, Hiroyuki Iwano, Sanae Kaga, Mutsumi Nishida, Koji Akizawa, Takanori Teshima, Toshihisa Anzai
Journal of echocardiography, 19, 1, 53, 55, 03 Aug. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Rationale and Design of the CANONICAL Study - Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Canagliflozin for Heart Failure With Preserved Ejection Fraction With Type 2 Diabetes Mellitus.
Shu Kasama, Tohru Masuyama, Shiro Uemura, Yukihito Sato, Shinya Hiramitsu, Izuru Masuda, Kazuhiro Yamamoto, Sei Komatsu, Toshihisa Anzai, Kunihiro Nishimura, Tomoya Ueda, Masato Kasahara, Hiroyuki Tanaka, Yutaka Susuta, Yoshihiko Saito
Circulation reports, 1, 8, 347, 351, 03 Aug. 2019, [Domestic magazines]
English, Scientific journal, Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2-I) have beneficial cardiovascular effects, including reduction in hospitalization for heart failure (HF). The aim of this study is to explore the efficacy and safety of canagliflozin compared with standard diabetes treatment in elderly patients with type 2 diabetes (T2DM) and HF with preserved ejection fraction (HFpEF). Methods and Results: This is a multicenter, randomized, open-label, parallel-group comparison study designed to evaluate the effects of canagliflozin on fluid retention and cardiac function in T2DM patients with HFpEF. Eligible participants are patients aged ≥65 years with insufficient glycemic control. Qualified patients will be randomly assigned to treatment with 100 mg of canagliflozin or standard diabetic treatment other than SGLT2-I; both groups will be treated for 24 weeks. The primary endpoints are changes in body weight as an indicator of fluid retention and plasma brain natriuretic peptide as an indicator of cardiac function. The secondary endpoints include cardiovascular event rates, changes in the dose of loop diuretics, echocardiographic left ventricular function, and nutritional status. Conclusions: This study is expected to provide valuable findings regarding the mechanisms of canagliflozin on cardiac function and a potential new therapeutic approach for HFpEF. (UMIN000028668 and jRCTs051180030).

Does ex vivo perfusion lead to more or less intimal thickening in the first-year post-heart transplantation?
Takuma Sato, Babak Azarbal, Richard Cheng, Fardad Esmailian, Jignesh Patel, Michelle Kittleson, Lawrence Czer, Maria Thottam, Ryan Levine, Sadia Dimbil, Michael Olymbios, Toshihisa Anzai, Michele A Hamilton, Tamer Khayal, Jon A Kobashigawa
Clinical transplantation, 33, 8, e13648, Aug. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: The Organ Care System (OCS), an ex vivo heart perfusion platform, represents an alternative to the current standard of cold organ storage that sustains the donor heart in a near-physiologic state. Previous reports showed that this system had significantly shortened the cold ischemic time from standard cold storage (CS). However, the effect of reduced ischemic injury against the coronary vascular bed has not been examined by intravascular ultrasound (IVUS). METHODS: Between August 2011 and February 2013, heart transplant (HTx) candidates enrolled in the PROCEED 2 trial were randomized to either CS or OCS. IVUS was performed at 4-6 weeks (baseline) and repeated 1 year after transplantation. The change in maximal intimal thickness (MIT) and other clinical outcomes were examined. RESULTS: Thirty-nine patients were randomized and underwent HTx by OCS (n=16) or CS (n=18). Of these, 18 patients (OCS: n=5, CS: n=13) with paired IVUS were examined. There were no significant differences in the change of MIT and other clinical outcomes between the groups. CONCLUSION: The incidence of cardiac allograft vasculopathy in donor hearts preserved with the OCS versus CS was similar. These results suggest that this ex vivo allograft perfusion system is a promising and valid platform for donor heart transportation.

Relation of Systolic Blood Pressure on the Following Day with Post-Discharge Mortality in Hospitalized Heart Failure Patients with Preserved Ejection Fraction.
Yu Sato, Akiomi Yoshihisa, Masayoshi Oikawa, Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Kazuhiro Yamamoto, Yasuchika Takeishi, Toshihisa Anzai
International heart journal, 60, 4, 876, 885, 27 Jul. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, The clinical scenario, which is based on systolic blood pressure (SBP) upon admission, is useful for classifying and determining initial treatment for acute heart failure (HF). However, the prognostic significance of SBP following the initial treatment is unclear.The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, and prospective registration of consecutive Japanese patients hospitalized with HF with preserved ejection fraction (HFpEF) and left ventricular ejection fraction ≥ 50%. We divided 525 patients into three groups based on their SBP on the day following hospitalization: high (SBP > 140 mmHg, n = 72, 13.7%); normal (100 ≤ SBP ≤ 140 mmHg, n = 379, 72.2%); and low (SBP < 100 mmHg, n = 74, 14.1%) groups. This analysis had two primary endpoints: (1) all-cause death and (2) all-cause death or rehospitalization for HF. In the Kaplan-Meier analysis, both of the endpoints were the highest in the low group (Log-Rank < 0.05, respectively). Compared to the normal and high groups, the low group demonstrated a higher prevalence of atrial fibrillation (67.1%, 63.9%, and 47.8%, P = 0.026) and the lowest left ventricular outflow tract velocity time integral determined by echocardiography (16.4 cm, 19.4 cm, and 23.3 cm, P = 0.001). In the multivariable Cox proportional hazard analysis, low SBP on the day following hospitalization was an independent predictor of all-cause death (hazard ratio 1.868, 95% confidence interval 1.024-3.407, P = 0.042) and the composite endpoint (hazard ratio 1.660, 95% confidence interval 1.103-2.500, P = 0.015).Classification based on SBP on the day following initial treatment predicts post-discharge prognosis in hospitalized patients with HFpEF.

Serum potassium and glucose levels, and mortality in acute myocardial infarction; fact or myth?
Tadao Aikawa, Toshiyuki Nagai, Toshihisa Anzai
International journal of cardiology, 287, 50, 52, 15 Jul. 2019, [Peer-reviewed], [International Magazine]
English

Validation and Recalibration of Seattle Heart Failure Model in Japanese Acute Heart Failure Patients.
Yasuyuki Shiraishi, Shun Kohsaka, Toshiyuki Nagai, Ayumi Goda, Atsushi Mizuno, Yuji Nagatomo, Yasumori Sujino, Ryoma Fukuoka, Mitsuaki Sawano, Takashi Kohno, Keiichi Fukuda, Toshihisa Anzai, Ramin Shadman, Todd Dardas, Wayne C Levy, Tsutomu Yoshikawa
Journal of cardiac failure, 25, 7, 561, 567, Jul. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Precise risk stratification in heart failure (HF) patients enables clinicians to tailor the intensity of their management. The Seattle Heart Failure Model (SHFM), which uses conventional clinical variables for its prediction, is widely used. We aimed to externally validate SHFM in Japanese HF patients with a recent episode of acute decompensation requiring hospital admission. METHODS AND RESULTS: SHFM was applied to 2470 HF patients registered in the West Tokyo Heart Failure and National Cerebral And Cardiovascular Center Acute Decompensated Heart Failure databases from 2006 to 2016. Discrimination and calibration were assessed with the use of the c-statistic and calibration plots, respectively, in HF patients with reduced ejection fraction (HFrEF; <40%) and preserved ejection fraction (HFpEF; ≥40%). In a perfectly calibrated model, the slope and intercept would be 1.0 and 0.0, respectively. The method of intercept recalibration was used to update the model. The registered patients (mean age 74 ± 13 y) were predominantly men (62%). Overall, 572 patients (23.2%) died during a mean follow-up of 2.1 years. Among HFrEF patients, SHFM showed good discrimination (c-statistic = 0.75) but miscalibration, tending to overestimate 1-year survival (slope = 0.78; intercept = -0.22). Among HFpEF patients, SHFM showed modest discrimination (c-statistic = 0.69) and calibration, tending to underestimate 1-year survival (slope = 1.18; intercept = 0.16). Intercept recalibration (replacing the baseline survival function) successfully updated the model for HFrEF (slope = 1.03; intercept = -0.04) but not for HFpEF patients. CONCLUSIONS: In Japanese acute HF patients, SHFM showed adequate performance after recalibration among HFrEF patients. Using prediction models to tailor the care for HF patients may improve the allocation of medical resources.

Effective blood hemoglobin level to predict prognosis in heart failure with preserved left ventricular ejection fraction: results of the Japanese heart failure syndrome with preserved ejection fraction registry.
Keisuke Okuno, Yoshiro Naito, Masanori Asakura, Masataka Sugahara, Tomotaka Ando, Seiki Yasumura, Toshiyuki Nagai, Yoshihiko Saito, Tsutomu Yoshikawa, Tohru Masuyama, Toshihisa Anzai
Heart and vessels, 34, 7, 1168, 1177, Jul. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, High prevalence of anemia in heart failure with preserved left ventricular ejection fraction (HFpEF) has been reported. However, little is known about the association of anemia and gender with prognosis in HFpEF patients. In addition, effective blood hemoglobin (Hb) level for prognosis in HFpEF patients remains largely unknown. In this study, we investigated the association between anemia, gender, and prognosis in 535 HFpEF patients enrolled in Japanese heart failure syndrome with preserved ejection fraction registry. Furthermore, we assessed effective blood Hb level to predict prognosis in HFpEF patients. According to the World Health Organization criteria, the prevalence rate of anemia on admission was about 70% in both male and female HFpEF patients. Kaplan-Meier analysis for all-cause mortality demonstrated that anemic patients had poor prognosis compared with non-anemic patients in both male and female HFpEF patients. Interestingly, multivariate analysis revealed that blood Hb level at discharge was an independent predictor of all-cause mortality in both male and female HFpEF patients. According to survival classification and regression tree analysis, blood Hb level at discharge of 9.4 g/dL for male and 12.3 g/dL for female was more accurate cutoff value to predict all-cause mortality in HFpEF patients. Anemia was implicated in poor prognosis in both male and female HFpEF patients. In particular, blood Hb level at discharge was an independent predictor of all-cause mortality in both male and female HFpEF patients. Effective cutoff value of blood Hb level at discharge to predict all-cause mortality was lower in male than in female HFpEF patients.

Long-Term Results of Intracardiac Mesenchymal Stem Cell Transplantation in Patients With Cardiomyopathy.
Takeshi Yagyu, Satoshi Yasuda, Noritoshi Nagaya, Kaori Doi, Takeshi Nakatani, Kazuhiro Satomi, Wataru Shimizu, Kengo Kusano, Toshihisa Anzai, Teruo Noguchi, Hajime Ohgushi, Soichiro Kitamura, Kenji Kangawa, Hisao Ogawa
Circulation journal : official journal of the Japanese Circulation Society, 83, 7, 1590, 1599, 25 Jun. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: Mesenchymal stem cells (MSCs), which have the potential to differentiate into cardiomyocytes or vascular endothelial cells, have been used clinically as therapy for cardiomyopathy. In this study, we aimed to evaluate the long-term follow-up results.Methods and Results:We studied 8 patients with symptomatic heart failure (HF) on guideline-directed therapy (ischemic cardiomyopathy, n=3; nonischemic cardiomyopathy, n=5) who underwent intracardiac MSC transplantation using a catheter-based injection method between May 2004 and April 2006. Major adverse events and hospitalizations were investigated up to 10 years afterward. Compared with baseline, there were no significant differences in B-type natriuretic peptide (BNP) (from 211 to 173 pg/mL), left ventricular ejection fraction (LVEF) (from 24% to 26%), and peak oxygen uptake (from 16.5 to 19.2 mL/min/kg) at 2 months. During the follow-up period, no patients experienced serious adverse events such as arrhythmias. Three patients died of pneumonia in the 1st year, liver cancer in the 6th year, and HF in the 7th year. Of the remaining 5 patients, 3 patients were hospitalized for exacerbated HF, 1 of whom required heart transplantation in the 2nd year; 2 patients survived for 10 years without worsening HF. CONCLUSIONS: The results of this exploratory study of intracardiac MSCs administration suggest further research regarding the feasibility and efficacy is warranted.

Survey of Palliative Sedation at End of Life in Terminally Ill Heart Failure Patients - A Single-Center Experience of 5-Year Follow-up.
Yasuhiro Hamatani, Eri Nakai, Emi Nakamura, Michi Miyata, Yukie Kawano, Yasuko Takada, Yuta Anchi, Sayaka Funabashi, Atsushi Hirayama, Kensuke Kuroda, Masashi Amano, Yasuo Sugano, Toshihisa Anzai, Chisato Izumi
Circulation journal : official journal of the Japanese Circulation Society, 83, 7, 1607, 1611, 25 Jun. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: Little is known about palliative sedation in terminally ill heart failure (HF) patients.Methods and Results:We retrospectively reviewed terminally ill HF patients who received palliative sedation from September 2013 to August 2018. Among 95 terminally ill HF patients, 25 were prescribed dexmedetomidine and 12 were prescribed midazolam at the end of life. Richmond Agitation-Sedation Scale was significantly reduced (P<0.01), but blood pressure and heart rate were unaltered after treatment in both the dexmedetomidine and midazolam groups. CONCLUSIONS: Prescription of dexmedetomidine and/or midazolam might be feasible in selected terminally ill HF patients.

冠血行再建治療後の局所心筋血流量と心筋血流予備能の改善メカニズム 15O標識水PETと心臓MRIを用いた検討　　　　　　　　　　　　　　　
相川 忠夫, 納谷 昌直, 小梁川 和宏, 真鍋 治, 真鍋 徳子, 玉木 長良, 安斉 俊久
日本心臓核医学会ニュースレター, 21, 2, 96, 96, 日本心臓核医学会, Jun. 2019, [Peer-reviewed]
Japanese

Impact of admission liver stiffness on long-term clinical outcomes in patients with acute decompensated heart failure.
Kazunori Omote, Toshiyuki Nagai, Naoya Asakawa, Kiwamu Kamiya, Yusuke Tokuda, Tadao Aikawa, Arata Fukushima, Keiji Noguchi, Yoshiya Kato, Hirokazu Komoriyama, Mutsumi Nishida, Yusuke Kudo, Hiroyuki Iwano, Takashi Yokota, Toshihisa Anzai
Heart and vessels, 34, 6, 984, 991, Jun. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Liver stiffness (LS) has been reported to be a marker of liver congestion caused by elevated central venous pressure in heart failure (HF) patients. Recent studies demonstrated that LS could be non-invasively measured by virtual touch quantification (VTQ). However, its prognostic implication in patients with acute decompensated heart failure (ADHF) is unclear. This study sought to determine whether LS measured by VTQ could be a determinant of subsequent adverse events in ADHF patients. We prospectively recruited 70 ADHF patients who underwent LS measurement by VTQ on admission in our university hospital between June 2016 and April 2018. The primary outcome of interest was the composite of all-cause mortality and worsening HF. During a median follow-up period of 272 (interquartile range 122-578) days, there were 26 (37%) events, including 5 (7%) deaths and 21 (30%) cases of worsening HF. The c-index of LS for predicting the composite of adverse events was 0.77 (95% CI 0.66-0.88), and the optimal cut-off value of LS was 1.50 m/s. Adverse events were more frequently observed in patients with high LS (≥ 1.50 m/s) compared to those with low LS (< 1.50 m/s). Multivariable Cox regression analyzes revealed that higher LS was independently associated with increased subsequent risk of adverse events after adjustment for confounders. In conclusion, high admission LS was an independent determinant of worse clinical outcomes in patients with ADHF. This finding suggests that LS on admission is useful for risk stratification of patients with ADHF.

Prognostic impact of chronic obstructive pulmonary disease on adverse prognosis in hospitalized heart failure patients with preserved ejection fraction - A report from the JASPER registry.
Yu Sato, Akiomi Yoshihisa, Masayoshi Oikawa, Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Kazuhiro Yamamoto, Yasuchika Takeishi, Toshihisa Anzai
Journal of cardiology, 73, 6, 459, 465, Jun. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: The prognostic impact of chronic obstructive pulmonary disease (COPD) on heart failure (HF) with preserved ejection fraction (HFpEF) patients and its clinical characteristics have not yet been fully examined. METHODS: The Japanese Heart Failure Syndrome with Preserved Ejection Fraction (JASPER) registry is a nationwide, observational, prospective registration of consecutive Japanese hospitalized HFpEF patients with left ventricular ejection fraction (LVEF) of ≥50%. Among 535 patients enrolled in the registry, 10 lacking COPD data, and seven who died during the first hospitalization, were excluded. Finally, 518 patients were enrolled in this analysis. We divided these patients into two groups: the COPD group (n=40, 7.7%) and the non-COPD group (n=478, 92.3%). This analysis had two primary endpoints: (1) all-cause death and (2) all-cause death or rehospitalization for HF. RESULTS: The COPD group showed a higher prevalence of male sex (70.0% vs. 48.1%, p=0.008), history of prior hospitalization for HF (63.2% vs. 35.1%, p=0.001), smoking history (71.8% vs. 43.3%, p=0.001), and a higher usage of loop diuretics (70.0% vs. 50.0%, p=0.015). In the follow-up period after discharge (median 733 days), there were 82 all-cause deaths and 127 rehospitalizations for HF. In the Kaplan-Meier analysis, the COPD group showed higher all-cause death and reached the composite endpoint more often than in the non-COPD group (all-cause death, log-rank 0.035; all-cause death or rehospitalization for HF, log-rank 0.025). In the Cox proportional hazard analysis, COPD was a predictor of all-cause death (hazard ratio 1.957, 95% confidence interval 1.037-3.694, p=0.038) and the composite endpoint (hazard ratio 1.694, 95% confidence interval 1.064-2.697, p=0.026). CONCLUSIONS: COPD is associated with adverse prognosis in hospitalized patients with HFpEF.

Atrial Fibrillation Does Not Matter in Japanese Ventricular Assist Device Patients? - Half-Way Up the Hill.
Toshiyuki Nagai, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 83, 6, 1202, 1203, 24 May 2019, [Peer-reviewed], [Domestic magazines]
English

Clinical Usefulness of an Echo-Doppler Model in Predicting Elevated Pulmonary Capillary Wedge Pressure in Patients With Heart Failure.
Daigo Chinen, Toshiyuki Nagai, Kazunori Uemura, Yukio Aikawa, Tetsufumi Motokawa, Yasuhide Asaumi, Takeshi Ogo, Hideaki Kanzaki, Teruo Noguchi, Toshihisa Anzai, Wataru Shimizu, Hisao Ogawa, Masaru Sugimachi, Satoshi Yasuda
The American journal of cardiology, 123, 9, 1464, 1469, 01 May 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Although several tissue-Doppler imaging (TDI) models for pulmonary capillary wedge pressure (PCWP) estimation have been reported, their reliability remains uncertain. Our previous theoretical and experimental analyses suggest that right atrial pressure (RAP) corrected by tissue-Doppler imaging tricuspid/mitral annular peak systolic velocities (ST/SM) (RAP × ST/SM) reliably predicts elevated PCWP. We sought to investigate its clinical usefulness for predicting elevated PCWP in heart failure (HF) patients. Ninety-eight patients admitted with HF who underwent right heart catheterization were prospectively studied. RAP and PCWP were measured by right heart catheterization. Simultaneously, ST/SM, early diastolic transmitral flow velocity to mitral annular velocity ratio (E/Ea), and diameter of inferior vena cava at inspiration (IVCDi), a noninvasive surrogate for RAP, were measured by echocardiography. RAP correlated with IVCDi (R2 = 0.57). A significantly stronger correlation was observed between IVCDi corrected by ST/SM (IVCDi × ST/SM) and PCWP than between E/Ea and PCWP (R2 = 0.47 vs 0.18). Receiver-operating characteristic analyses indicated that IVCDi × ST/SM >16 mm predicted PCWP >18 mm Hg with 90% sensitivity and 77% specificity, and the area under the curve was 0.86, which was significantly larger than that of E/Ea (area under the curve=0.72). In conclusions, IVCDi × ST/SM is a new useful noninvasive model to predict elevated PCWP in HF patients.

Prescription Rates of Guideline-Directed Medications Are Associated With In-Hospital Mortality Among Japanese Patients With Acute Myocardial Infarction: A Report From JROAD - DPC Study.
Kazuhiro Nakao, Satoshi Yasuda, Kunihiro Nishimura, Teruo Noguchi, Michikazu Nakai, Yoshihiro Miyamoto, Yoko Sumita, Toshiaki Shishido, Toshihisa Anzai, Hiroshi Ito, Hiroyuki Tsutsui, Yoshihiko Saito, Issei Komuro, Hisao Ogawa
Journal of the American Heart Association, 8, 7, e009692, 02 Apr. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Background The JROAD-DPC (Japanese Registry of All Cardiac and Vascular Diseases Diagnosis Procedure Combination) is a nationwide claims database comprised of the Japanese DPC /Per Diem Payment System. This study aimed to investigate the relationship between prescription rates of guideline-directed medications in each hospital and in-hospital mortality among patients with acute myocardial infarction. Methods and Results A total of 61 838 Japanese patients from 741 hospitals with acute myocardial infarction between 2012 and 2013 were enrolled. The relationship between prescription rates of 4 guideline-directed medications for acute myocardial infarction and in-hospital mortality was analyzed. There were variations in the prescription ratio of β-blockers on admission (median prescription rate 23% [interquartile range 11% to 38%]) and at discharge (51% [36% to 63%]), and of angiotensin converting enzyme/receptor blocker (60% [47% to 70%]). The highest prescription rate quartile of each medication was associated with a significantly lower mortality compared with the lowest prescription rate quartile (aspirin on admission, incidence rate ratio 0.67 [95% CI 0.61-0.74], P<0.001; aspirin at discharge, incidence rate ratio 0.50 [95% CI 0.46-0.55], P<0.001; β-blocker on admission, 0.83 [0.76-0.92], P<0.001; β-blocker at discharge, 0.78 [0.71-0.85], P<0.001; angiotensin converting enzyme/receptor blocker, 0.68 [0.62-0.75], P<0.001; statin, 0.63 [0.57-0.70], P<0.001). The composite prescription score was inversely associated with in-hospital mortality (β coefficient=-0.48, P<0.001) and was closer to the plateau in the high-score range (median mortality for composite prescription scores of 6, 15, and 24 were 10.6%, 6.8%, and 4.6%, respectively). Conclusions The prescription rates of guideline-directed medications for treatment of Japanese acute myocardial infarction patients were inversely associated with in-hospital mortality.

Prolonged QRS duration as a predictor of right ventricular dysfunction after balloon pulmonary angioplasty.
Ryotaro Asano, Takeshi Ogo, Keiko Ohta-Ogo, Shigefumi Fukui, Akihiro Tsuji, Jin Ueda, Nao Konagai, Tetsuya Fukuda, Yoshiaki Morita, Teruo Noguchi, Kengo Kusano, Toshihisa Anzai, Hatsue Ishibashi-Ueda, Satoshi Yasuda
International journal of cardiology, 280, 176, 181, 01 Apr. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Balloon pulmonary angioplasty (BPA) has shown beneficial effects for chronic thromboembolic pulmonary hypertension (CTEPH). However, previous studies have shown less cardiac output improvement and symptoms remaining after BPA, implying poor right ventricular (RV) function recovery. Therefore, we investigated the residual RV dysfunction after BPA to reveal risk factors, clinical effects, and possible underlying histopathological mechanisms. METHODS AND RESULTS: We investigated 61 consecutive CTEPH patients who underwent cardiovascular magnetic resonance before and 3 and 12 months after BPA series. Residual dysfunction (RD) of RV was defined as RV end-diastolic volume index >100 ml/m2 or RV ejection fraction (EF) <45% at 12-month follow-up. Patients were divided into RD (44%) and normalized dysfunction (ND) (56%) groups. Compared with the ND group, the RD group had significantly worse World Health Organization (WHO) functional class at follow-up. No significant hemodynamic differences were observed between the groups. On multivariable logistic regression analysis, male sex (odds ratio [OR] 12.5, p = 0.004) and prolonged QRS duration (OR 1.08, p = 0.029) were independently associated with residual RV dysfunction. Additionally, RV histopathology in 11 CTEPH autopsy cases showed that QRS duration was correlated with RV fibrosis area. CONCLUSIONS: Relatively high percentage (44%) of residual RV dysfunction with worse WHO functional class was observed in CTEPH patients even after BPA. Prolonged QRS duration may predict poor recovery in RV function after BPA.

Effect of intravenous carperitide versus nitrates as first-line vasodilators on in-hospital outcomes in hospitalized patients with acute heart failure: Insight from a nationwide claim-based database.
Toshiyuki Nagai, Naotsugu Iwakami, Michikazu Nakai, Kunihiro Nishimura, Yoko Sumita, Atsushi Mizuno, Hiroyuki Tsutsui, Hisao Ogawa, Toshihisa Anzai
International journal of cardiology, 280, 104, 109, 01 Apr. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUNDS: Carperitide is a recombinantly produced intravenous formulation of human atrial natriuretic peptide. Despite of negative impacts of nesiritide on clinical outcomes for acute heart failure (AHF), carperitide has been used for around a half of Japanese AHF patients as a vasodilator based on limited evidences. We sought to determine the effect of carperitide compared to nitrates in the early care for AHF patients treated with vasodilators. METHODS AND RESULTS: We conducted a cohort study of patients admitted with AHF to 808 hospitals from April 2012 to March 2014. Patients were extracted from 1,422,703 hospitalizations according to ICD-10 heart failure codes. Patients who had sepsis or mechanical supports during hospitalization were excluded. Outcomes were in-hospital death, length of hospitalization and cost of hospitalization. Among 76,924 patients, 45,595 were in patients treated with either carperitide or nitrates during the first 2 days (carperitide; 33,386, nitrates; 12,209). After application of inverse probability of treatment weighting with variables including demographics, comorbidities and treatments, there was perfect balance in both groups. Patients who were treated with carperitide had substantially higher covariate adjusted in-hospital mortality (HR 1.49 95%CI 1.35-1.64), longer length of hospitalization (Coefficients 0.062 95%CI 0.048 to 0.076) and greater cost of hospitalization (Coefficients 0.024 95%CI 0.010 to 0.037) compared to those treated with nitrates. CONCLUSIONS: In Japanese AHF patients during their early inpatient care, carperitide use was significantly associated with worse outcomes when compared to nitrates use, suggesting the routine use of carperitide might not be recommended as a first-line vasodilator for AHF.

Diastolic Intra-Left Ventricular Pressure Difference During Exercise: Strong Determinant and Predictor of Exercise Capacity in Patients With Heart Failure.
Shingo Tsujinaga, Hiroyuki Iwano, Miwa Sarashina, Taichi Hayashi, Michito Murayama, Ayako Ichikawa, Masahiro Nakabachi, Hisao Nishino, Shinobu Yokoyama, Arata Fukushima, Takashi Yokota, Kazunori Okada, Sanae Kaga, Pavlos P Vlachos, Toshihisa Anzai
Journal of cardiac failure, 25, 4, 268, 277, Apr. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Although the enhancement of early-diastolic intra-left ventricular pressure difference (IVPD) during exercise is considered to maintain exercise capacity, little is known about their relationship in heart failure (HF). METHODS AND RESULTS: Cardiopulmonary exercise testing and exercise-stress echocardiography were performed in 50 HF patients (left ventricular [LV] ejection fraction 39 ± 15%). Echocardiographic images were obtained at rest and submaximal and peak exercise. Color M-mode Doppler images of LV inflow were used to determine IVPD. Thirty-five patients had preserved exercise capacity (peak oxygen consumption [VO2] ≥14 mL·kg-1·min-1; group 1) and 15 patients had reduced exercise capacity (group 2). During exercise, IVPD increased only in group 1 (group 1: 1.9 ± 0.9 mm Hg at rest, 4.1 ± 2.0 mm Hg at submaximum, 4.7 ± 2.1 mm Hg at peak; group 2: 1.9 ± 0.8 mm Hg at rest, 2.1 ± 0.9 mm Hg at submaximum, 2.1 ± 0.9 mm Hg at peak). Submaximal IVPD (r = 0.54) and peak IVPD (r = 0.69) were significantly correlated with peak VO2. Peak IVPD determined peak VO2 independently of LV ejection fraction. Moreover, submaximal IVPD could well predict the reduced exercise capacity. CONCLUSION: Early-diastolic IVPD during exercise was closely associated with exercise capacity in HF. In addition, submaximal IVPD could be a useful predictor of exercise capacity without peak exercise in HF patients.

Endomyocardial fibrosis presenting as apical calcification and infective endocarditis.
Tadao Aikawa, Kiwamu Kamiya, Tomoko Mitsuhashi, Toshihisa Anzai
European heart journal, 40, 12, 1016, 1016, 21 Mar. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal

Independent Prognostic Value of Pulmonary Diffusing Capacity in Nonsmoking Patients with Chronic Heart Failure.
Kenji Nakamura, Hideaki Kanzaki, Atsushi Okada, Makoto Amaki, Hiroyuki Takahama, Takuya Hasegawa, Yasuo Sugano, Satoshi Yasuda, Toshihisa Anzai
International heart journal, 60, 2, 366, 373, 20 Mar. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, The diffusing capacity of the lung for carbon monoxide (DLCO) is indicative of the alveolar-capillary membrane function. A reduced DLCO is associated with poor prognosis in chronic heart failure (HF). However, the significance of DLCO as an independent prognostic predictor has not been established. Here, we aimed to determine the prognostic value of DLCO in patients with chronic HF.We enrolled 214 patients (139 females, mean age: 63 ± 16 years, left ventricular ejection fraction [LVEF]: 45 ± 21%) with stable chronic HF who underwent pulmonary function tests. Only never smokers were included in the analysis because smoking can decrease DLCO.During a median follow-up period of 2.1 years, 52 patients (24.3%) experienced cardiac events, including unplanned HF admissions, left ventricular assist device (LVAD) implantations, all-cause deaths, and cardiopulmonary arrests (CPAs). The median percent predicted DLCO (%DLCO) was 87.3%. In a Cox regression analysis, a %DLCO of ≤87.3% was independently associated with the cardiac events, even after adjusting for age, sex, systolic blood pressure (SBP), LVEF, anemia, brain natriuretic peptide, estimated glomerular filtration rate (eGFR), and prior HF admission (hazard ratio [HR]: 1.87, 95% confidence interval: 1.03-3.53, P = 0.030).A reduced DLCO is an independent predictor of poor prognosis in nonsmoking patients with chronic HF.

心血管疾患の非侵襲評価および定量的評価における現在の試み 心血管画像診断のためのハートチームのアプローチ(Our Current Efforts on Noninvasive and Quantitative Assessment of Cardiovascular Disease: A Heart Team Approach for Cardiovascular Imaging)　　　　　　　　　　　　　　　
相川 忠夫, Naya Masanao, Oyama-Manabe Noriko, Koyanagawa Kazuhiro, Manabe Osamu, Anzai Toshihisa
日本循環器学会学術集会抄録集, 83回, RT4, 2, (一社)日本循環器学会, Mar. 2019, [Peer-reviewed]
English

冠血行再建術がPET CTで評価する局所心筋血流予備能に与える影響(The Impact of Coronary Revascularization on Regional Myocardial Flow Reserve Assessed by Positron Emission Tomography)　　　　　　　　　　　　　　　
相川 忠夫, 納谷 昌直, 小梁川 和宏, 真鍋 治, 真鍋 徳子, 安斉 俊久
日本循環器学会学術集会抄録集, 83回, PJ103, 2, (一社)日本循環器学会, Mar. 2019, [Peer-reviewed]
English

心不全患者におけるMRエラストグラフィで評価した肝硬度の増加は右心房圧の上昇を予測する(Increased Liver Stiffness Assessed by Magnetic Resonance Elastography Predicts Elevated Right Atrial Pressure in Patients with Heart Failure)　　　　　　　　　　　　　　　
加藤 喜哉, 永井 利幸, 小森山 弘和, 表 和徳, 相川 忠夫, 神谷 究, 常田 慧徳, 真鍋 徳子[大山], 安斉 俊久
日本循環器学会学術集会抄録集, 83回, PJ096, 6, (一社)日本循環器学会, Mar. 2019, [Peer-reviewed]
English

心筋生検のリンパ管増殖所見は心サルコイドーシスの診断の助けとなる可能性がある(Lymph Vessel Proliferation on Cardiac Biopsy may Help for the Diagnosis of Cardiac Sarcoidosis)
大江 由紀子, 植田 初江, 松山 高明, 永井 利幸, 池田 善彦, 大郷 恵子, 野口 暉夫, 安斉 俊久
日本循環器学会学術集会抄録集, 83回, 2, PJ073, 6, (一社)日本循環器学会, Mar. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal

駆出率が保持されている心不全患者における腎機能悪化の予後的影響 JASPERレジストリからの報告(Prognostic Impact of Worsening Renal Function in Heart Failure Patients with Preserved Ejection Fraction: A Report from the JASPER Registry)
佐藤 悠, 義久 精臣, 及川 雅啓, 永井 利幸, 吉川 勉, 斎藤 能彦, 山本 一博, 竹石 恭知, 安斉 俊久
日本循環器学会学術集会抄録集, 83回, 8, PJ073, 3, (一社)日本循環器学会, Mar. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal

Prognostic value of phase analysis on gated single photon emission computed tomography in patients with cardiac sarcoidosis.
Kazuhiro Koyanagawa, Masanao Naya, Tadao Aikawa, Osamu Manabe, Masato Kuzume, Hiroshi Ohira, Ichizo Tsujino, Nagara Tamaki, Toshihisa Anzai
Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 28, 1, 128, 136, 27 Feb. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: We aimed to determine the correlation between phase analysis, reflecting the heterogeneity of perfusion defects, and the dyssynchrony of the left ventricle wall motion, and adverse cardiac events in cardiac sarcoidosis (CS) patients. METHODS: Fifty-seven consecutive patients with diagnosed CS (64 [IQR 55-71] years old, 14 males), who underwent 18F-FDG PET/CT and ECG-gated SPECT, were studied. FDG PET was analysed to measure cardiac metabolic volume (CMV), and total lesion glycolysis (TLG). The SPECT findings, such as LVEF, Summed Rest Score (SRS), bandwidth (BW) were evaluated. RESULTS: The median of BW was 56° (IQR 40-95). BW showed a strong inverse correlation with LVEF (r = - 0.60, P < 0.0001), and positive correlation with SRS (r = 0.82, P < 0.0001). However, there were no significant correlations between BW and CMV or TLG. The Kaplan-Meier curves revealed a significantly higher rate of MACE in the high BW group (BW > 56°) than the low BW group (BW ≤ 56°) (15.1%/years vs. 4.4%/years, P = 0.025). In multivariable analysis, BW was a significant independent predictor of MACE (P = 0.015). CONCLUSION: Phase analysis on gated SPECT was a significant and independent predictor of MACE in patients with CS.

Comparison of Mortality Prediction Models on Long-Term Mortality in Hospitalized Patients With Acute Heart Failure - The Importance of Accounting for Nutritional Status.
Hiroki Nakano, Kazunori Omote, Toshiyuki Nagai, Michikazu Nakai, Kunihiro Nishimura, Yasuyuki Honda, Satoshi Honda, Naotsugu Iwakami, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Satoshi Yasuda, Hisao Ogawa, Taishiro Chikamori, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 83, 3, 614, 621, 25 Feb. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: The ideal mortality prediction model (MPM) for acute heart failure (AHF) patients would have sufficient and stable predictive ability for long-term as well as short-term mortality. However, published MPMs for AHF predominantly predict short-term mortality up to 90 days, and their prognostic performance for long-term mortality remains unclear. Methods and Results: We analyzed 609 AHF patients in a prospective registry from January 2013 to May 2016. We compared the prognostic performance for long-term mortality among 8 systematically identified MPMs for AHF that predict short-term mortality up to 90 days from admission. The PROTECT 7-day model showed the highest c-index for long-term as well as short-term mortality among the studied MPMs. Sensitivity analyses revealed serum albumin and total cholesterol to be the most important variables, as dropping these variables resulted in a significant decline in c-index, when compared with other variables specific to the PROTECT 7-day model. Furthermore, significant improvements in c-index and net reclassification were observed when serum albumin or serum albumin plus total cholesterol was added to the studied MPMs, other than the PROTECT 7-day model. CONCLUSIONS: The PROTECT 7-day model demonstrated the highest predictive performance for long-term as well as short-term mortality in AHF patients among the published MPMs. Our findings indicate the importance of accounting for nutritional status such as serum albumin and total cholesterol in AHF patients when developing a MPM.

Progressive Mobilization Program for Patients With Acute Heart Failure Reduces Hospital Stay and Improves Clinical Outcome.
Naoya Kakutani, Arata Fukushima, Shintaro Kinugawa, Takashi Yokota, Tatsuya Oikawa, Mikito Nishikawa, Risako Nakamura, Takanori Tsukada, Shigeki Mori, Ichiro Yoshida, Toshihisa Anzai
Circulation reports, 1, 3, 123, 130, 19 Feb. 2019, [Domestic magazines]
English, Scientific journal, Background: Early ambulation has been shown to be associated with shorter hospital stay and better clinical outcomes in patients with acute heart failure (HF). Early mobilization program in combination with structured exercise training is recommended, but has yet to be developed and implemented in HF. Methods and Results: We developed a progressive mobilization program for HF patients that classifies the mobilization process into 7 stages based on disease condition and physical function. We retrospectively analyzed 136 patients with acute HF (80±11 years), who were assigned either to the mobilization program (intervention group, n=75) or to usual care (control group, n=61). The program was safely implemented without any adverse events. Hospital stay was significantly reduced in the intervention group compared with the control group (33±25 vs. 51±36 days, P<0.01). The intervention group had higher activities of daily living (ADL) score at discharge evaluated using the Barthel index (64±38 vs. 49±36, P<0.05). The intervention group also had a higher percentage of discharge to home (71% vs. 52%, P<0.05) and a lower rate of HF-related readmission (16% vs. 36%, P<0.05) compared with the control group. Conclusions: The progressive mobilization program for acute HF was feasible and was associated with better ADL and reduced hospital stay, leading to improvement of clinical outcome.

Arrhythmogenic β-adrenergic signaling in cardiac hypertrophy: The role of small-conductance calcium-activated potassium channels via activation of CaMKII.
Rui Kamada, Hisashi Yokoshiki, Hirofumi Mitsuyama, Masaya Watanabe, Kazuya Mizukami, Taro Tenma, Masayuki Takahashi, Shingo Takada, Toshihisa Anzai
European journal of pharmacology, 844, 110, 117, (一社)日本循環器学会, 05 Feb. 2019, [Peer-reviewed], [International Magazine]
English

Progressive left ventricular dysfunction and myocardial fibrosis in Duchenne and Becker muscular dystrophy: a longitudinal cardiovascular magnetic resonance study.
Tadao Aikawa, Atsuhito Takeda, Noriko Oyama-Manabe, Masanao Naya, Hirokuni Yamazawa, Kazuhiro Koyanagawa, Yoichi M Ito, Toshihisa Anzai
Pediatric cardiology, 40, 2, 384, 392, Feb. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, This study examined the progression of left ventricular dysfunction and myocardial fibrosis in patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) to evaluate the effects of angiotensin-converting enzyme inhibitor (ACEI). Ninety-eight cardiovascular magnetic resonance (CMR) studies in 34 consecutive patients with DMD (n = 21) or BMD (n = 13) were retrospectively reviewed. Left ventricular ejection fraction (LVEF) and the extent of myocardial late gadolinium enhancement (LGE) were semiautomatically quantified. During the study period, five patients had already been treated with ACEI at the first CMR; five were started on ACEI at LVEF ≥ 55% and 10 at LVEF < 55%. All patients had hyperenhanced myocardium on LGE images at the first CMR (median extent, 3.3%; interquartile range 0.1-14.3%). A mixed-effects model for longitudinal data of each patient, adjusted for age, type of muscular dystrophy, steroid use, and ACEI use showed that higher age (β = - 1.1%/year; 95% confidence interval [CI], - 1.8% to - 0.4%; p = 0.005) and no use of ACEI (β = - 3.1%; 95% CI, - 5.4% to - 0.8%; p = 0.009) were significantly associated with a lower LVEF. When ACEI use was stratified by time of initiation (LVEF ≥ 55% vs. < 55%), only ACEI initiation at LVEF < 55% had a beneficial effect on LVEF at each imaging examination (β = 3.7%; 95% CI, 0.9-6.4%; p = 0.010). ACEI use or the time of initiation of ACEI did not significantly affect age-related increase in LGE. ACEI attenuated the age-related decline in LVEF only in patients with DMD or BMD and reduced LVEF, suggesting that further investigation on prophylactic use of cardioprotective therapy in these patients is warranted.

Effect of Statins on Mortality in Heart Failure With Preserved Ejection Fraction Without Coronary Artery Disease - Report From the JASPER Study.
Kyohei Marume, Seiji Takashio, Toshiyuki Nagai, Kenichi Tsujita, Yoshihiko Saito, Tsutomu Yoshikawa, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 83, 2, 357, 367, 25 Jan. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: Statins might be associated with improved survival in patients with heart failure with preserved ejection fraction (HFpEF). The effect of statins in HFpEF without coronary artery disease (CAD), however, remains unclear. Methods and Results: From the JASPER registry, a multicenter, observational, prospective cohort with Japanese patients aged ≥20 years requiring hospitalization with acute HF and LVEF ≥50%, 414 patients without CAD were selected for outcome analysis. Based on prescription of statins at admission, we divided patients into the statin group (n=81) or no statin group (n=333). We followed them for 25 months. The association between statin use and primary (all-cause mortality) and secondary (non-cardiac death, cardiac death, or rehospitalization for HF) endpoints was assessed in the entire cohort and in a propensity score-matched cohort. In the propensity score-matched cohort, 3-year mortality was lower in the statin group (HR, 0.21; 95% CI: 0.06-0.72; P=0.014). The statin group had a significantly lower incidence of non-cardiac death (P=0.028) and rehospitalization for HF (P<0.001), but not cardiac death (P=0.593). The beneficial effect of statins on mortality did not have any significant interaction with cholesterol level or HF severity. CONCLUSIONS: Statin use has a beneficial effect on mortality in HFpEF without CAD. The present findings should be tested in an adequately powered randomized clinical trial.

Superiority of proatrial natriuretic peptide in the prognostic power in patients with acute decompensated heart failure on hospital admission: comparison with B-type natriuretic peptide and other natriuretic peptide forms.
Seiji Takashio, Hiroyuki Takahama, Toshio Nishikimi, Tomohiro Hayashi, Chiaki Nagai-Okatani, Ayaka Matsuo, Yasuaki Nakagawa, Masashi Amano, Yasuhiro Hamatani, Atsushi Okada, Makoto Amaki, Takuya Hasegawa, Hideaki Kanzaki, Satoshi Yasuda, Kenji Kangawa, Toshihisa Anzai, Naoto Minamino, Chisato Izumi
Open heart, 6, 2, e001072, 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Aims: There are significant differences in how atrial (A-type) and B-type natriuretic peptide (ANP and BNP) are secreted and metabolised, but there is little information available about the relative clinical significance of the two peptides. The aim of the present study was to investigate: (1) the association between the circulating level of each ANP molecular form and patient clinical background and (2) their prognostic power for patients with acute decompensated heart failure (ADHF). Methods: We used specific chemiluminescence enzyme immunoassays to prospectively evaluate the levels of six bioactive molecular forms of ANP (pro-ANP, β-ANP and total ANP) and BNP (pro-BNP, N-terminal pro-BNP (NT-pro-BNP) and total BNP) in plasma samples collected from 173 patients with ADHF on their hospital admission. Results: We found that pro-ANP levels were strongly associated with left ventricular (LV) size and ejection fraction (p<0.001), but were not associated with left atrial size. Percent pro-ANP ([pro-ANP/total ANP]x100) was also associated with LV size and function. During the follow-up term (median: 469 days), composite adverse events (all causes of death or rehospitalisation for HF) occurred in 67 patients (38.7 %). Pro-ANP was significantly associated with composite adverse events even after adjusting by estimated glomerular filtration rate (eGFR) (p<0.05). In contrast, NT-pro-BNP was not independent of eGFR in the multivariate analysis. Conclusion: Circulating levels of pro-ANP are strongly associated with LV function and clinical outcomes of patients with ADHF. These findings suggest that during the acute phases of HF, pro-ANP has a prognostic power comparable with NT-pro-BNP independently of renal function.

CORRIGENDUM: Survey of Palliative Sedation at End of Life in Terminally Ill Heart Failure Patients - A Single-Center Experience of 5-Year Follow-up.
Yasuhiro Hamatani, Eri Nakai, Emi Nakamura, Michi Miyata, Yukie Kawano, Yasuko Takada, Yuta Anchi, Sayaka Funabashi, Atsushi Hirayama, Kensuke Kuroda, Masashi Amano, Yasuo Sugano, Toshihisa Anzai, Chisato Izumi
Circulation journal : official journal of the Japanese Circulation Society, 83, 11, 2389, 2389, 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Reduced Myocardial Flow Reserve Is Associated with Subendocardial Infarction and Coronary Stenosis in Patients with Coronary Artery Disease: A Perfusion MRI Study
Osamu Manabe, Noriko Oyama-Manabe, Masanao Naya, Masahiko Obara, Yasuka Kikuchi, Tadao Aikawa, Yuuki Tomiyama, Hiroyuki Sugimori, Chietsugu Katoh, Nagara Tamaki, Toshihisa Anzai
Cardiovascular Imaging Asia, 3, 1, 8, 8, Asian Society of Cardiovascular Imaging, 2019
Scientific journal

Clinical impacts and associated factors of delayed ambulation in patients with acute heart failure
Ishikawa K, Fukushima A, Yokota T, Takada S, Furihata T, Kakutani N, Yamanashi K, Obata Y, Nakano I, Abe T, Kinugawa S, Anzai T
Circ Rep, 1, 4, 179, 186, Japanese Circulation Society, 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Background: In heart failure (HF) management, early ambulation is recommended to prevent physical deconditioning. The effects of delayed ambulation on later clinical outcomes and the factors linked to delayed ambulation in hospitalized HF patients, however, remain unestablished. Methods and Results: We retrospectively investigated 101 patients (mean age, 66±17 years) who were hospitalized for acute decompensated HF. During the mean follow-up of 244±15 days after hospital discharge, 34 patients had cardiovascular events leading to death or unplanned readmission. Patients with cardiovascular events had longer median days to acquire ambulation than those without cardiovascular events (11 days, IQR, 8-20 days vs. 7 days, IQR, 5-15 days, P<0.001). The optimal cut-off period until initiation of ambulation to discriminate cardiovascular events was 8 days, indicating that longer days (≥8 days) to acquire ambulation was associated with higher rates of cardiovascular events, even after adjustment of multiple confounders. On multivariate analysis, age >65 years (odds ratio [OR], 2.49; 95% confidence interval [CI]: 1.04-6.09) and increase in blood urea nitrogen (BUN; OR, 1.04; 95% CI: 1.01-1.08) were independent predictors of delayed ambulation. Conclusions: Delayed ambulation is associated with older age and increased BUN in patients with acute HF. Time to ambulation in the recovery phase of acute HF is important, and delayed ambulation may increase the rate of cardiovascular events after hospital discharge.

Evaluation of the pulmonary artery potential using a 20-polar circumferential catheter and three-dimensional integrated intracardiac echocardiography.
Masayuki Takahashi, Hisashi Yokoshiki, Hirofumi Mitsuyama, Taro Tenma, Masaya Watanabe, Rui Kamada, Ryo Sasaki, Yuki Chiba, Motoki Maeno, Toshihisa Anzai
Heart and vessels, 34, 1, 74, 83, Jan. 2019, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Prolongation of the pulmonary artery potentials (PAPs) in response to short coupling intervals was related to polymorphic QRS configurations during the ventricular tachycardia originating above the pulmonary valve (PA-VT). This prospective study was aimed to investigate the mechanisms of polymorphic changes during the PA-VT. We performed the mapping above the pulmonary valve using a 20-polar circumferential catheter and three-dimensional integrated intracardiac echocardiography in 9 consecutive patients with outflow tract arrhythmias undergoing catheter ablation (UMIN ID: UMIN000021682). The location of successful ablation was right ventricular outflow tract (RVOT) in 6 patients, above the pulmonary valve in 1 patient, left coronary cusp in 1 patient, and unknown in 1 patient. The PAP was detected in six (67%) patients with bipolar voltage of 0.56 ± 0.27 mV. Pacing from bipolar electrodes of the circumferential catheter located above the pulmonary valve captured the PA myocardium only in 1 patient who had the PA-VT (100% in PA-VT vs 0% in non-PA-VT, P = 0.0046), and slight changes of the QRS morphology was observed in accordance with the conduction delay from the stimulus to activation of the RVOT myocardium. The selective PAP capture with conduction delays evoked by bipolar stimulations through a 20-polar circumferential catheter may be a characteristic property of patients with the PA-VT. Conduction delays within the PA and PA-RVOT junction appears to contribute polymorphic QRS changes during the PA-VT.

Effects of coronary revascularization on global coronary flow reserve in stable coronary artery disease.
Tadao Aikawa, Masanao Naya, Masahiko Obara, Osamu Manabe, Keiichi Magota, Kazuhiro Koyanagawa, Naoya Asakawa, Yoichi M Ito, Tohru Shiga, Chietsugu Katoh, Toshihisa Anzai, Hiroyuki Tsutsui, Venkatesh L Murthy, Nagara Tamaki
Cardiovascular research, 115, 1, 119, 129, 01 Jan. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Aims: Coronary flow reserve (CFR) is an integrated measure of the entire coronary vasculature, and is a powerful prognostic marker in coronary artery disease (CAD). The extent to which coronary revascularization can improve CFR is unclear. This study aimed to evaluate the impact of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on CFR in patients with stable CAD. Methods and results: In a prospective, multicentre observational study, CFR was measured by 15O-water positron emission tomography as the ratio of stress to rest myocardial blood flow at baseline and 6 months after optimal medical therapy (OMT) alone, PCI, or CABG. Changes in the SYNTAX and Leaman scores were angiographically evaluated as indicators of completeness of revascularization. Follow-up was completed by 75 (25 OMT alone, 28 PCI, and 22 CABG) out of 82 patients. The median SYNTAX and Leaman scores, and baseline CFR were 14.5 [interquartile range (IQR): 8-24.5], 5.5 (IQR: 2.5-12.5), and 1.94 (IQR: 1.67-2.66), respectively. Baseline CFR was negatively correlated with the SYNTAX (ρ = -0.40, P < 0.001) and Leaman scores (ρ = -0.33, P = 0.004). Overall, only CABG was associated with a significant increase in CFR [1.67 (IQR: 1.14-1.96) vs. 1.98 (IQR: 1.60-2.39), P < 0.001]. Among patients with CFR <2.0 (n = 41), CFR significantly increased in the PCI [1.70 (IQR: 1.42-1.79) vs. 2.21 (IQR: 1.78-2.49), P = 0.002, P < 0.001 for interaction between time and CFR] and CABG groups [1.28 (IQR: 1.13-1.80) vs. 1.86 (IQR: 1.57-2.22), P < 0.001]. The reduction in SYNTAX or Leaman scores after PCI or CABG was independently associated with the percent increase in CFR after adjusting for baseline characteristics (P = 0.012 and P = 0.011, respectively). Conclusion: Coronary revascularization ameliorated reduced CFR in patients with obstructive CAD. The degree of improvement in angiographic CAD burden by revascularization was correlated with magnitude of improvement in CFR.

Severely Impaired Leaflet Mobility of the Tricuspid Valve in an Elderly Woman.
Tatsuro Hitsumoto, Takuya Hasegawa, Yasuhiro Hamatani, Atsushi Okada, Makoto Amaki, Hiroyuki Takahama, Yasuo Sugano, Hideaki Kanzaki, Satoshi Yasuda, Toshihisa Anzai, Chisato Izumi
Circulation reports, 1, 1, 42, 42, 15 Dec. 2018, [Domestic magazines]
English, Scientific journal

A Case of Severe Aortic Regurgitation Caused by Takayasu's Arteritis Showing End-Diastolic Opening of Aortic Valve.
Michito Murayama, Hiroyuki Iwano, Yusuke Kudo, Mutsumi Nishida, Koji Akizawa, Hitoshi Shibuya, Toshihisa Anzai
CASE (Philadelphia, Pa.), 2, 6, 248, 253, Dec. 2018, [Peer-reviewed], [International Magazine]
English

Left ventricular noncompaction with intractable heart failure responsive to empagliflozin.
Yasuyuki Chiba, Kazuya Yonezawa, Masahumi Himeno, Midori Yukino, Kyo Shimazu, Shogo Imagawa, Kaoru Komuro, Noriko Kimura, Teisuke Anzai, Toshihisa Anzai
Journal of cardiology cases, 18, 6, 192, 196, Dec. 2018, [Peer-reviewed], [Domestic magazines]
English, Despite several reports on the mechanism of the effect of empagliflozin, which has the potential for improved prognosis in heart failure, it is still not fully understood. We experienced a case of left ventricular noncompaction that caused fluid retention in a patient who showed resistance to existing diuretics. By using empagliflozin, we successfully treated this case of acute heart failure and observed stabilized symptoms with no renal dysfunction and deterioration of patient condition. Although the potential for improved prognosis with this drug in a high-risk group for cardiovascular events has been reported, based on EMPA-REG OUTCOME trial results, there are few reports on its effect of treatment and mechanism in treating acute heart failure. The effect of this drug in treating heart failure from the acute phase to the chronic phase can be expected. .

Refractory cardiac myocarditis associated with drug rash with eosinophilia and systemic symptoms syndrome due to anti-bipolar disorder drugs: a case report.
Hikaru Hagiwara, Arata Fukushima, Hiroyuki Iwano, Toshihisa Anzai
European heart journal. Case reports, 2, 4, yty100, Dec. 2018, [Peer-reviewed], [International Magazine]
English, Background: Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse drug reaction accompanied by multiple organ dysfunction. Myocarditis is a manifestation, and once acute necrotizing eosinophilic myocarditis (ANEM) develops, the mortality rate is high. Case summary: We report the case of a 37-year-old man who developed myocarditis associated with DRESS syndrome after starting treatment with lithium and quetiapine for bipolar disorder. At that time, he presented with fever, morbilliform eruption, lymphadenopathy, eosinophilia with atypical lymphocytes, and liver dysfunction; bipolar drugs were discontinued and oral prednisolone begun. Four months later, he was admitted to our institution with worsening skin rash and dyspnoea. Transthoracic echocardiography revealed reduced systolic function in both ventricles, and endocardial biopsy indicated hypersensitivity myocarditis. Cardiac function was temporarily normalized by high-dose prednisolone. However, the inflammation was persistent as shown by a re-elevation of troponin T and fall of left ventricular ejection fraction several months later; in addition, 18F-fluoro-deoxyglucose positron emission tomography with chest computed tomography (FDG-PET/CT) showed focal FDG uptake in the left ventricle. Despite additional treatment with mycophenolate mofetil, the cardiac function deteriorated further, and the patient eventually manifested refractory heart failure classified as New York Heart Association (NYHA) Class III. Myocardial biopsy showed myocyte necrosis associated with ANEM. Discussion: This is the first case report of DRESS-associated myocarditis due to treatment for bipolar disorder. Although the pathophysiology remains incompletely understood, lithium and/or quetiapine can induce refractory myocarditis in DRESS syndrome. Regular measurements of troponin T and FDG-PET/CT are useful for assessing disease progression in DRESS-associated myocarditis.

Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis Complicated by Sigmoid Septum.
Kizuku Yamashita, Tomoyuki Fujita, Satsuki Fukushima, Yusuke Shimahara, Yuta Kume, Yorihiko Matsumoto, Naonori Kawamoto, Kimito Minami, Daijiro Kabata, Hideaki Kanzaki, Chisato Izumi, Toshihisa Anzai, Junjiro Kobayashi
Circulation journal : official journal of the Japanese Circulation Society, 82, 12, 3090, 3099, 24 Nov. 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: In patients undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS), a sigmoid septum, characterized by subaortic interventricular hypertrophy, often results in the need for new pacemaker implantation (PMI). In this study, we reviewed the feasibility and treatment efficacy of TAVR for AS in patients with a sigmoid septum. Methods and Results: Between 2011 and 2016, 48 patients (25.4%; mean age 84.9±5.4 years; 9 males) with a sigmoid septum and 141 (74.6%; mean age 82.9±5.5 years; 61 males) without underwent TAVR. Their operative outcomes, echocardiographic and electrocardiographic findings, and long-term outcomes were retrospectively compared. Second TAVR because of valve malposition was performed in 3 patients with a sigmoid septum (6.3%) and in 2 patients without a sigmoid septum (1.4%), with no significant difference between the 2 groups. Although there was no significant difference in valve hemodynamics between the 2 groups, sigmoid septum and deep implantation (implantation depth ≥10 mm) were independent predictors of new PMI following TAVR. CONCLUSIONS: Although a sigmoid septum did not preclude the feasibility, safety, or efficacy of TAVR for severe AS, its presence was associated with new PMI. Our approach to TAVR in patients with a sigmoid septum may contribute to clinical outcomes comparable to those of patients without this pathology.

Peripartum Serial Echocardiographic Findings in a Patient with Life-threatening Peripartum Cardiomyopathy.
Daisetsu Aoyama, Yasuhiro Hamatani, Chizuko Kamiya, Keiko Ohta-Ogo, Makoto Amaki, Shoji Kawakami, Atsushi Okada, Hiroyuki Takahama, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 57, 21, 3105, 3109, 01 Nov. 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, A 35-year-old woman was referred to our hospital for the management of acutely decompensated heart failure due to peripartum cardiomyopathy (PPCM). Generally, cardiac examinations are performed after the manifestation of heart failure in patients with PPCM. Thus, reports of serial cardiac examinations before the onset of PPCM are scarce. In this case, we were able to document the serial echocardiographic findings before the onset of life-threatening PPCM. We found that the left ventricular systolic function was preserved at 35 weeks of gestation but declined acutely after delivery at 38 weeks. Although speculative, these findings suggest that left ventricular dilation might precede the onset of PPCM.

A case of medical management of tricuspid regurgitation related to atrial fibrillation with constrictive pericarditis-like hemodynamics.
Yoshiya Kato, Arata Fukushima, Hiroyuki Iwano, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai
Journal of cardiology cases, 18, 5, 175, 179, Nov. 2018, [Peer-reviewed], [Domestic magazines]
English, Severe tricuspid regurgitation (TR) is reported to represent a hemodynamic pattern similar to that of constrictive pericarditis (CP), which should be clearly differentiated for appropriate management. We report the case of a patient with severe TR due to atrial fibrillation (AF) in whom hemodynamic monitoring played a role in the selection of the management strategy. An 81-year-old Japanese man with chronic AF was admitted due to worsening heart failure. Echocardiography showed the dilation of bilateral atria and a right ventricle with severe TR. The right heart catheterization demonstrated the elevation and equalization of diastolic pressures of four cardiac chambers with impaired diastolic filling pattern, which are hallmarks of pericardial constriction due to CP. Of note, the CP-like hemodynamics were completely normalized by 10 days of medical therapies including diuretics and carperitide. After his discharge and over a 1-year follow-up, he has never experienced worsening heart failure and remained NYHA class II with moderate TR. Medical management targeted at volume reduction and vasodilation can be a therapeutic option for CP-like hemodynamics in isolated severe TR related to AF. Repeated hemodynamic assessment is an appropriate tool to help our understanding of the CP-like physiology caused by severe TR based on chronic AF. .

Brain-Derived Neurotrophic Factor Improves Limited Exercise Capacity in Mice With Heart Failure.
Junichi Matsumoto, Shingo Takada, Shintaro Kinugawa, Takaaki Furihata, Hideo Nambu, Naoya Kakutani, Masaya Tsuda, Arata Fukushima, Takashi Yokota, Shinya Tanaka, Hidehisa Takahashi, Masashi Watanabe, Shigetsugu Hatakeyama, Masaki Matsumoto, Keiichi I Nakayama, Yutaro Otsuka, Hisataka Sabe, Hiroyuki Tsutsui, Toshihisa Anzai
Circulation, 138, 18, 2064, 2066, 30 Oct. 2018, [Peer-reviewed], [International Magazine]
English

Impact of High Respiratory Exchange Ratio During Submaximal Exercise on Adverse Clinical Outcome in Heart Failure.
Naoya Kakutani, Arata Fukushima, Takashi Yokota, Takashi Katayama, Hideo Nambu, Ryosuke Shirakawa, Satoshi Maekawa, Takahiro Abe, Shingo Takada, Takaaki Furihata, Kota Ono, Koichi Okita, Shintaro Kinugawa, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 82, 11, 2753, 2760, 25 Oct. 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: Oxygen uptake (V̇O2) at peak workload and anaerobic threshold (AT) workload are often used for grading heart failure (HF) severity and predicting all-cause mortality. The clinical relevance of respiratory exchange ratio (RER) during exercise, however, is unknown. Methods and Results: We retrospectively studied 295 HF patients (57±15 years, NYHA class I-III) who underwent cardiopulmonary exercise testing. RER was measured at rest; at AT workload; and at peak workload. Peak V̇O2 had an inverse correlation with RER at AT workload (r=-0.256), but not at rest (r=-0.084) or at peak workload (r=0.090). Using median RER at AT workload, we divided the patients into high RER (≥0.97) and low RER (<0.97) groups. Patients with high RER at AT workload were characterized by older age, lower body mass index, anemia, and advanced NYHA class. After propensity score matching, peak V̇O2 tended to be lower in the high-RER than in the low-RER group (14.9±4.5 vs. 16.1±5.0 mL/kg/min, P=0.06). On Kaplan-Meier analysis, HF patients with a high RER at AT workload had significantly worse clinical outcomes, including all-cause mortality and rate of readmission due to HF worsening over 3 years (29% vs. 15%, P=0.01). CONCLUSIONS: High RER during submaximal exercise, particularly at AT workload, is associated with poor clinical outcome in HF patients.

Which is the proper reference tissue for measuring the change in FDG PET metabolic volume of cardiac sarcoidosis before and after steroid therapy?
Sho Furuya, Osamu Manabe, Hiroshi Ohira, Kenji Hirata, Tadao Aikawa, Masanao Naya, Ichizo Tsujino, Kazuhiro Koyanagawa, Toshihisa Anzai, Noriko Oyama-Manabe, Tohru Shiga
EJNMMI research, 8, 1, 94, 94, 05 Oct. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Cardiac sarcoidosis (CS) is a rare but potentially life-threatening disease that causes conduction disturbance, systolic dysfunction, and, most notably, sudden cardiac death. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) plays important roles not only in diagnosing CS but also in evaluating the effects of anti-inflammatory therapy. A volume-based analysis of parameters measured by FDG PET, so-called cardiac metabolic volume (CMV), has emerged as a new assessment tool. CMV is measured as the volume within the boundary determined by a reference tissue such as the liver and the blood pool uptake. However, there is a possibility that oral steroid therapy could lead to variations of the liver and the blood pool uptake. Here, we attempted to evaluate the steroid effects on the liver and the blood pool uptake. A total of 38 CS patients who underwent FDG PET/CT before and during steroid therapy were retrospectively enrolled. Volumes of interest (VOIs) were placed in the right lobe of the liver and descending aorta (DA). The maximum standardized uptake value (SUVmax), SUVmean, and SUVpeak of the liver and DA were compared between time points before and during steroid therapy. RESULTS: The SUVmax, SUVmean, and SUVpeak of the liver during steroid therapy significantly increased from the time point before the therapy (SUVmax 3.5 ± 0.4 vs. 3.8 ± 0.6, p = 0.014; SUVmean 2.7 ± 0.3 vs. 3.0 ± 0.5, p = 0.0065; SUVpeak 3.0 ± 0.4 vs. 3.4 ± 0.6, p = 0.006). However, the SUVmax, SUVmean, and SUVpeak in the DA did not significantly change (SUVmax 2.2 ± 0.3 vs. 2.2 ± 0.4, p = 0.46; SUVmean 1.9 ± 0.3 vs. 2.0 ± 0.4, p = 0.56; SUVpeak 2.0 ± 0.3 vs. 2.0 ± 0.3, p = 0.70). CONCLUSIONS: We measured FDG uptake in the liver and blood pool before and during steroid therapy. Steroid therapy increased the liver uptake but not the blood pool uptake. Our findings suggested that the DA uptake is a more suitable threshold than liver uptake to evaluate therapeutic effects using volume-based analysis of cardiac FDG PET.

Protein acetylation in skeletal muscle mitochondria is involved in impaired fatty acid oxidation and exercise intolerance in heart failure.
Masaya Tsuda, Arata Fukushima, Junichi Matsumoto, Shingo Takada, Naoya Kakutani, Hideo Nambu, Katsuma Yamanashi, Takaaki Furihata, Takashi Yokota, Koichi Okita, Shintaro Kinugawa, Toshihisa Anzai
Journal of cachexia, sarcopenia and muscle, 9, 5, 844, 859, Oct. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Exercise intolerance is a common clinical feature and is linked to poor prognosis in patients with heart failure (HF). Skeletal muscle dysfunction, including impaired energy metabolism in the skeletal muscle, is suspected to play a central role in this intolerance, but the underlying mechanisms remain elusive. Lysine acetylation, a recently identified post-translational modification, has emerged as a major contributor to the derangement of mitochondrial metabolism. We thus investigated whether mitochondrial protein acetylation is associated with impaired skeletal muscle metabolism and lowered exercise capacity in both basic and clinical settings of HF. METHODS: We first conducted a global metabolomic analysis to determine whether plasma acetyl-lysine is a determinant factor for peak oxygen uptake (peak VO2 ) in HF patients. We then created a murine model of HF (n = 11) or sham-operated (n = 11) mice with or without limited exercise capacity by ligating a coronary artery, and we tested the gastrocnemius tissues by using mass spectrometry-based acetylomics. A causative relationship between acetylation and the activity of a metabolic enzyme was confirmed in in vitro studies. RESULTS: The metabolomic analysis verified that acetyl-lysine was the most relevant metabolite that was negatively correlated with peak VO2 (r = -0.81, P < 0.01). At 4 weeks post-myocardial infarction HF, a treadmill test showed lowered work (distance × body weight) and peak VO2 in the HF mice compared with the sham-operated mice (11 ± 1 vs. 23 ± 1 J, P < 0.01; 143 ± 5 vs. 159 ± 3 mL/kg/min, P = 0.01; respectively). As noted, the protein acetylation of gastrocnemius mitochondria was 48% greater in the HF mice than the sham-operated mice (P = 0.047). Acetylproteomics identified the mitochondrial enzymes involved in fatty acid β-oxidation (FAO), the tricarboxylic acid cycle, and the electron transport chain as targets of acetylation. In parallel, the FAO enzyme (β-hydroxyacyl CoA dehydrogenase) activity and fatty acid-driven mitochondrial respiration were reduced in the HF mice. This alteration was associated with a decreased expression of mitochondrial deacetylase, Sirtuin 3, because silencing of Sirtuin 3 in cultured skeletal muscle cells resulted in increased mitochondrial acetylation and reduced β-hydroxyacyl CoA dehydrogenase activity. CONCLUSIONS: Enhanced mitochondrial protein acetylation is associated with impaired FAO in skeletal muscle and reduced exercise capacity in HF. Our results indicate that lysine acetylation is a crucial mechanism underlying deranged skeletal muscle metabolism, suggesting that its modulation is a potential approach for exercise intolerance in HF.

Japanese Antibacterial Drug Management for Cardiac Sarcoidosis (J-ACNES): A multicenter, open-label, randomized, controlled study.
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, Oct. 2018, [Peer-reviewed], [Domestic magazines]
English, 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.

Long-term reliability of the defibrillator lead inserted by the extrathoracic subclavian puncture.
Masaya Watanabe, Hisashi Yokoshiki, Hirofumi Mitsuyama, Kazuya Mizukami, Taro Tenma, Rui Kamada, Masayuki Takahashi, Yoshiro Matsui, Toshihisa Anzai
Journal of arrhythmia, 34, 5, 541, 547, Oct. 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Background: As the transvenous defibrillator lead is fragile and its failure may cause a life-threatening event, reliable insertion techniques are required. While the extrathoracic puncture has been introduced to avoid subclavian crush syndrome, the reports on the long-term defibrillator lead survival using this approach, especially the comparison with the cephalic cutdown (CD), remain scarce. We aimed to evaluate the long-term survival of the transvenous defibrillator lead inserted by the extrathoracic subclavian puncture (ESCP) compared with CD. Methods: Between 1998 and 2011, 324 consecutive patients who underwent an implantable cardioverter-defibrillator (ICD) implantation in Hokkaido University Hospital were included. ICD leads were inserted by CD from 1998 to 2003 and by contrast venography-guided ESCP thereafter. Lead failure was defined as a nonphysiologic high-rate oversensing with abnormal lead impedance or highly elevated sensing and pacing threshold. Results: Of 324 patients, CD was used in 37 (11%) and ESCP in 287 patients (89%). During the median follow-up of 6.2 years (IQR:3.2-8.3), 7 leads (2 in CD and 5 leads in ESCP group) failed. All patients with lead failure in ESCP group were implanted with either SJM Riata (n = 1) or Medtronic Fidelis lead (n = 4). Five-year lead survival was 93.8% (CI95%:77.3-98.4%) in CD compared with 99.1% (CI95%:96.6-99.8%) in ESCP group (P = 0.903). Univariate Cox regression analysis showed that the use of Fidelis or Riata lead was the strong predictor of the ICD lead failure (HR 13.8, CI95%:2.9-96.5; P = 0.001). Conclusions: Contrast venography-guided extrathoracic puncture ensures the reliable long-term survival in the transvenous defibrillator leads.

The first multicenter, randomized, controlled trial of home telemonitoring for Japanese patients with heart failure: home telemonitoring study for patients with heart failure (HOMES-HF)
Norihiko Kotooka, Masafumi Kitakaze, Kengo Nagashima, Machiko Asaka, Yoshiharu Kinugasa, Kotaro Nochioka, Atsushi Mizuno, Daisuke Nagatomo, Daigo Mine, Yoko Yamada, Akiko Kuratomi, Norihiro Okada, Daisuke Fujimatsu, So Kuwahata, Shigeru Toyoda, Shin ichi Hirotani, Takahiro Komori, Kazuo Eguchi, Kazuomi Kario, Takayuki Inomata, Kaoru Sugi, Kazuhiro Yamamoto, Hiroyuki Tsutsui, Tohru Masuyama, Hiroaki Shimokawa, Shin ichi Momomura, Yoshihiko Seino, Yasunori Sato, Teruo Inoue, Koichi Node, Mika Nakamizo, Chika Nishiyama, Kikumi Morita, Yuko Horiuchi, Michiko Hanawa, Takako Kanai, Hideki Hanaoka, Tohru Izumi, Yoshihiko Saito, Yukihito Sato, A. Haruyama, S. Inami, Y. Nishi, A. Amano, T. Arikawa, M. Kikuchi, Y. Eto, K. Ishii, K. Fukuda, S. Soejima, R. Hisano, D. Goto, S. Kinugawa, Y. Naito, A. Goda, T. Iwasaku, A. Eguchi, Y. Okuhara, R. Taniguchi, Y. Takatsu, K. Washida, T. Miyamoto, M. Toma, K. Yoshitani, R. Fukuhara, H. Fujiwara, K. Matsunaga, T. Iwata, Y. Nishimura, S. Hoshide, M. Shinpo, K. Kario, T. Katsuya, S. Katsuya, T. Naruke, M. Kiryu, S. Kurokawa, T. Sato, T. Koitabashi, M. Kajiwara, Y. Hiramatsu, Y. Sedutsu, T. Hashimoto, U. Yamamoto, K. Miyata, M. Mohri, H. Yamamoto, H. Origuchi, T. Hasegawa, A. Funada, H. Takahama, T. Ohara, H. Kanzaki, M. Asakura, T. Noguchi, Y. Goto, T. Anzai, C. Ibuki, T. Oba, M. Takano
Heart and Vessels, 33, 8, 866, 876, 01 Aug. 2018, [Peer-reviewed]
English, Scientific journal

Clinical determinants of successful weaning from extracorporeal membrane oxygenation in patients with fulminant myocarditis.
Manabu Matsumoto, Yasuhide Asaumi, Yuichi Nakamura, Takeshi Nakatani, Toshiyuki Nagai, Tomoaki Kanaya, Shoji Kawakami, Satoshi Honda, Yu Kataoka, Seiko Nakajima, Osamu Seguchi, Masanobu Yanase, Kunihiro Nishimura, Yoshihiro Miyamoto, Kengo Kusano, Toshihisa Anzai, Teruo Noguchi, Tomoyuki Fujita, Junjiro Kobayashi, Hatsue Ishibashi-Ueda, Hiroaki Shimokawa, Satoshi Yasuda
ESC heart failure, 5, 4, 675, 684, Aug. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIMS: Patients with fulminant myocarditis (FM) often present with cardiogenic shock and require mechanical circulatory support, including extracorporeal membrane oxygenation (ECMO) and ventricular assist device (VAD) implantation. This study sought to clarify the determinants of successful weaning from ECMO in FM patients. METHODS AND RESULTS: We studied 37 consecutive FM patients supported by ECMO as the initial form of mechanical circulatory support between January 1995 and December 2014 in our hospital. Twenty-two (59%) patients were successfully weaned from ECMO, while 15 (41%) were not. There were significant differences in levels of peak creatine kinase and those of its MB isoform (CK-MB), left ventricular posterior wall thickness (LVPWT), and prevalence of cardiac rhythm disturbances. Receiver operating characteristic curve analysis revealed that a peak CK-MB level of 185 IU/L and LVPWT of 11 mm were the optimal cut-off values for predicting successful weaning from ECMO (areas under the curve, 0.89 and 0.85, respectively). During the follow-up [median 48 (interquartile range 8-147) months], 83% of FM patients who were weaned from ECMO survived, with preserved fractional shortening based on echocardiography. Of the 15 FM patients who were not weaned from ECMO, nine bridged to VAD, and only two were successfully weaned from VAD and survived. CONCLUSIONS: These results indicate that myocardial injury, as evidenced by CK-MB and LVPWT, and prolonged presence of cardiac rhythm disturbances are important clinical determinants of successful weaning from ECMO.

Validation of U.S. mortality prediction models for hospitalized heart failure in the United Kingdom and Japan.
Toshiyuki Nagai, Varun Sundaram, Ahmad Shoaib, Yasuyuki Shiraishi, Shun Kohsaka, Kieran J Rothnie, Susan Piper, Theresa A McDonagh, Suzanna M C Hardman, Ayumi Goda, Atsushi Mizuno, Mitsuaki Sawano, Alan S Rigby, Jennifer K Quint, Tsutomu Yoshikawa, Andrew L Clark, Toshihisa Anzai, John G F Cleland
European journal of heart failure, 20, 8, 1179, 1190, Aug. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIMS: Prognostic models for hospitalized heart failure (HHF) were developed predominantly for patients of European origin in the United States of America; it is unclear whether they perform similarly in other health care systems or for different ethnicities. We sought to validate published prediction models for HHF in the United Kingdom (UK) and Japan. METHODS AND RESULTS: Patients in the UK (n =894) and Japan (n =3158) were prospectively enrolled and were similar in terms of sex (∼60% men) and median age (∼77 years). Models predicted that British patients would have a higher mortality than Japanese, which was indeed true both for in-hospital (4.8% vs. 2.5%) and 180-day (20.7% vs. 9.5%) mortality. The model c-statistics for the published/derivation (range 0.70-0.76) and Japanese (range 0.75-0.77) cohorts were similar and higher than for the UK (0.62-0.75) but models consistently overestimated mortality in Japan. For in-hospital mortality, the OPTIMIZE-HF model performed best, providing similar discrimination in published/derivation, UK and Japanese cohorts [c-indices: 0.75 (0.74-0.77); 0.75 (0.68-0.81); and 0.77 (0.70-0.83), respectively], and least overestimated mortality in Japan. For 180-day mortality, the c-statistics for the ASCEND-HF model were similar in published/derivation (0.70) and UK [0.69 (0.64-0.74)] cohorts but higher in Japan [0.75 (0.71-0.79)]; calibration was good in the UK but again overestimated mortality in Japan. CONCLUSION: Calibration of published prediction models appears moderately accurate and unbiased when applied to British patients but consistently overestimates mortality in Japan. Identifying the reason why patients in Japan have a better than predicted prognosis is of great interest.

Rationale and Design of the Multicenter Trial on Japan Working Group on the Effects of Angiotensin Receptor Blockers Selection (Azilsartan vs. Candesartan) on Diastolic Function in the Patients Suffering from Heart Failure with Preserved Ejection Fraction: J-TASTE Trial.
Hiroyuki Takahama, Masanori Asakura, Yukio Abe, Masayoshi Ajioka, Kazutaka Aonuma, Toshihisa Anzai, Takaharu Hayashi, Shinya Hiramitsu, Hiroya Kawai, Hidetaka Kioka, Kazuo Kimura, Young-Jae Lim, Ken Matsuoka, Hirohiko Motoki, Yoji Nagata, Sunao Nakamura, Nobuyuki Ohte, Yukio Ozaki, Taishi Sasaoka, Shunsuke Tamaki, Toshimitsu Hamasaki, Masafumi Kitakaze
Cardiovascular drugs and therapy, 32, 4, 381, 388, Aug. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Previous studies suggest that the pathophysiology of heart failure with preserved ejection fraction (HFpEF) is characterized not only by high ventricular stiffness, but also by vascular stiffness. Azilsartan has higher vascular affinity compared with other angiotensin II receptor blockers (ARBs), which were proven to have no beneficial effects on clinical outcomes in patients with HFpEF in earlier clinical trials. We aimed to test the hypothesis that azilsartan may improve left ventricular diastolic function in HFpEF patients with hypertension in this trial. METHODS: The Effects of Angiotensin Receptor Blockers on Diastolic Function in Patients Suffering from Heart Failure with Preserved Ejection Fraction: J-TASTE trial is a multicenter, randomized, open-labeled, and assessor(s)-blinded, active controlled using candesartan, parallel-group clinical trial, to compare changes in left ventricular (LV) diastolic dysfunction between HFpEF patients with hypertension who have received candesartan or azilsartan for 48 weeks. The primary endpoint is the change in early diastolic wave height/early diastolic mitral annulus velocity (E/e') assessed by echocardiography from the baseline to the end of the study (48 weeks). A total of 190 patients will be recruited into the study. CONCLUSIONS: The design of the J-TASTE trial will provide data on whether differences between the effects of the two tested drugs on LV diastolic function exist in HFpEF patients with hypertension and will improve understanding of the pathophysiological role of vascular stiffness on diastolic function.

Mitral Regurgitation and Heart Failure as the First Presentation in a Patient with Features of Two Connective Tissue Disorders: A Rare Combination of Mucopolysaccharidosis and Osteogenesis Imperfecta?
Yasuhiro Hamatani, Junko Nakashima, Keiko Ohta-Ogo, Makoto Amaki, Masashi Koga, Daisetsu Aoyama, Kyohei Marume, Kenichiro Sawada, Yasuteru Nakashima, Atsushi Shibata, Atsushi Okada, Hiroyuki Takahama, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Yoshihiko Ikeda, Satoshi Yasuda, Hatsue Ishibashi-Ueda, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 57, 15, 2209, 2215, 01 Aug. 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Connective tissue disorders sometimes involve cardiovascular systems. This report describes the case of a middle-aged man with mitral regurgitation and heart failure. He had distinctive features of mucopolysaccharidosis type (MPS) III, but no gene mutations that were known to be associated with MPS. Meanwhile, he had a COL1A2 gene mutation that is associated with osteogenesis imperfecta (OI), and had some features that were compatible with OI. The patient might have had a rare connective tissue disorder with the characteristics of MPS III and OI, which was initially detected as a result of the cardiovascular manifestations.

Performance of the MAGGIC heart failure risk score and its modification with the addition of discharge natriuretic peptides.
Mitsuaki Sawano, Yasuyuki Shiraishi, Shun Kohsaka, Toshiyuki Nagai, Ayumi Goda, Atsushi Mizuno, Yasumori Sujino, Yuji Nagatomo, Takashi Kohno, Toshihisa Anzai, Keiichi Fukuda, Tsutomu Yoshikawa
ESC heart failure, 5, 4, 610, 619, Aug. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIMS: Predictive models for heart failure patients are widely used in the clinical practice to stratify patients' mortality and enable clinicians to tailor and intensify their approach. However, such models have not been validated internationally. In addition, biomarkers are now frequently measured to obtain prognostic information, and the implications of this practice are not known. In this study, we aimed to validate the model performance of the Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) score in a Japanese acute heart failure registry and further explore the incremental prognostic value of discharge B-type natriuretic peptide (BNP) level. METHODS AND RESULTS: In this study, we evaluated the registered data of 2215 consecutive acute HF patients (with 694 119 person-years follow-up) from a prospective multicentre registry (the West Tokyo Heart Failure) conducted in Japan from April 2006 to August 2016. The mean age was 73.0 ± 13.0, and 61.2% were male. The MAGGIC score demonstrated modest discrimination (c-index = 0.71, 95% confidence interval 0.67-0.74) and good calibration (R2 value = 0.97); there was constant overestimation for 1 year mortality. However, when the BNP level was added to the original MAGGIC variables, the model demonstrated good discrimination (c-index = 0.74, 95% confidence interval 0.70-0.78) with adequate calibration (R2 value = 0.91). The modified MAGGIC BNP score was externally validated in a separate Japanese registry (NaDEF) and demonstrated moderate discrimination (c-index = 0.69, 95% confidence interval 0.65-0.73) and calibration (R2 value = 0.85). CONCLUSION: The original MAGGIC score performed modestly in Japanese patients, but the addition of discharge BNP level enhanced model performance. The addition of objective biomarkers may result in effective modification of preexisting internationally recognized risk models and aid in multinational comparisons of heart failure patients' outcomes.

Left ventricular myxoma with Carney complex.
Naoto Kuyama, Yasuhiro Hamatani, Satsuki Fukushima, Yoshihiko Ikeda, Eri Nakai, Atsushi Okada, Hiroyuki Takahama, Makoto Amaki, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Tomoyuki Fujita, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Toshihisa Anzai, Junjiro Kobayashi
ESC heart failure, 5, 4, 713, 715, Aug. 2018, [Peer-reviewed], [International Magazine]
English, The left ventricle is a less frequent location of cardiac myxomas overall. Meanwhile, cardiac myxomas related to Carney complex (CNC), which is a multiple neoplasia syndrome involving cardiac, endocrine, neural, and cutaneous tumours, more frequently occur in the left ventricle compared with sporadic cardiac myxomas. Herein, we report a case of a 20-year-old woman with CNC who underwent complete surgical excision of a large and mobile left ventricular myxoma. In our case, echocardiography performed 4 years earlier was normal. This case highlights the importance of annual follow-up by echocardiography in patients with CNC, because early diagnosis of cardiac myxomas might improve their prognosis. Besides, we should bear in mind the possibility of CNC if the patients have cardiac myxoma in a cardiac chamber other than the left atrium at a younger age.

Elevated Plasma D-Dimer Level Is Associated With Short-Term Risk of Ischemic Stroke in Patients With Acute Heart Failure.
Yasuhiro Hamatani, Toshiyuki Nagai, Michikazu Nakai, Kunihiro Nishimura, Yasuyuki Honda, Hiroki Nakano, Satoshi Honda, Naotsugu Iwakami, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Kazunori Toyoda, Satoshi Yasuda, Hiroyuki Yokoyama, Hisao Ogawa, Toshihisa Anzai
Stroke, 49, 7, 1737, 1740, Jul. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND AND PURPOSE: The incidence of heart failure increases the subsequent risk of ischemic stroke, and its risk could be higher in the short-term period after an acute heart failure (AHF) event. However, its determinants remain to be clarified. Plasma D-dimer level reflects fibrin turnover and exhibits unique properties as a biomarker of thrombosis. The aim of this study is to investigate whether D-dimer level is a determinant of short-term incidence of ischemic stroke in patients with AHF. METHODS: We examined 721 consecutive hospitalized AHF patients with plasma D-dimer level on admission from our prospective registry between January 2013 and May 2016. The study end points were incidence of ischemic stroke during hospitalization and at 30 days after admission. RESULTS: Of the total participants (mean age, 76 years; male, 60%; atrial fibrillation, 54%; mean left ventricular ejection fraction, 38%), in-hospital ischemic stroke occurred in 18 patients (2.5%) during a median hospitalization period of 21 days, and 30-day ischemic stroke occurred in 16 patients (2.2%). Higher D-dimer level on admission was an independent determinant of subsequent risk of in-hospital ischemic stroke even after adjustment by CHA2DS2-VASc score (odds ratio, 2.29; 95% confidence interval, 1.46-3.60; P<0.001) or major confounders, including age, atrial fibrillation, and antithrombotic therapy (odds ratio, 2.31; 95% confidence interval, 1.43-3.74; P<0.001). Subgroup analyses showed consistent findings in patients without atrial fibrillation (odds ratio, 2.46; 95% confidence interval, 1.39-4.54; P=0.002) and those without antithrombotic therapy (odds ratio, 2.79; 95% confidence interval, 1.53-5.57; P<0.001). Similar results were obtained for 30-day ischemic stroke as an alternative outcome. CONCLUSIONS: Elevated plasma D-dimer level on admission was significantly associated with increased incidence of ischemic stroke shortly after admission for AHF, suggesting a predictive role of D-dimer for short-term ischemic stroke events in patients with AHF. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000017024.

Impact of iron deficiency on long-term clinical outcomes of hospitalized patients with heart failure.
Hiroki Nakano, Toshiyuki Nagai, Varun Sundaram, Michikazu Nakai, Kunihiro Nishimura, Yasuyuki Honda, Satoshi Honda, Naotsugu Iwakami, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Hisao Ogawa, Satoshi Yasuda, Taishiro Chikamori, Toshihisa Anzai
International journal of cardiology, 261, 114, 118, 15 Jun. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Iron deficiency (ID) is commonly observed in chronic heart failure (HF) patients and is associated with worse clinical outcomes. While ID is frequent finding in hospitalized heart failure (HHF), its impact on long-term outcome in HHF patients remains unclear. METHODS: We evaluated iron status at discharge in 578 HHF patients. Absolute ID was defined as serum ferritin <100 μg/L, and functional ID (FID) was defined as serum ferritin of 100-299 μg/L with transferrin saturation <20%. The primary outcome of interest was the composite of all-cause mortality and HF admission at one year. RESULTS: Among the study population, 185 had absolute ID, 88 had FID and 305 had no evidence of ID. At one-year post-discharge, 64 patients had died and 112 had been readmitted with HF. Patients with absolute ID had more adverse events than those with FID or no ID (p = 0.021). In multivariate Cox regression analyses, absolute ID was significantly associated with increased risk of adverse events at one year (HR 1.50, 95% CI 1.02-2.21, p = 0.040) compared with the remaining patients. Sensitivity analysis revealed that its prognostic effect did not differ across anemic status, or between HF with reduced and preserved ejection fraction (p for interaction = 0.17, 0.68, respectively). CONCLUSION: Absolute ID, but not FID, at discharge was associated with increased risk of one-year mortality or HF admission in patients with HHF. Further studies are required to evaluate the role of repleting iron stores and its impact on clinical outcomes in patients with HHF.

Clinical Utility of Echocardiographic Hemodynamic Monitoring during Manual Compression of Arteriovenous Shunt in a Patient with High-Output Heart Failure.
Hiroyuki Iwano, Shingo Tsujinaga, Daiki Iwami, Naoya Asakawa, Satoshi Yamada, Toshihisa Anzai
CASE (Philadelphia, Pa.), 2, 3, 103, 108, Jun. 2018, [Peer-reviewed], [International Magazine]
English

Clinical Characteristics, Management, and Outcomes of Japanese Patients Hospitalized for Heart Failure With Preserved Ejection Fraction - A Report From the Japanese Heart Failure Syndrome With Preserved Ejection Fraction (JASPER) Registry.
Toshiyuki Nagai, Tsutomu Yoshikawa, Yoshihiko Saito, Yasuchika Takeishi, Kazuhiro Yamamoto, Hisao Ogawa, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 82, 6, 1534, 1545, 25 May 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: Despite the specific characteristics of heart failure with preserved ejection fraction (HFpEF) having been demonstrated predominantly from registries in Western countries, important international differences exist in terms of patient characteristics, management and medical infrastructure between Western and Asian countries.Methods and Results:We performed nationwide registration of consecutive Japanese hospitalized HFpEF patients with left ventricular EF ≥50% from 15 sites between November 2012 and March 2015. Follow-up data were obtained up to 2 years post-discharge. A total of 535 patients were registered. The median age was 80 years and 50% were female. The most common comorbid conditions were hypertension (77%) and atrial fibrillation (AF: 62%), but body mass index was relatively low. In-hospital mortality rate was 1.3% and the median length of hospitalization was 16 days. By 2 years post-discharge, 40.8% of patients had all-cause death or HF hospitalization. Approximately one-half of deaths had a cardiac cause. Lower serum albumin on admission was one of the strongest independent determinants of worse clinical outcome. CONCLUSIONS: Japanese HFpEF patients were less obese, but had a substantially higher prevalence of AF and lower incidence of subsequent events compared with previous reports. Our findings indicated that specific preventative and therapeutic strategies focusing on AF and nutritional status might need to be considered for Japanese hospitalized patients with HFpEF.

Subacute Left Atrial Thrombus Formation After Percutaneous Edge-to-Edge Mitral Valve Repair for Functional Mitral Regurgitation.
Makoto Amaki, Yu Kataoka, Hideaki Kanzaki, Koji Miyamoto, Atsushi Okada, Yasuhiro Hamatani, Masashi Fujino, Hiroyuki Takahama, Takuya Hasegawa, Yasuo Sugano, Kengo Kusano, Yoshihiko Ohnishi, Tomoyuki Fujita, Junjiro Kobayashi, Toshihisa Anzai, Satoshi Yasuda
Circulation journal : official journal of the Japanese Circulation Society, 82, 6, 1712, 1713, 25 May 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Relation between total shock energy and mortality in patients with implantable cardioverter-defibrillator.
Taro Tenma, Hisashi Yokoshiki, Hirofumi Mitsuyama, Masaya Watanabe, Kazuya Mizukami, Rui Kamada, Masayuki Takahashi, Ryo Sasaki, Motoki Maeno, Kaori Okamoto, Yuki Chiba, Toshihisa Anzai
International journal of cardiology, 259, 94, 99, 15 May 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Implantable Cardioverter-Defibrillator (ICD) shocks have been associated with mortality. However, no study has examined the relation between total shock energy and mortality. The aim of this study is to assess the association of total shock energy with mortality, and to determine the patients who are at risk of this association. METHODS: Data from 316 consecutive patients who underwent initial ICD implantation in our hospital between 2000 and 2011 were retrospectively studied. We collected shock energy for 3 years from the ICD implantation, and determined the relation of shock energy on mortality after adjusting confounding factors. RESULTS: Eighty-seven ICD recipients experienced shock(s) within 3 years from ICD implantation and 43 patients had died during the follow-up. The amount of shock energy was significantly associated with all-cause death [adjusted hazard ratio (HR) 1.26 (per 100 joule increase), p < 0.01] and tended to be associated with cardiac death (adjusted HR 1.30, p = 0.08). The survival rate of patients with high shock energy accumulation (≥182 joule) was lower (p < 0.05), as compared to low shock energy accumulation (<182 joule), likewise to no shock. Besides, the relation between high shock energy accumulation and all-cause death was remarkable in the patients with low left ventricular ejection fraction (LVEF ≤40%) or atrial fibrillation (AF). CONCLUSIONS: Increase of shock energy was related to mortality in ICD recipients. This relation was evident in patients with low LVEF or AF.

Ratio of pro-B-type natriuretic peptide (BNP) to total BNP is decreased in mild, but not severe, acute decompensated heart failure patients: A novel compensatory mechanism for acute heart failure.
Hiroyuki Takahama, Seiji Takashio, Toshio Nishikimi, Tomohiro Hayashi, Chiaki Nagai-Okatani, Yasuaki Nakagawa, Makoto Amaki, Takahiro Ohara, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Satoshi Yasuda, Kenji Kangawa, Naoto Minamino, Toshihisa Anzai
International journal of cardiology, 258, 165, 171, 01 May 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: A recent study showed that both glycosylation of pro-B-type natriuretic peptide (BNP) and the proBNP/total BNP ratio are decreased in acute decompensated heart failure (ADHF). However, the following points regarding the proBNP/total BNP ratio have not been determined in patients with ADHF: 1) the relationship with the severity of ADHF, 2) the changes in the ratio during treatment, and 3) the relationship with cyclic guanosine monophosphate (cGMP)-generating activity. METHODS: Plasma proBNP and total BNP (proBNP+mature BNP) were measured in patients with ADHF (n=154). Measurement was performed on admission, 3 and 7days after admission, and before discharge using recently developed sandwich chemiluminescence enzyme immunoassays. The percent proBNP was calculated as: (proBNP/total BNP)×100. RESULTS: On admission, %proBNP was higher in patients with severe ADHF than in patients with mild ADHF (median: 61.7% vs. 56.2%, respectively; p<0.01), while the plasma cGMP/total BNP ratio, an index of the biological activity of BNP, was lower (p<0.001). In patients with severe ADHF, the higher %proBNP and lower cGMP/total BNP ratio were unchanged during hospitalization, whereas %proBNP increased gradually in patients with mild ADHF and the cGMP/total BNP ratio also increased at 3days after admission. CONCLUSION: These findings suggest that in patients with mild ADHF, compensation for heart failure occurs via increased proBNP processing, leading to increase of mature BNP and activation of the BNP/cGMP cascade. In contrast, this compensatory mechanism may be impaired in patients with severe ADHF and a vicious cycle can potentially occur.

Successful Treatment of Mitral Regurgitation after Transapical Transcatheter Aortic Valve Implantation by Percutaneous Edge-to-edge Mitral Valve Repair (MitraClip®) -The First Combination Therapy Performed in Japan.
Atsushi Okada, Hideaki Kanzaki, Makoto Amaki, Yu Kataoka, Koji Miyamoto, Yasuhiro Hamatani, Masashi Fujino, Hiroyuki Takahama, Takuya Hasegawa, Yusuke Shimahara, Yoshiaki Morita, Yasuo Sugano, Kengo Kusano, Yoshihiko Ohnishi, Tomoyuki Fujita, Junjiro Kobayashi, Toshihisa Anzai, Satoshi Yasuda
Internal medicine (Tokyo, Japan), 57, 8, 1105, 1109, 15 Apr. 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, A 75-year old man with a history of inferior myocardial infarction was admitted with symptoms of progressive heart failure 3 months after undergoing transapical transcatheter aortic valve implantation (TAVI). Echocardiography revealed severe mitral regurgitation (MR) caused by posterior leaflet tethering, without traumatic injury of the mitral valve or chordae. The patient was successfully treated by percutaneous edge-to-edge mitral valve repair (MitraClip®). This case highlights the role of MitraClip® in high-risk patients suffering from MR, and suggests that apical contractile loss or adhesion caused by apical puncture and suturing in transapical TAVI may be one of the mechanisms of worsening MR.

Assessment of renal perfusion impairment in a rat model of acute renal congestion using contrast-enhanced ultrasonography
Kaoru Komuro, Yoshihiro Seo, Masayoshi Yamamoto, Seika Sai, Tomoko Ishizu, Kyo Shimazu, Yumi Takahashi, Shogo Imagawa, Teisuke Anzai, Kazuya Yonezawa, Kazutaka Aonuma
Heart and Vessels, 33, 4, 434, 440, Springer Tokyo, 01 Apr. 2018, [Peer-reviewed]
English, Scientific journal

Increased serum Wisteria floribunda agglutinin positive Mac-2 binding protein (Mac-2 binding protein glycosylation isomer) in chronic heart failure: a pilot study.
Atsushi Okada, Hideaki Kanzaki, Yasuhiro Hamatani, Seiji Takashio, Hiroyuki Takahama, Makoto Amaki, Takuya Hasegawa, Yasuo Sugano, Satoshi Yasuda, Toshihisa Anzai
Heart and vessels, 33, 4, 385, 392, Apr. 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: Serum Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA+-M2BP) or Mac-2 Binding Protein Glycosylation Isomer (M2BPGi) is a novel biomarker currently applied for evaluating hepatic fibrosis. The aim of this study was to evaluate the utility of serum WFA+-M2BP level as a biomarker in chronic heart failure (HF) patients with abnormal liver function. METHODS AND RESULTS: Fifty chronic HF patients who underwent measurement of serum WFA+-M2BP were evaluated. The median value of serum WFA+-M2BP was 0.88 (interquartile range 0.48-1.29) cut-off index, and positive WFA+-M2BP (≥ 1.00 cut-off index) was observed in 22 (44%). Elevated WFA + -M2BP was associated with longer HF history, older age, female sex, valvular heart disease, decreased estimated glomerular filtration rate (eGFR), albumin, and cholinesterase. Stepwise multiple regression analysis showed that HF history, eGFR, and albumin were independent determinants of serum WFA+-M2BP values. Repeated measurements of serum WFA+-M2BP suggested association between the decrease of WFA+-M2BP and improvement of New York Heart Association (NYHA) functional class. CONCLUSIONS: Elevation of serum WFA+-M2BP showed a high prevalence in chronic HF patients with abnormal liver function with relation to HF history, decreased hepatic protein synthesis, and renal dysfunction. Our results suggest that serum WFA+-M2BP may be a novel biomarker of chronic HF.

Response to letter regarding article by Formiga et al., "Utility of the Controlling Nutritional Status (CONUT) score in patients admitted due to acute heart failure".
Naotsugu Iwakami, Toshiyuki Nagai, Toshiaki A Furukawa, Toshihisa Anzai
International journal of cardiology, 256, 25, 25, 01 Apr. 2018, [Peer-reviewed], [International Magazine]
English

An Exploratory Study of Dapagliflozin for the Attenuation of Albuminuria in Patients with Heart Failure and Type 2 Diabetes Mellitus (DAPPER).
Fumiki Yoshihara, Miki Imazu, Toshimitsu Hamasaki, Toshihisa Anzai, Satoshi Yasuda, Shin Ito, Haruko Yamamoto, Kazuhiko Hashimura, Yoshio Yasumura, Kiyoshi Mori, Masataka Watanabe, Masanori Asakura, Masafumi Kitakaze
Cardiovascular drugs and therapy, 32, 2, 183, 190, Apr. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND AND AIMS: Sodium-dependent glucose transporter-2 (SGLT-2) inhibitors, which are anti-diabetic drugs, reportedly decrease the incidence of cardiovascular events in high-risk patients with cardiovascular diseases, and thus chronic heart failure (CHF). SGLT-2 inhibitors also decrease albuminuria in patients with type 2 diabetes mellitus (T2D). Since albuminuria is a biomarker of not only chronic kidney disease but also cardiovascular events, we hypothesized that, among T2D patients with CHF, SGLT-2 inhibitors will decrease the extent of albuminuria and also improve CHF concomitantly. METHODS: DAPPER (UMIN000025102) is a multicenter, randomized, open-labeled, parallel-group, standard treatment-controlled study, which is designed to evaluate whether dapagliflozin, one of the SGLT-2 inhibitors, decreases albuminuria in T2D patients with CHF and exerts cardioprotective effects on the failing heart. The patients are randomized to either of the dapagliflozin (5 or 10 mg, once daily orally) or control group (administration of anti-diabetic drugs administered other than SGLT 2 inhibitors). The estimated number of patients that need to be enrolled is 446 in total (223 in each group). The primary objective is the changes in the urinary albumin-to-creatinine ratio from the baseline after 2-year treatment. The key secondary objectives are (1) the safety of dapagliflozin and (2) the cardiovascular and renal efficacies of dapagliflozin. CONCLUSION AND PERSPECTIVES: DAPPER study investigates whether dapagliflozin decreases albuminuria and exerts beneficial effects on the failing heart in T2D patients. (UMIN000025102).

Mortality and Sudden Cardiac Death Risk Stratification Using the Noninvasive Combination of Wide QRS Duration and Late Gadolinium Enhancement in Idiopathic Dilated Cardiomyopathy.
Kyohei Marume, Teruo Noguchi, Emi Tateishi, Yoshiaki Morita, Tsukasa Kamakura, Kohei Ishibashi, Takashi Noda, Hiroyuki Miura, Kunihiro Nishimura, Michikazu Nakai, Naoaki Yamada, Kenichi Tsujita, Toshihisa Anzai, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda
Circulation. Arrhythmia and electrophysiology, 11, 4, e006233, Apr. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: The aim of this study was to investigate whether the combination of QRS duration ≥120 ms (wide QRS duration [wQRS]) and late gadolinium enhancement (LGE) is a precise prognostic indicator for dilated cardiomyopathy. METHODS AND RESULTS: We investigated the association between the combination of LGE plus wQRS and the primary end point (all-cause death) and a composite of sudden cardiac death (SCD) or aborted SCD in 531 patients with dilated cardiomyopathy. We also analyzed the association between the combination of LGE and wQRS and these end points among patients with a class I indication for implantable cardioverter defibrillator implantation. We divided study patients into 3 groups according to LGE status and QRS duration: 2 negative indices (LGE negative and narrow QRS), 1 positive index (LGE positive or wQRS), or 2 positive indices (LGE positive and wQRS), and followed them for 3.8 years. Multivariable Cox regression analysis identified 2 positive indices as a significant predictor of all-cause death (hazard ratio, 4.29 [1.19-15.47]; P=0.026). Among 317 patients with a class I indication for implantable cardioverter defibrillator, the 5-year event rate of SCD or aborted SCD was the lowest in the 2 negative indices group (1.4%). With propensity score-matching cohorts, the 2 negative indices group had a significantly lower event rate of SCD or aborted SCD than the other 2 groups (hazard ratio, 0.12 [0.01-0.97]; P=0.046). CONCLUSIONS: The combination of LGE and wQRS provides additional prognostic stratification compared with LGE status alone and might improve the appropriate use of implantable cardioverter defibrillator therapy in patients with dilated cardiomyopathy.

Long-Term Prognostic Significance of Plasma B-Type Natriuretic Peptide Level in Patients With Acute Heart Failure With Reduced, Mid-Range, and Preserved Ejection Fractions.
Yasuhiro Hamatani, Toshiyuki Nagai, Yasuyuki Shiraishi, Shun Kohsaka, Michikazu Nakai, Kunihiro Nishimura, Takashi Kohno, Yuji Nagatomo, Yasuhide Asaumi, Ayumi Goda, Atsushi Mizuno, Satoshi Yasuda, Hisao Ogawa, Tsutomu Yoshikawa, Toshihisa Anzai
The American journal of cardiology, 121, 6, 731, 738, 15 Mar. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Plasma B-type natriuretic peptide (BNP) is an important prognostic marker in patients with acute heart failure (AHF). However, it is unclear which BNP parameter, on admission, at discharge, or change during hospitalization, has the highest predictive performance for long-term adverse outcomes, and whether its prognostic impact differs according to the new European heart failure (HF) phenotype classification by left ventricular ejection fraction: heart failure with reduced ejection fraction (HFrEF), heart failure with mid-range ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). We examined 1,792 patients with AHF consisting of 860 (48%) HFrEFs, 318 (18%) HFmrEFs, and 614 (34%) HFpEFs. Prognostic performance of each BNP parameter was assessed by the Harrell c-index. During a median follow-up of 664 days, 344 (19%) patients died. Discharge BNP had the highest c-index (0.69) for mortality among all BNP parameters (p <0.001). In multivariate Cox proportional hazard modeling, discharge BNP was associated with mortality in HFrEF, HFmrEF, and HFpEF patients with significant interaction (hazard ratio [HR] 1.95, 95% confidence interval [CI] 1.57 to 2.41; HR 1.76, 95% CI 1.10 to 2.82; HR 1.46, 95% CI 1.12 to 1.91, respectively; p = 0.011 for interaction). Moreover, the c-index of discharge BNP for mortality in HFrEF patients (0.72) was higher than that in HFmrEF patients (0.68) and HFpEF patients (0.65). Similar results were obtained for mortality or HF rehospitalization as alternative outcomes, except there was no statistically significant interaction among HF phenotypes. In conclusion, discharge BNP is a more reliable marker than other BNP parameters on long-term outcome prediction in patients with AHF, but its prognostic impact may be weakened in HFmrEF and HFpEF compared with HFrEF.

閉塞性肥大型心筋症における僧帽弁apparatusを評価するための3D印刷の新たな役割(Emerging Role of the Three-dimensional Printing for the Assessment of Mitral Apparatus in Hypertrophic Obstructive Cardiomyopathy)　　　　　　　　　　　　　　　
Hamatani Yasuhiro, Amaki Makoto, Kanzaki Hideaki, Nakai Eri, Kato Yuta, Kadota Muneyuki, Hitsumoto Tatsuro, Ito Nobuyasu, Okada Atsushi, Takahama Hiroyuki, Hasegawa Takuya, Shimahara Yusuke, Sugano Yasuo, Fujita Tomoyuki, Shiraishi Isao, Yasuda Satoshi, Kobayashi Junjiro, Anzai Toshihisa
日本循環器学会学術集会抄録集, 82回, PL3, 4, (一社)日本循環器学会, Mar. 2018
English

拡張型心筋症患者におけるC反応性蛋白/アルブミン比と心不全重症度および予後との関連(Association of C-reactive Protein/Albumin Ratio with Heart Failure Severity and Prognosis in Patients with Dilated Cardiomyopathy)　　　　　　　　　　　　　　　
Terasaki Satoshi, Sugano Yasuo, Kadota Muneyuki, Okada Atsushi, Hamatani Yasuhiro, Takahama Hiroyuki, Amaki Makoto, Hasegawa Takuya, Kanzaki Hideaki, Yasuda Satoshi, Anzai Toshihisa
日本循環器学会学術集会抄録集, 82回, OE08, 3, (一社)日本循環器学会, Mar. 2018
English

慢性心不全における肝線維化に関する血清マーカーの可能性(Potential of Serum Markers of Hepatic Fibrosis in Chronic Heart Failure)　　　　　　　　　　　　　　　
Okada Atsushi, Kanzaki Hideaki, Hamatani Yasuhiro, Takahama Hiroyuki, Amaki Makoto, Hasegawa Takuya, Sugano Yasuo, Yasuda Satoshi, Anzai Toshihisa
日本循環器学会学術集会抄録集, 82回, OE09, 4, (一社)日本循環器学会, Mar. 2018
English

肥大型心筋症における心室性不整脈の予測 ESCリスク予測モデルの検証と拡張相肥大型心筋症における役割(Prediction of Ventricular Arrhythmia in Hypertrophic Cardiomyopathy: Validation of ESC Risk Prediction Model and Role in Dilated Phase Hypertrophic Cardiomyopathy)　　　　　　　　　　　　　　　
Nakagawa Shoko, Okada Atsushi, Hamatani Yasuhiro, Takahama Hiroyuki, Amaki Makoto, Hasegawa Takuya, Sugano Yasuo, Kanzaki Hideaki, Kusano Kengo, Yasuda Satoshi, Anzai Toshihisa
日本循環器学会学術集会抄録集, 82回, OE31, 8, (一社)日本循環器学会, Mar. 2018
English

非虚血性拡張型心筋症患者においてtenascin-Cの心筋発現は駆出率の回復を阻害する(Myocardial Tenascin-C Expression Inhibits Recovery of Ejection Fraction in Patients with Non-Ischemic Dilated Cardiomyopathy)　　　　　　　　　　　　　　　
Sugano Yasuo, Kadota Muneyuki, Ohgoh Keiko, Hamatani Yasuhiro, Okada Atsushi, Takahama Hiroyuki, Amaki Makoto, Hasegawa Takuya, Kanzaki Hideaki, Ikeda Yoshihiko, Ishibashi-Ueda Hatsue, Yasuda Satoshi, Anzai Toshihisa
日本循環器学会学術集会抄録集, 82回, OE32, 7, (一社)日本循環器学会, Mar. 2018
English

拡張型心筋症患者の心臓MRIにおける心筋native T1値は左室逆リモデリングを効果的に予測する(Myocardial Native T1 Time in Cardiac MRI Effectively Predicts Left Ventricular Reverse Remodeling in Patients with Dilated Cardiomyopathy)　　　　　　　　　　　　　　　
Kadota Muneyuki, Sugano Yasuo, Miura Hiroyuki, Noguchi Teruo, Morita Yoshiaki, Hamatani Yasuhiro, Okada Atsushi, Takahama Hiroyuki, Amaki Makoto, Hasegawa Takuya, Kanzaki Hideaki, Yasuda Satoshi, Anzai Toshihisa
日本循環器学会学術集会抄録集, 82回, OE67, 1, (一社)日本循環器学会, Mar. 2018
English

無症候性器質的僧帽弁逆流における最大僧帽弁流入血流速度が予後にもたらす影響(Prognostic Impact of Peak Mitral Inflow Velocity in Asymptomatic Degenerative Mitral Regurgitation)　　　　　　　　　　　　　　　
Okamoto Chisato, Okada Atsushi, Kanzaki Hideaki, Hamatani Yasuhiro, Takahama Hiroyuki, Amaki Makoto, Hasegawa Takuya, Sugano Yasuo, Fujita Tomoyuki, Kobayashi Junjiro, Yasuda Satoshi, Anzai Toshihisa
日本循環器学会学術集会抄録集, 82回, OE79, 1, (一社)日本循環器学会, Mar. 2018
English

加齢に伴う左室機能の変化における性差(Gender Differences in the Change in Left Ventricular Function with Aging)　　　　　　　　　　　　　　　
Hasegawa Takuya, Asakura Masanori, Sakamoto Mari, Hamatani Yasuhiro, Okada Atsushi, Amaki Makoto, Takahama Hiroyuki, Sugano Yasuo, Kanzaki Hideaki, Yasuda Satoshi, Anzai Toshihisa, Kitakaze Masafumi
日本循環器学会学術集会抄録集, 82回, PE002, 2, (一社)日本循環器学会, Mar. 2018
English

卵円孔開存シャント流の方向の臨床的意義(Clinical Implication of the Direction of the Shunt Flow of Patent Foramen Ovale)　　　　　　　　　　　　　　　
Hitsumoto Tatsuro, Hasegawa Takuya, Hamatani Yasuhiro, Okada Atsushi, Takahama Hiroyuki, Amaki Makoto, Sugano Yasuo, Kanzaki Hideaki, Yasuda Satoshi, Anzai Toshihisa
日本循環器学会学術集会抄録集, 82回, PE055, 4, (一社)日本循環器学会, Mar. 2018
English

経皮的僧帽弁修復1年追跡後の機能的僧帽弁逆流における心拍出量改善に関する血行動態的決定因子(Hemodynamic Determinant of Improved Cardiac Output in Functional Mitral Regurgitation after One Year Followup of Percutaneous Mitral Valve Repair)　　　　　　　　　　　　　　　
Amaki Makoto, Kataoka Yu, Kanzaki Hideaki, Miyamoto Koji, Hasegawa Takuya, Hamatani Yasuhiro, Okada Atsushi, Fujino Masashi, Takahama Hiroyuki, Sugano Yasuo, Kusano Kengo, Ohnishi Yoshihiko, Fujita Tomoyuki, Kobayashi Junjiro, Anzai Toshihisa, Yasuda Satoshi
日本循環器学会学術集会抄録集, 82回, PE074, 2, (一社)日本循環器学会, Mar. 2018
English

MitraClipを用いた経皮的edge-to-edge僧帽弁修復の長期血行動態的効果 日本での初期経験からの知見(Long-term Hemodynamic Effects of Percutaneous Edge-to-edge Mitral Valve Repair Using MitraClip: Insights from Initial Japanese Experience)　　　　　　　　　　　　　　　
Okada Atsushi, Kanzaki Hideaki, Amaki Makoto, Kataoka Yu, Miyamoto Koji, Hamatani Yasuhiro, Fujino Masashi, Takahama Hiroyuki, Hasegawa Takuya, Sugano Yasuo, Kusano Kengo, Ohnishi Yoshihiko, Fujita Tomoyuki, Kobayashi Junjiro, Anzai Toshihisa, Yasuda Satoshi
日本循環器学会学術集会抄録集, 82回, PE128, 3, (一社)日本循環器学会, Mar. 2018
English

左室駆出率(LVEF)の低下を伴う患者における経カテーテル大動脈弁留置術後のLVEF改善に関する血行動態的決定因子(Hemodynamic Determinant of Improvement in Left Ventricular Ejection Fraction(LVEF) after Transcatheter Aortic Valve Implantation in Patients with Reduced LVEF)　　　　　　　　　　　　　　　
Ito Nobuyasu, Amaki Makoto, Kanzaki Hideaki, Okada Atsushi, Hamatani Yasuhiro, Takahama Hiroyuki, Hasegawa Takuya, Sugano Yasuo, Yamashita Kizuku, Kume Yuta, Shimahara Yusuke, Fujita Tomoyuki, Yasuda Satoshi, Anzai Toshihisa, Kobayashi Junjiro
日本循環器学会学術集会抄録集, 82回, PE128, 6, (一社)日本循環器学会, Mar. 2018
English

心不全患者の予後不良予測因子としての呼気中acetone濃度の初期変化(Initial Change in Exhaled Acetone Concentration as a Predictive Factor for Poor Outcome in Heart Failure Patients)　　　　　　　　　　　　　　　
Ito Nobuyasu, Sugano Yasuo, Okumura Naoya, Hamatani Yasuhiro, Okada Atsushi, Takahama Hiroyuki, Amaki Makoto, Hasegawa Takuya, Kanzaki Hideaki, Yasuda Satoshi, Anzai Toshihisa
日本循環器学会学術集会抄録集, 82回, PE134, 1, (一社)日本循環器学会, Mar. 2018
English

呼気中低分子量化合物は心不全の新規非侵襲的バイオマーカーになり得る(Low-molecular Weight Compounds in the Breath as Potential Novel Noninvasive Biomarkers for Heart Failure)　　　　　　　　　　　　　　　
Ito Nobuyasu, Sugano Yasuo, Okumura Naoya, Hamatani Yasuhiro, Okada Atsushi, Takahama Hiroyuki, Amaki Makoto, Hasegawa Takuya, Kanzaki Hideaki, Yasuda Satoshi, Anzai Toshihisa
日本循環器学会学術集会抄録集, 82回, PE157, 2, (一社)日本循環器学会, Mar. 2018
English

LONG-TERM EFFECTS OF ANGIOTENSIN CONVERTING ENZYME INHIBITOR ON LEFT VENTRICULAR EJECTION FRACTION IN DUCHENNE AND BECKER MUSCULAR DYSTROPHY: A LONGITUDINAL CARDIAC MAGNETIC RESONANCE IMAGING STUDY
Tadao Aikawa, Atsuhito Takeda, Noriko Oyama-Manabe, Masanao Naya, Hirokuni Yamazawa, Kazuhiro Koyanagawa, Yoichi M. Ito, Yuka Ishikawa, Yukitoshi Ishikawa, Toshihisa Anzai
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 71, 11, 1565, 1565, Mar. 2018, [Peer-reviewed]
English

Long-term prognostic significance of urinary sodium concentration in patients with acute heart failure.
Satoshi Honda, Toshiyuki Nagai, Kunihiro Nishimura, Michikazu Nakai, Yasuyuki Honda, Hiroki Nakano, Naotsugu Iwakami, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hiroyuki Yokoyama, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
International journal of cardiology, 254, 189, 194, 01 Mar. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Lower urinary sodium concentration (UNa) may reflect impaired renal perfusion, higher neurohormonal activity and diuretic resistance. However, the prognostic impact of UNa in patients with acute heart failure (AHF) has not been fully elucidated. METHODS: We investigate the association between UNa and clinical outcomes in 669 patients admitted with AHF in our prospective registry. Patients were stratified into tertiles based on UNa in a spot urine sample on admission. RESULTS: Patients with lower UNa were more likely to have a history of prior heart failure admission, β-blockers and diuretics use, and had lower blood pressure and serum sodium level, and higher blood urea nitrogen, estimated glomerular filtration rate, blood glucose and troponin T levels on admission than those with higher UNa. Plasma renin activity, aldosterone, cortisol and dopamine levels were also significantly higher in patients with lower UNa (all p<0.001). Furthermore, patients with lower UNa had significantly less weight loss, lower net fluid loss/furosemide equivalent dose and higher incidence of worsening renal function during hospitalization than those with higher UNa (all p<0.01). During a median follow-up period of 560days, lower UNa was significantly associated with the composite of all-cause death and worsening heart failure (p<0.001). In multivariable Cox-proportional hazards model, UNa remained an independent determinant of long-term adverse events (HR, 1.24, 95% CI, 1.06-1.45, p=0.006). CONCLUSIONS: Lower UNa was associated with worse long-term clinical outcomes along with increased neurohormonal activities, impaired response to diuretics and higher incidence of worsening renal function in patients with AHF.

Inflammatory Mechanisms of Cardiovascular Remodeling.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 82, 3, 629, 635, 23 Feb. 2018, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Inflammation and fibrosis play an important role in the development and progression of cardiovascular diseases. Acute coronary syndrome (ACS) is caused by rupture of inflamed atherosclerotic plaque and subsequent atherothrombosis. Recent studies have shown that inflammatory markers such as C-reactive protein (CRP) can predict ACS development and have demonstrated the effectiveness of new therapeutic approaches targeting inflammation. Studies have also shown that an enhanced inflammatory response after myocardial infarction (MI) is associated with cardiac rupture, ventricular aneurysm formation, and exacerbation of left ventricular (LV) remodeling. Inflammation is a physiological reaction in which fibrosis is induced to facilitate the healing of tissue damage. However, when an excessive inflammatory response consisting mainly of monocytes/macrophages is induced by various factors, impaired reparative fibrosis and resulting pathological remodeling processes may occur. A similar phenomenon is observed in abdominal aortic aneurysm (AAA) expansion. In contrast, myocardial diseases such as inflammatory dilated cardiomyopathy (DCMI) and valvular diseases such as aortic valve stenosis (AS) are characterized by chronic inflammation mediated mainly by T lymphocytes and the associated enhancement of reactive fibrosis. Thus, inflammation can take 2 paths (the inhibition or promotion of fibrosis), depending on the phase of inflammation, inducing pathological cardiovascular remodeling. Elucidation of the regulatory mechanisms of inflammation and fibrosis will contribute to the development of new therapeutic approaches for cardiovascular diseases.

Diagnostic utility of cardiac troponin T level in patients with cardiac amyloidosis.
Seiji Takashio, Megumi Yamamuro, Yasuhiro Izumiya, Kyoko Hirakawa, Kyohei Marume, Masahiro Yamamoto, Mitsuharu Ueda, Taro Yamashita, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Hisao Ogawa, Yukio Ando, Toshihisa Anzai, Kenichi Tsujita
ESC heart failure, 5, 1, 27, 35, Feb. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIM: The aim of this study was to evaluate the diagnostic utility of high-sensitivity cardiac troponin T (hs-cTnT) levels in discriminating cardiac amyloidosis from patients with cardiac hypertrophy caused by aetiologies other than cardiac amyloidosis. METHODS AND RESULTS: Serum hs-cTnT levels were measured in 96 patients with cardiac amyloidosis (light chain: 23, wild-type transthyretin amyloidosis: 40, and mutated transthyretin amyloidosis: 33), and 91 patients with other causes of cardiac hypertrophy who were confirmed to have no cardiac amyloidosis by endomyocardial biopsy (control group). The diagnostic utility and cut-off value of hs-cTnT were evaluated by receiver operating characteristic analysis. The median hs-cTnT levels were higher in cardiac amyloidosis than the control group [0.048 (0.029-0.073) vs. 0.016 (0.010-0.031) ng/mL; P < 0.001]. High levels of hs-cTnT were suggestive of cardiac amyloidosis (cut-off value: 0.0312 ng/mL, sensitivity: 0.74, specificity: 0.76, area under the curve: 0.788; 95% confidence interval: 0.723-0.854, P < 0.001), compared with brain natriuretic peptide and E/e' ratio. The hs-cTnT levels were also useful in differentiating each type of amyloidosis from the control group. Multivariate analysis identified log hs-cTnT as an independent diagnostic factor for cardiac amyloidosis (odds ratio: 2.22; 95% confidence interval: 1.30-3.80; P = 0.004). CONCLUSIONS: High serum levels of hs-cTnT are highly suggestive of cardiac amyloidosis, allowing its differentiation from cardiac hypertrophy of other aetiologies. Further refined diagnostic approaches that include imaging modalities and histopathological examination are needed for these patients to avoid underdiagnosis of cardiac amyloidosis.

Anticoagulation combined with antiplatelet therapy in patients with left ventricular thrombus after first acute myocardial infarction.
Naoki Maniwa, Masashi Fujino, Michikazu Nakai, Kunihiro Nishimura, Yoshihiro Miyamoto, Yu Kataoka, Yasuhide Asaumi, Yoshio Tahara, Michio Nakanishi, Toshihisa Anzai, Kengo Kusano, Takashi Akasaka, Yoichi Goto, Teruo Noguchi, Satoshi Yasuda
European heart journal, 39, 3, 201, 208, 14 Jan. 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Aims: There are limited data about the optimal anti-thrombotic therapy for preventing embolism while minimizing bleeding events in patients with first acute myocardial infarction (AMI) complicated by left ventricular thrombus (LVT). Methods and results: Among 2301 consecutive patients with AMI hospitalized between 2001 and 2014, we studied 1850 patients with first AMI who discharged alive to investigate clinical characteristics, incidence of systemic embolism (SE), and association between anticoagulation and embolic or bleeding events. Left ventricular thrombus was diagnosed by echocardiography, left ventriculography, or cardiac magnetic resonance imaging in 92 (5.0%) patients (62 ± 12 years). During a median follow-up period of 5.4 years (interquartile range 2.1-9.1 years), SE occurred in 15 of 92 patients with LVT (16.3%) and 51 of 1758 patients without LVT (2.9%), respectively. Kaplan-Meier analysis showed a significantly higher incidence of SE in the LVT group (log-rank test, P < 0.001). Multivariate analysis showed that LVT was an independent predictor of SE. Among the LVT patients treated with vitamin K antagonists (n = 84), we compared the patients with therapeutic range (TTR) ≥50% (n = 34) and those with TTR <50% (n = 50). Only one embolic event developed in the TTR ≥50% group and nine embolic events developed in the TTR <50% group (2.9% vs. 19%, P = 0.036). There was no difference in major bleeding events (TTR ≥50%; 9% vs. TTR <50%; 8%, P = 0.89). Conclusion: Appropriate anticoagulation therapy may decrease the incidence of embolic events without increasing the incidence of bleeding events in patients with first AMI complicated by LV thrombus.

Mortality after admission for heart failure in the UK compared with Japan.
Toshiyuki Nagai, Varun Sundaram, Kieran Rothnie, Jennifer Kathleen Quint, Ahmad Shoaib, Yasuyuki Shiraishi, Shun Kohsaka, Susan Piper, Theresa A McDonagh, Suzanna Marie C Hardman, Ayumi Goda, Atsushi Mizuno, Takashi Kohno, Alan S Rigby, Tsutomu Yoshikawa, Andrew L Clark, Toshihisa Anzai, John G F Cleland
Open heart, 5, 2, e000811, 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Objective: Mortality amongst patients hospitalised for heart failure (HHF) in Western and Asian countries may differ, but this has not been investigated using individual patient-level data (IPLD). We sought to remedy this through rigorous statistical analysis of HHF registries and variable selection from a systematic literature review. Methods and results: IPLD from registries of HHF in Japan (n=3781) and the UK (n=894) were obtained. A systematic literature review identified 23 models for predicting outcome of HHF. Five variables appearing in 10 or more reports were strongly related to prognosis (systolic blood pressure, serum sodium concentration, age, blood urea nitrogen and creatinine). To compare mortality in the UK and Japan, variables were imputed in a propensity model using inverse probability of treatment weighting (IPTW) and IPTW with logistic regression (doubly robust IPTW). Overall, patients in the UK were sicker and in-patient and post-discharge mortalities were greater, suggesting that the threshold for hospital admission was higher. Covariate-adjusted in-hospital mortality was similar in the UK and Japan (IPTW OR: 1.14, 95% CI 0.70 to 1.86), but 180-day postdischarge mortality was substantially higher in the UK (doubly robust IPTW OR: 2.33, 95% CI 1.58 to 3.43). Conclusions: Despite robust methods to adjust for differences in patient characteristics and disease severity, HHF patients in the UK have roughly twice the mortality at 180 days compared with those in Japan. Similar analyses should be done using other data sets and in other countries to determine the consistency of these findings and identify factors that might inform healthcare policy and improve outcomes.

Decrease in exhaled hydrogen as marker of congestive heart failure.
Atsushi Shibata, Yasuo Sugano, Akito Shimouchi, Tetsuro Yokokawa, Naoya Jinno, Hideaki Kanzaki, Keiko Ohta-Ogo, Yoshihiko Ikeda, Hideshi Okada, Takeshi Aiba, Kengo Kusano, Mikiyasu Shirai, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
Open heart, 5, 2, e000814, 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, Objective: Hydrogen excretion is thought to be related to systemic antioxidation activity. H2 selectively reduces the hydroxyl radical of free hydrogen (·OH), a highly cytotoxic form of reactive oxygen species, in cultured cells. Methods: We investigated whether exhaled H2 decreased during night sleep, reflected ·OH production and was associated with heart failure severity. We enrolled 108 patients with chronic heart failure (CHF) and 15 control participants without CHF. H2 concentration was measured by gas chromatography in exhaled breath collected before sleep and in the morning after overnight fasting. Overnight change in H2 concentration (ΔH2) was calculated. Mitochondrial morphology evaluated by transmission electron microscopy in endomyocardial biopsies collected from 18 patients with dilated cardiomyopathy. Results: ΔH2 was significantly lower in patients with CHF compared with controls (-4.3±1.0 vs 2.0±2.1 ppm, p=0.030) and was positively correlated with cardiac index (CI; r = -0.285, p=0.003). Patients with a ΔH2<0 ppm had a significantly lower CI compared with those who had a ΔH2>0 ppm (2.85±0.61 vs 3.24±0.65 L/min/m2, p=0.005). ΔH2 was negatively correlated with both the percentage of vacuole-containing mitochondria and indices of cristae remodelling (r = -0.61, p=0.007). Conclusions: Decrease in exhaled H2 during night sleep was associated with CHF severity. ΔH2 warrants investigation as marker of CHF severity.

Presence of increased inflammatory infiltrates accompanied by activated dendritic cells in the left atrium in rheumatic heart disease.
Mikio Shiba, Yasuo Sugano, Yoshihiko Ikeda, Hideshi Okada, Toshiyuki Nagai, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
PloS one, 13, 9, e0203756, 2018, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIMS: Left atrial (LA) structural remodelling develops in rheumatic heart disease (RHD) according to the disease severity of the mitral valve and the presence of atrial fibrillation. Sustained active inflammation has been previously reported in the LA of patients with RHD, suggesting a direct role of cell-mediated immunity in the pathogenesis of LA remodelling. Dendritic cells (DCs) have a major antigen-presenting role, and are known as crucial modulators of innate and adaptive immunity. We investigated whether DCs are involved in the pathogenesis of LA remodelling in RHD. METHODS AND RESULTS: Immunohistochemical analyses were performed using antibodies to CD11c, CD209 and CD80 as markers of myeloid DCs, migratory-active DCs, mature DCs and infiltrated inflammatory cells including T lymphocytes (CD3) and M1 (CD68; pro-inflammatory profile) and M2 (CD163; pro-resolution profile) macrophages. Furthermore, tenascin-C, an extracellular matrix (ECM) protein that appears during ECM remodelling and inflammatory response, was examined. Infiltrated myeloid DCs, migratory-active DCs, mature DCs and other inflammatory infiltrates including T lymphocytes and M1 and M2 macrophages, were significantly higher in the RHD group than the non-RHD group. The positive area fraction for tenascin-C was significantly higher in the RHD group than in the non-RHD group. CONCLUSION: Our histological findings suggest that inflammation may persist long after a bout of rheumatic fever, ultimately leading to ECM remodelling. We identified and quantitatively assessed several subsets of DCs and other immunocompetent cells, and our results indicated that activation of DCs has some role in persistence of LA inflammation in patients with chronic RHD.

Effect of Mitral Valve Surgery in Patients With Dilated Cardiomyopathy and Severe Functional Mitral Regurgitation.
Hyemoon Chung, Makoto Amaki, Seiji Takashio, Hiroyuki Takahama, Takahiro Ohara, Takuya Hasegawa, Yasuo Sugano, Tomoyuki Fujita, Junjiro Kobayashi, Masanori Asakura, Hideaki Kanzaki, Toshihisa Anzai, Masafumi Kitakaze
Circulation journal : official journal of the Japanese Circulation Society, 82, 1, 131, 140, 25 Dec. 2017, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: Surgical treatment of functional mitral regurgitation (FMR) improves ventricular remodeling in patients with dilated cardiomyopathy (DCM). However, it is unclear whether surgical treatment improves long-term outcomes. We investigated the effects of mitral valve (MV) surgery in patients with DCM and FMR.Methods and Results:Of 525 patients with DCM hospitalized due to heart failure between January 1996 and September 2014, 70 who had severe FMR despite receiving optimal medical therapy were enrolled in the study. Of these patients, 16 underwent surgery for FMR (surgery group; repair=14, replacement=2); the remaining 54 who refused or decided not to undergo surgery were classified as the medication group. There were no differences in age, sex, medication, or echocardiographic parameters between the 2 groups (P>0.05). During the mean follow-up period of 53.6±43.6 months, the occurrence of clinical outcomes (i.e., all-cause death or left ventricular assist device implantation) was 54.3%; the occurrence of clinical outcomes was lower in the surgery group (P=0.008, log-rank test). Multivariate Cox regression analysis using clinical data revealed that MV surgery (hazard ratio [HR] 0.257, 95% confidence interval [CI] 0.103-0.640; P=0.004) and diabetes mellitus (HR 2.924, 95% CI 1.243-6.876; P=0.014) were independent predictors of clinical outcomes after adjusting for age and sex. CONCLUSIONS: Surgery for severe FMR provides better long-term outcomes in patients with DCM.

Transcatheter Aortic Valve Implantation for Degenerated 19-mm Aortic Bioprosthetic Valve.
Kizuku Yamashita, Tomoyuki Fujita, Satsuki Fukushima, Yusuke Shimahara, Yuta Kume, Yorihiko Matsumoto, Naonori Kawamoto, Tatsuro Hitsumoto, Nobuyasu Ito, Yasuhiro Hamatani, Atsushi Okada, Hiroyuki Takahama, Makoto Amaki, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Toshihisa Anzai, Satoshi Yasuda, Junjiro Kobayashi
Circulation journal : official journal of the Japanese Circulation Society, 82, 1, 289, 292, 25 Dec. 2017, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: The valve-in-valve procedure, in which a transcatheter heart valve (THV) is implanted over a prosthetic valve, has been shown to be safe and therapeutically effective, depending on the size of the replacement valve.Methods and Results:We report 3 cases of successful valve-in-valve procedure to replace a degenerated 19-mm stented prosthetic aortic valve. Balloon-expanding THVs were implanted: 20-mm in the 1st case and 23-mm in the next 2. Aortic stenosis was almost completely resolved in all patients, who recovered promptly and without cardiac adverse events. CONCLUSIONS: Using the valve-in-valve procedure for a 19-mm degenerated bioprosthesis was feasible and safe.

Coronary Artery Ectasia Predicts Future Cardiac Events in Patients With Acute Myocardial Infarction.
Takahito Doi, Yu Kataoka, Teruo Noguchi, Tatsuhiro Shibata, Takahiro Nakashima, Shoji Kawakami, Kazuhiro Nakao, Masashi Fujino, Toshiyuki Nagai, Tomoaki Kanaya, Yoshio Tahara, Yasuhide Asaumi, Etsuko Tsuda, Michikazu Nakai, Kunihiro Nishimura, Toshihisa Anzai, Kengo Kusano, Hiroaki Shimokawa, Yoichi Goto, Satoshi Yasuda
Arteriosclerosis, thrombosis, and vascular biology, 37, 12, 2350, 2355, Dec. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Rationale and Design of Low-dose Administration of Carperitide for Acute Heart Failure (LASCAR-AHF).
Toshiyuki Nagai, Yasuyuki Honda, Hiroki Nakano, Satoshi Honda, Naotsugu Iwakami, Atsushi Mizuno, Nobuyuki Komiyama, Takafumi Yamane, Yutaka Furukawa, Tadayoshi Miyagi, Syuzo Nishihara, Nobuhiro Tanaka, Taichi Adachi, Toshimitsu Hamasaki, Yasuhide Asaumi, Yoshio Tahara, Takeshi Aiba, Yasuo Sugano, Hideaki Kanzaki, Teruo Noguchi, Kengo Kusano, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
Cardiovascular drugs and therapy, 31, 5-6, 551, 557, Dec. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Cardiac Rehabilitation Increases Plasma Brain-Derived Neurotrophic Factor Levels in Patients With Heart Failure
Takashio Seiji, Goto Yoichi, Anzai Toshihisa, Tsujita Kenichi
CIRCULATION, 136, 14 Nov. 2017, [Peer-reviewed]

Diagnostic Utility of Cardiac Troponin T Levels in Patients With Infiltrative Cardiomyopathy
Takashio Seiji, Izumiya Yasuhiro, Hirakawa Kyoko, Marume Kyohei, Yamamoto Masahiro, Ueda Mitsuharu, Yamashita Taro, Ishibashi-Ueda Hatsue, Yasuda Satoshi, Ando Yukio, Anzai Toshihisa, Tsujita Kenichi
CIRCULATION, 136, 14 Nov. 2017, [Peer-reviewed]

Multimodality assessment of left ventricular dysfunction in Takayasu arteritis and familial hypercholesterolaemia.
Atsushi Okada, Hiroyuki Takahama, Masatsune Ogura, Yoshiaki Morita, Junichi Konma, Shuzo Yoshida, Shigeki Makino, Seiji Takashio, Makoto Amaki, Takahiro Ohara, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Mariko Harada-Shiba, Hatsue Ishibashi-Ueda, Satoshi Yasuda, Toshiaki Hanafusa, Toshihisa Anzai
ESC heart failure, 4, 4, 655, 659, Nov. 2017, [Peer-reviewed], [International Magazine]
English, Although left ventricular (LV) systolic dysfunction in patients suffering from Takayasu arteritis (TA) has been reported, little is known regarding the development of heart failure in these patients. We report a novel finding of active TA and familial hypercholesterolaemia presenting with severe LV dysfunction through multimodality assessments of LV systolic dysfunction.

Contrast-enhanced computed tomography with myocardial three-dimensional printing can guide treatment in symptomatic hypertrophic obstructive cardiomyopathy.
Yasuhiro Hamatani, Makoto Amaki, Hideaki Kanzaki, Kizuku Yamashita, Yasuteru Nakashima, Atsushi Shibata, Atsushi Okada, Hiroyuki Takahama, Takuya Hasegawa, Yusuke Shimahara, Yasuo Sugano, Tomoyuki Fujita, Isao Shiraishi, Satoshi Yasuda, Junjiro Kobayashi, Toshihisa Anzai
ESC heart failure, 4, 4, 665, 669, Nov. 2017, [Peer-reviewed], [International Magazine]
English, Both surgical myectomy and percutaneous transluminal septal myocardial ablation are effective treatments for drug-refractory symptomatic hypertrophic obstructive cardiomyopathy (HOCM). However, in some cases, it is not easy to elucidate the abnormal structure of left ventricular outflow obstruction to adopt these treatments. Here, we presented a young female patient with drug-refractory symptomatic HOCM. In this case, contrast-enhanced computed tomography enabled us to assess the suitability of percutaneous transluminal septal myocardial ablation. By creating three-dimensional printed models using computed tomography data, we could also visualize intracardiac structure and simulate the surgical procedure. A multimodality assessment strategy is useful for evaluating patients complicated with drug-refractory symptomatic HOCM.

What Should Be Generalized Diagnostic Markers for Peripartum Cardiomyopathy?
Ichiro Sakuma, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 81, 11, 1578, 1579, 25 Oct. 2017, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Potential palliative care quality indicators in heart disease patients: A review of the literature.
Atsushi Mizuno, Mitsunori Miyashita, Akitoshi Hayashi, Fujimi Kawai, Koichiro Niwa, Akemi Utsunomiya, Shun Kohsaka, Takashi Kohno, Takeshi Yamamoto, Morimasa Takayama, Toshihisa Anzai
Journal of cardiology, 70, 4, 335, 341, Oct. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Does the pathophysiology of heart failure prime the incidence of cancer?
Mari Sakamoto, Takuya Hasegawa, Masanori Asakura, Hideaki Kanzaki, Hiroyuki Takahama, Makoto Amaki, Naoki Mochizuki, Toshihisa Anzai, Toshimitsu Hamasaki, Masafumi Kitakaze
Hypertension research : official journal of the Japanese Society of Hypertension, 40, 9, 831, 836, Sep. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Earlier Right Ventricular Pacing in Cardiac Resynchronization Therapy for a Patient with Right Axis Deviation.
Yusuke Hattori, Kohei Ishibashi, Takashi Noda, Hideo Okamura, Hideaki Kanzaki, Toshihisa Anzai, Satoshi Yasuda, Kengo Kusano
Internal medicine (Tokyo, Japan), 56, 17, 2285, 2288, 01 Sep. 2017, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Efficacy and Safety of an Orally Administered Selective Prostacyclin Receptor Agonist, Selexipag, in Japanese Patients With Pulmonary Arterial Hypertension.
Nobuhiro Tanabe, Satoshi Ikeda, Nobuhiro Tahara, Keiichi Fukuda, Masaru Hatano, Hiroshi Ito, Tomotaka Nakayama, Toshihisa Anzai, Akiyoshi Hashimoto, Teruo Inoue, Kouji Kajinami, Yasuki Kihara, Hideyuki Kinoshita, Koichiro Kuwahara, Toyoaki Murohara, Osamu Okazaki, Satoshi Sakai, Toru Satoh, Yutaka Takeda, Yasuchika Takeishi, Mitsugu Taniguchi, Hiroshi Watanabe, Takeshi Yamamoto, Keiko Yamauchi-Takihara, Koichiro Yoshioka, Shigetake Sasayama
Circulation journal : official journal of the Japanese Circulation Society, 81, 9, 1360, 1367, 25 Aug. 2017, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Heart failure in patients with arrhythmogenic right ventricular cardiomyopathy: What are the risk factors?
Yoshitaka Kimura, Takashi Noda, Taka-Aki Matsuyama, Yosuke Otsuka, Tsukasa Kamakura, Mitsuru Wada, Kohei Ishibashi, Yuko Inoue, Koji Miyamoto, Hideo Okamura, Satoshi Nagase, Takeshi Aiba, Shiro Kamakura, Teruo Noguchi, Toshihisa Anzai, Kazuhiro Satomi, Yuko Wada, Seiko Ohno, Minoru Horie, Wataru Shimizu, Satoshi Yasuda, Hiroaki Shimokawa, Kengo Kusano
International journal of cardiology, 241, 288, 294, 15 Aug. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Impact of decreased serum albumin levels on acute kidney injury in patients with acute decompensated heart failure: a potential association of atrial natriuretic peptide.
Yoichi Takaya, Fumiki Yoshihara, Hiroyuki Yokoyama, Hideaki Kanzaki, Masafumi Kitakaze, Yoichi Goto, Toshihisa Anzai, Satoshi Yasuda, Hisao Ogawa, Yuhei Kawano, Kenji Kangawa
Heart and vessels, 32, 8, 932, 943, Aug. 2017, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

"Window Sliding" analysis combined with high-density and rapid electroanatomical mapping: its efficacy and the outcome of catheter ablation of atrial tachycardia.
Kosuke Nakasuka, Koji Miyamoto, Takashi Noda, Tsukasa Kamakura, Mitsuru Wada, Ikutaro Nakajima, Kohei Ishibashi, Yuko Inoue, Hideo Okamura, Satoshi Nagase, Takeshi Aiba, Shiro Kamakura, Wataru Shimizu, Teruo Noguchi, Toshihisa Anzai, Satoshi Yasuda, Nobuyuki Ohte, Kengo Kusano
Heart and vessels, 32, 8, 984, 996, Aug. 2017, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Prognostic impact of chronic total coronary occlusion on long-term outcomes in implantable cardioverter-defibrillator recipients with ischaemic heart disease.
Tatsuya Nishikawa, Masashi Fujino, Ikutaro Nakajima, Yasuhide Asaumi, Yu Kataoka, Toshihisa Anzai, Kengo Kusano, Teruo Noguchi, Yoichi Goto, Kunihiro Nishimura, Yoshihiro Miyamoto, Keisuke Kiso, Satoshi Yasuda
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 19, 7, 1153, 1162, 01 Jul. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Usefulness of the Direct and/or Total Bilirubin to Predict Adverse Outcomes in Patients With Acute Decompensated Heart Failure.
Atsushi Okada, Yasuo Sugano, Toshiyuki Nagai, Yasuyuki Honda, Naotsugu Iwakami, Hiroki Nakano, Seiji Takashio, Satoshi Honda, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Satoshi Yasuda, Toshihisa Anzai
The American journal of cardiology, 119, 12, 2035, 2041, 15 Jun. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

A Pathophysiological Role of Plasma Indoxyl Sulfate in Patients with Heart Failure
Miki Imazu, Hiroyuki Takahama, Kazuhiro Shindo, Takuya Hasegawa, Hideaki Kanzaki, Toshihisa Anzai, Hiroshi Asanuma, Toshisuke Morita, Masanori Asakura, Masafumi Kitakaze
INTERNATIONAL JOURNAL OF GERONTOLOGY, 11, 2, 62, 66, Jun. 2017, [Peer-reviewed]
English, Scientific journal

Clinical impact of the presence of macrophages in endomyocardial biopsies of patients with dilated cardiomyopathy.
Takafumi Nakayama, Yasuo Sugano, Tetsuro Yokokawa, Toshiyuki Nagai, Taka-Aki Matsuyama, Keiko Ohta-Ogo, Yoshihiko Ikeda, Hatsue Ishibashi-Ueda, Takeshi Nakatani, Nobuyuki Ohte, Satoshi Yasuda, Toshihisa Anzai
European journal of heart failure, 19, 4, 490, 498, Apr. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

機能性僧帽弁逆流に対する経カテーテル僧帽弁修復の役割(Role of Transcatheter Mitral Valve Repair for Functional Mitral Regurgitation)　　　　　　　　　　　　　　　
天木 誠, Hamatani Yasuhiro, Okada Atsushi, Takahama Hiroyuki, Hasegawa Takuya, Sugano Yasuo, Kanzaki Hideaki, Yasuda Satoshi, Anzai Toshihisa
日本循環器学会学術集会抄録集, 81回, RT4, 1, (一社)日本循環器学会, Mar. 2017
English

左室機能不全患者における心拍出量を推定するための代替法の最適利用(Optimal Application of Alternative Methods to Estimate Cardiac Output in Patients with Leftventricular Dysfunction)　　　　　　　　　　　　　　　
Hitsumoto Tatsuro, Hasegawa Takuya, Nakashima Yasuteru, Shibata Atsushi, Hamatani Yasuhiro, Okada Atsushi, Amaki Makoto, Takahama Hiroyuki, Sugano Yasuo, Kanzaki Hideaki, Yasuda Satoshi, Anzai Toshihisa
日本循環器学会学術集会抄録集, 81回, OE, 391, (一社)日本循環器学会, Mar. 2017
English

低体重は駆出率が保持された心不全における転帰の独立予測因子である JASPER試験からの報告(Underweight is an Independent Predictor of Outcomes in Heart Failure with Preserved Ejection Fraction: A Report from JASPER Study)　　　　　　　　　　　　　　　
Matsumoto Junichi, Kinugawa Shintaro, Fukushima Arata, Yokota Takashi, Yoshikawa Tsutomu, Saito Yoshihiko, Nagai Toshiyuki, Anzai Toshihisa
日本循環器学会学術集会抄録集, 81回, LBCS3, 6, (一社)日本循環器学会, Mar. 2017
English

Prognostic value of malnutrition assessed by Controlling Nutritional Status score for long-term mortality in patients with acute heart failure.
Naotsugu Iwakami, Toshiyuki Nagai, Toshiaki A Furukawa, Yasuo Sugano, Satoshi Honda, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
International journal of cardiology, 230, 529, 536, 01 Mar. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Impact of Elevated End-Diastolic Pulmonary Regurgitation Gradient on Worse Clinical Outcomes in Hospitalized Patients With Heart Failure.
Yasuyuki Honda, Toshiyuki Nagai, Yasuo Sugano, Satoshi Honda, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
The American journal of cardiology, 119, 4, 604, 610, 15 Feb. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Reply to "delirium in heart failure".
Satoshi Honda, Toshiyuki Nagai, Toshihisa Anzai
International journal of cardiology, 229, 133, 133, 15 Feb. 2017, [Peer-reviewed], [International Magazine]
English

Use of serum fibroblast growth factor 23 vs. plasma B-type natriuretic peptide levels in assessing the pathophysiology of patients with heart failure.
Miki Imazu, Hiroyuki Takahama, Makoto Amaki, Yasuo Sugano, Takahiro Ohara, Takuya Hasegawa, Hideaki Kanzaki, Toshihisa Anzai, Naoki Mochizuki, Hiroshi Asanuma, Masanori Asakura, Masafumi Kitakaze
Hypertension research : official journal of the Japanese Society of Hypertension, 40, 2, 181, 188, Feb. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Early development of acute kidney injury is an independent predictor of in-hospital mortality in patients with acute myocardial infarction.
Noriaki Moriyama, Masaharu Ishihara, Teruo Noguchi, Michio Nakanishi, Tetsuo Arakawa, Yasuhide Asaumi, Leon Kumasaka, Tomoaki Kanaya, Toshiyuki Nagai, Masashi Fujino, Satoshi Honda, Reiko Fujiwara, Toshihisa Anzai, Kengo Kusano, Yoichi Goto, Satoshi Yasuda, Shigeru Saito, Hisao Ogawa
Journal of cardiology, 69, 1, 79, 83, Jan. 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Persistent increase in cardiac troponin T at hospital discharge predicts repeat hospitalization in patients with acute decompensated heart failure.
Seiji Takashio, Toshiyuki Nagai, Yasuo Sugano, Satoshi Honda, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo F Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
PloS one, 12, 4, e0173336, 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Immunohistochemical identification of Propionibacterium acnes in granuloma and inflammatory cells of myocardial tissues obtained from cardiac sarcoidosis patients.
Naoya Asakawa, Keisuke Uchida, Mamoru Sakakibara, Kazunori Omote, Keiji Noguchi, Yusuke Tokuda, Kiwamu Kamiya, Kanako C Hatanaka, Yoshihiro Matsuno, Shiro Yamada, Kyoko Asakawa, Yuichiro Fukasawa, Toshiyuki Nagai, Toshihisa Anzai, Yoshihiko Ikeda, Hatsue Ishibashi-Ueda, Masanori Hirota, Makoto Orii, Takashi Akasaka, Kenta Uto, Yasushige Shingu, Yoshiro Matsui, Shin-Ichiro Morimoto, Hiroyuki Tsutsui, Yoshinobu Eishi
PloS one, 12, 7, e0179980, 2017, [Peer-reviewed], [International Magazine]
English, Scientific journal

Risk factors for amiodarone-induced thyroid dysfunction in Japan.
Sayoko Kinoshita, Tomohiro Hayashi, Kyoichi Wada, Mikie Yamato, Takeshi Kuwahara, Toshihisa Anzai, Mai Fujimoto, Kouichi Hosomi, Mitsutaka Takada
Journal of arrhythmia, 32, 6, 474, 480, Dec. 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: Amiodarone is associated with a number of significant adverse effects, including elevated transaminase levels, pulmonary fibrosis, arrhythmia, and thyroid dysfunction. Although thyroid dysfunction is considered to be a common and potentially serious adverse effect of amiodarone therapy, the exact pathogenesis remains unknown because of its complex manifestations. Therefore, the prevalence of, and risk factors for, amiodarone-induced thyroid dysfunction in Japanese patients were investigated in the present study. METHODS: A retrospective analysis of patients treated with amiodarone between January 2012 and December 2013 was performed. A total of 317 patients with euthyroidism, or subclinical hyperthyroidism or hypothyroidism, were enrolled in this study. RESULTS: After being treated with amiodarone, 30 (9.5%) and 60 patients (18.9%) developed amiodarone-induced hyperthyroidism and amiodarone-induced hypothyroidism, respectively. Ten (33.3%) patients with amiodarone-induced hyperthyroidism and 40 (66.6%) with amiodarone-induced hypothyroidism were diagnosed within two years of the initiation of amiodarone therapy. Dilated cardiomyopathy (DCM) [Adjusted odds ratio (OR) 3.30 (95% confidence interval (CI): 1.26-8.90)], and cardiac sarcoidosis [Adjusted OR 6.47 (95% CI: 1.60-25.77)] were identified as predictors of amiodarone-induced hyperthyroidism. The baseline free thyroxine (T4) level [Adjusted OR 0.13 (95% CI: 0.03-0.68)], and thyroid-stimulating hormone (TSH) level [Adjusted OR1.47 (95% CI: 1.26-1.74)] were identified as predictors of amiodarone-induced hypothyroidism. CONCLUSION: DCM and cardiac sarcoidosis were identified as risk factors for amiodarone-induced hyperthyroidism. Risk factors for amiodarone-induced hypothyroidism included higher baseline TSH level and lower baseline free T4 level, suggesting that subclinical hypothyroidism may be a potential risk factor for the development of amiodarone-induced hypothyroidism.

Myocardial Immunocompetent Cells and Macrophage Phenotypes as Histopathological Surrogates for Diagnosis of Cardiac Sarcoidosis in Japanese.
Yasuyuki Honda, Toshiyuki Nagai, Yoshihiko Ikeda, Mamoru Sakakibara, Naoya Asakawa, Nobutaka Nagano, Michikazu Nakai, Kunihiro Nishimura, Yasuo Sugano, Keiko Ohta-Ogo, Yasuhide Asaumi, Takeshi Aiba, Hideaki Kanzaki, Kengo Kusano, Teruo Noguchi, Satoshi Yasuda, Hiroyuki Tsutsui, Hatsue Ishibashi-Ueda, Toshihisa Anzai
Journal of the American Heart Association, 5, 11, 17 Nov. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Non-linear Equation using Plasma Brain Natriuretic Peptide Levels to Predict Cardiovascular Outcomes in Patients with Heart Failure.
Hiroki Fukuda, Hideaki Suwa, Atsushi Nakano, Mari Sakamoto, Miki Imazu, Takuya Hasegawa, Hiroyuki Takahama, Makoto Amaki, Hideaki Kanzaki, Toshihisa Anzai, Naoki Mochizuki, Akira Ishii, Hiroshi Asanuma, Masanori Asakura, Takashi Washio, Masafumi Kitakaze
Scientific reports, 6, 37073, 37073, 15 Nov. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Abstract 13881: Determining Factors and Prognostic Value of Plasma γ- Atrial Natriuretic Peptide Ratio in Patients With Heart Failure
Seiji Takashio, Hiroyuki Takahama, Tomohiro Hayashi, Chiaki Nagai-Okatani,, Toshio Nishikimi, Yasuaki Nakagawa, Makoto Amaki, Takahiro Ohara, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Satoshi Yasuda, Kenji Kangawa, Naoto Minamino, Toshihisa Anzai
Circulation, 11 Nov. 2016
Scientific journal

Prevalence, determinants, and prognostic significance of delirium in patients with acute heart failure.
Satoshi Honda, Toshiyuki Nagai, Yasuo Sugano, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
International journal of cardiology, 222, 521, 527, 01 Nov. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Risk stratification based on nutritional screening on admission: Three-year clinical outcomes in hospitalized patients with acute heart failure syndrome.
Masashi Fujino, Hiroyuki Takahama, Toshimitsu Hamasaki, Kenichi Sekiguchi, Kengo Kusano, Toshihisa Anzai, Teruo Noguchi, Yoichi Goto, Masafumi Kitakaze, Hiroyuki Yokoyama, Hisao Ogawa, Satoshi Yasuda
Journal of cardiology, 68, 5, 392, 398, Nov. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

The Current Status of Cardiovascular Medicine in Japan - Analysis of a Large Number of Health Records From a Nationwide Claim-Based Database, JROAD-DPC.
Satoshi Yasuda, Kazuhiro Nakao, Kunihiro Nishimura, Yoshihiro Miyamoto, Yoko Sumita, Toshiaki Shishido, Toshihisa Anzai, Hiroyuki Tsutsui, Hiroshi Ito, Issei Komuro, Yoshihiko Saito, Hisao Ogawa
Circulation journal : official journal of the Japanese Circulation Society, 80, 11, 2327, 2335, 25 Oct. 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Potentially Lethal Ventricular Arrhythmias and Heart Failure in Arrhythmogenic Right Ventricular Cardiomyopathy: What Are the Differences Between Men and Women?
Yoshitaka Kimura, Takashi Noda, Yosuke Otsuka, Mitsuru Wada, Ikutaro Nakajima, Kohei Ishibashi, Koji Miyamoto, Hideo Okamura, Takeshi Aiba, Shiro Kamakura, Teruo Noguchi, Toshihisa Anzai, Kazuhiro Satomi, Hisao Ogawa, Satoshi Yasuda, Kengo F Kusano
JACC. Clinical electrophysiology, 2, 5, 546, 555, Oct. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal, OBJECTIVES: The aim of this study was to assess sex-related differences in sporadic cases of arrhythmogenic right ventricular cardiomyopathy (ARVC). BACKGROUND: Previous studies have suggested male predominance in ARVC. However, the impact of sex on the heterogeneous clinical profile and prognosis of ARVC were not fully recognized. METHODS: The study population included 110 patients with ARVC who fulfilled the revised Task Force criteria (median age 48 years [interquartile range (IQR): 36 to 57 years]). All patients were sporadic cases without family history of ARVC. Male patients had a 3:1 predominance (75%). Ninety-seven patients (88%) were considered to have "definite" ARVC based on revised Task Force criteria. RESULTS: At the initial evaluation, there were no significant sex-related differences in age, 12-lead electrocardiogram findings, late potentials by signal-averaged electrocardiogram, left ventricular ejection fraction, or right ventricular ejection fraction. During a median follow-up of 10.0 years (IQR: 5.2 to 15.6 years), 18 patients died from cardiac causes. Kaplan-Meier analysis, considering patients' lives since birth, revealed that male patients had a significantly higher risk of ventricular tachycardia/ventricular fibrillation than did female patients (56% vs. 90%, p = 0.02), whereas female patients had a significantly higher risk of heart failure (HF) death or heart transplantation (22% vs. 5%, p = 0.002). On multivariate Cox regression analysis, female sex was an independent risk factor for HF death or heart transplantation due to HF (hazard ratio: 6.29, 95% confidence interval: 1.29 to 40.2; p = 0.02). CONCLUSIONS: Among patients with sporadic ARVC, men had a significantly higher risk of ventricular tachycardia/ventricular fibrillation, whereas women had a significantly higher risk of HF death or heart transplantation due to HF.

Diagnostic Value of Right Ventricular Dysfunction in Tachycardia-Induced Cardiomyopathy Using Cardiac Magnetic Resonance Imaging.
Atsushi Okada, Ikutaro Nakajima, Yoshiaki Morita, Yuko Y Inoue, Tsukasa Kamakura, Mitsuru Wada, Kohei Ishibashi, Koji Miyamoto, Hideo Okamura, Satoshi Nagase, Takashi Noda, Takeshi Aiba, Shiro Kamakura, Toshihisa Anzai, Teruo Noguchi, Satoshi Yasuda, Kengo Kusano
Circulation journal : official journal of the Japanese Circulation Society, 80, 10, 2141, 8, 23 Sep. 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Validation of the Coronary Artery Bypass Graft SYNTAX Score (Synergy Between Percutaneous Coronary Intervention With Taxus) as a Prognostic Marker for Patients With Previous Coronary Artery Bypass Graft Surgery After Percutaneous Coronary Intervention.
Tadayoshi Miyagi, Yasuhide Asaumi, Kunihiro Nishimura, Takahiro Nakashima, Hiroki Sakamoto, Kazuhiro Nakao, Tomoaki Kanaya, Toshiyuki Nagai, Yuji Shimabukuro, Yoshihiro Miyamoto, Tomoyuki Fujita, Kengo Kusano, Toshihisa Anzai, Junjirou Kobayashi, Teruo Noguchi, Hisao Ogawa, Satoshi Yasuda
Circulation. Cardiovascular interventions, 9, 9, Sep. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Subclinical hypothyroidism is an independent predictor of adverse cardiovascular outcomes in patients with acute decompensated heart failure.
Tomohiro Hayashi, Takuya Hasegawa, Hideaki Kanzaki, Akira Funada, Makoto Amaki, Hiroyuki Takahama, Takahiro Ohara, Yasuo Sugano, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
ESC heart failure, 3, 3, 168, 176, Sep. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIMS: Altered thyroid hormone metabolism characterized by a low triiodothyronine (T3), so-called low-T3 syndrome, is a common finding in patients with severe systemic diseases. Additionally, subclinical thyroid dysfunction, defined as abnormal thyroid stimulating hormone (TSH) and normal thyroxine (T4), causes left ventricular dysfunction. Our objective was to identify the prevalence and prognostic impact of low-T3 syndrome and subclinical thyroid dysfunction in patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: We examined 274 ADHF patients who were not receiving thyroid medication or amiodarone on admission (70 ± 15 years, 156 male), who underwent thyroid function tests. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L; subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L; and subclinical hyperthyroidism as TSH < 0.45 mIU/L, with normal free T4 level for the last two. Additionally, low-T3 syndrome was defined as free T3 < 4.0 pmol/L among euthyroidism subjects. On admission, 188 patients (69%) showed euthyroidism, 58 (21%) subclinical hypothyroidism, 5 (2%) subclinical hyperthyroidism, and 95 (35%) low-T3 syndrome. Cox proportional hazards models revealed that higher TSH, but not free T3 and free T4, was independently associated with composite cardiovascular events, including cardiac death and re-hospitalization for heart failure. Indeed, subclinical hypothyroidism was an independent predictor (hazard ratio: 2.31; 95% confidence interval: 1.44 to 3.67; P < 0.001), whereas low-T3 syndrome and subclinical hyperthyroidism were not. CONCLUSIONS: Subclinical hypothyroidism on admission was an independent predictor of adverse cardiovascular outcomes in ADHF patients, suggesting a possible interaction between thyroid dysfunction and the pathophysiology of ADHF.

Usefulness of Geriatric Nutritional Risk Index for Assessing Nutritional Status and Its Prognostic Impact in Patients Aged ≥65 Years With Acute Heart Failure.
Yasuyuki Honda, Toshiyuki Nagai, Naotsugu Iwakami, Yasuo Sugano, Satoshi Honda, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
The American journal of cardiology, 118, 4, 550, 5, 15 Aug. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Impact of B-type natriuretic peptide (BNP) on development of atrial fibrillation in people with Type 2 diabetes
I. Kishimoto, H. Makino, Y. Ohata, T. Tamanaha, M. Tochiya, K. Kusano, T. Anzai, K. Toyoda, S. Yasuda, K. Minematsu, H. Ogawa
Diabetic Medicine, 33, 8, 1118, 1124, 01 Aug. 2016
Scientific journal

[NYHA functional classification and AHA/ACC Stages for heart failure management].
Nagai T, Anzai T
Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology, 74 Suppl 6, 340, 344, Aug. 2016, [Peer-reviewed]

[NYHA functional classification and AHA/ACC Stages for heart failure management].
Toshiyuki Nagai, Toshihisa Anzai
Nihon rinsho. Japanese journal of clinical medicine, 74 Suppl 6, 340, 4, Aug. 2016, [Peer-reviewed], [Domestic magazines]
Japanese, Scientific journal

Larger low voltage zone in endocardial unipolar map compared with that in epicardial bipolar map indicates difficulty in eliminating ventricular tachycardia by catheter ablation.
Koji Miyamoto, Takashi Noda, Kazuhiro Satomi, Mitsuru Wada, Ikutaro Nakajima, Kohei Ishibashi, Hideo Okamura, Teruo Noguchi, Toshihisa Anzai, Satoshi Yasuda, Hisao Ogawa, Wataru Shimizu, Takeshi Aiba, Shiro Kamakura, Kengo Kusano
Heart and vessels, 31, 8, 1337, 46, Aug. 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Impact of renal function deterioration on adverse events during anticoagulation therapy using non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.
Koji Miyamoto, Takeshi Aiba, Shoji Arihiro, Makoto Watanabe, Yoshihiro Kokubo, Kohei Ishibashi, Sayako Hirose, Mitsuru Wada, Ikutaro Nakajima, Hideo Okamura, Takashi Noda, Kazuyuki Nagatsuka, Teruo Noguchi, Toshihisa Anzai, Satoshi Yasuda, Hisao Ogawa, Shiro Kamakura, Wataru Shimizu, Yoshihiro Miyamoto, Kazunori Toyoda, Kengo Kusano
Heart and vessels, 31, 8, 1327, 36, Aug. 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Inflammatory dilated cardiomyopathy　　　　　　　　　　　　　　　
Yasuo Sugano, Toshihisa Anzai
Respiration and Circulation, 64, 7, 655, 661, Igaku-Shoin Ltd, 01 Jul. 2016
Japanese, Scientific journal

Novel chemiluminescent enzyme immunoassays for individual quantification of three endogenous molecular forms of atrial natriuretic peptide in human plasma.
Nagai-Okatani C, Kangawa K, Takashio S, Takahama H, Hayashi T, Anzai T, Minamino N
The Journal of Applied Laboratory Medicine, 1, 1, 47, 59, Jul. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are cardiac peptide hormones with pivotal roles in maintaining cardiovascular homeostasis. BNP and its precursor fragment are accepted as gold standard markers for heart failure (HF). Human ANP is present in the atria of the heart and plasma as 3 endogenous molecular forms designated α-ANP, β-ANP, and proANP. A previous study indicated that the ratios of these 3 ANP forms are altered in the plasma of HF patients. The purpose of our study was to establish immunoassays for quantifying the individual ANP forms to collect clinical information. METHODS: We developed 3 plate-based chemiluminescent enzyme immunoassays (CLEIAs) for measuring total ANP (i.e., sum of α-ANP, β-ANP, and proANP), β-ANP, and proANP levels. To minimize background signals, we added single-step PEGylation targeting the immobilized antibody in the conventional plate-based sandwich CLEIA procedure. RESULTS: CLEIAs with PEGylation showed sensitivity, specificity, reproducibility, and accuracy satisfying clinical requirements. Two of the CLEIAs enabled direct measurement in plasma samples. During treatments, acute decompensated HF patients exhibited marked decreases in plasma β-ANP levels but moderate decreases in plasma proANP level. The plasma ratios of α-ANP/total ANP and proANP/total ANP in acute decompensated HF patients were maintained, whereas the β-ANP/total ANP ratio was significantly decreased at discharge. CONCLUSIONS: The combination of the 3 CLEIAs enabled accurate quantification of α-ANP, β-ANP, and proANP, even in plasma samples, and indicated the potential of β-ANP and proANP as circulating biomarkers for HF, with different characteristics from that of BNP.

Renovascular heart failure: heart failure in patients with atherosclerotic renal artery disease.
Osami Kawarada, Satoshi Yasuda, Teruo Noguchi, Toshihisa Anzai, Hisao Ogawa
Cardiovascular intervention and therapeutics, 31, 3, 171, 82, Jul. 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, Atherosclerotic renal artery disease presents with a broad spectrum of clinical features, including heart failure as well as hypertension, and renal failure. Although recent randomized controlled trials failed to demonstrate renal artery stenting can reduce blood pressure or the number of cardiovascular or renal events more so than medical therapy, increasing attention has been paid to flash pulmonary edema and congestive heart failure associated with atherosclerotic renal artery disease. This clinical entity "renovascular heart failure" is diagnosed retrospectively. Given the increasing global burden of heart failure, this review highlights the background and catheter-based therapeutic aspects for renovascular heart failure.

Prognostic significance of endogenous erythropoietin in long-term outcome of patients with acute decompensated heart failure.
Toshiyuki Nagai, Kunihiro Nishimura, Takehiro Honma, Aya Higashiyama, Yasuo Sugano, Michikazu Nakai, Satoshi Honda, Naotsugu Iwakami, Atsushi Okada, Shoji Kawakami, Tomoaki Kanaya, Yasuhide Asaumi, Takeshi Aiba, Yoko Nishida, Yoshimi Kubota, Daisuke Sugiyama, Tomonori Okamura, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
European journal of heart failure, 18, 7, 803, 13, Jul. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

The predictability of renin-angiotensin-aldosterone system factors for clinical outcome in patients with acute decompensated heart failure.
Yasuki Nakada, Hiroyuki Takahama, Hideaki Kanzaki, Yasuo Sugano, Takuya Hasegawa, Takahiro Ohara, Makoto Amaki, Akira Funada, Akemi Yoshida, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
Heart and vessels, 31, 6, 925, 31, Jun. 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Prognostic significance of late gadolinium enhancement quantification in cardiac magnetic resonance imaging of hypertrophic cardiomyopathy with systolic dysfunction.
Akira Funada, Hideaki Kanzaki, Teruo Noguchi, Yoshiaki Morita, Yasuo Sugano, Takahiro Ohara, Takuya Hasegawa, Hiromi Hashimura, Hatsue Ishibashi-Ueda, Masafumi Kitakaze, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
Heart and vessels, 31, 5, 758, 70, May 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Erratum to: Prognostic significance of late gadolinium enhancement quantification in cardiac magnetic resonance imaging of hypertrophic cardiomyopathy with systolic dysfunction.
Akira Funada, Hideaki Kanzaki, Teruo Noguchi, Yoshiaki Morita, Yasuo Sugano, Takahiro Ohara, Takuya Hasegawa, Hiromi Hashimura, Hatsue Ishibashi-Ueda, Masafumi Kitakaze, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
Heart and vessels, 31, 5, 771, 772, May 2016, [Peer-reviewed], [Domestic magazines]
English

Exhaled Acetone Concentration Is Related to Hemodynamic Severity in Patients With Non-Ischemic Chronic Heart Failure.
Tetsuro Yokokawa, Yasuo Sugano, Akito Shimouchi, Atsushi Shibata, Naoya Jinno, Toshiyuki Nagai, Hideaki Kanzaki, Takeshi Aiba, Kengo Kusano, Mikiyasu Shirai, Yasuchika Takeishi, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 80, 5, 1178, 86, 25 Apr. 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Rationale and design of a randomized trial to test the safety and non-inferiority of canagliflozin in patients with diabetes with chronic heart failure: the CANDLE trial.
Atsushi Tanaka, Teruo Inoue, Masafumi Kitakaze, Jun-Ichi Oyama, Masataka Sata, Isao Taguchi, Wataru Shimizu, Hirotaka Watada, Hirofumi Tomiyama, Junya Ako, Yasushi Sakata, Toshihisa Anzai, Masaaki Uematsu, Makoto Suzuki, Kazuo Eguchi, Akira Yamashina, Yoshihiko Saito, Yasunori Sato, Shinichiro Ueda, Toyoaki Murohara, Koichi Node
Cardiovascular diabetology, 15, 57, 57, 04 Apr. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Significance of myocardial tenascin-C expression in left ventricular remodelling and long-term outcome in patients with dilated cardiomyopathy.
Tetsuro Yokokawa, Yasuo Sugano, Takafumi Nakayama, Toshiyuki Nagai, Taka-Aki Matsuyama, Keiko Ohta-Ogo, Yoshihiko Ikeda, Hatsue Ishibashi-Ueda, Takeshi Nakatani, Satoshi Yasuda, Yasuchika Takeishi, Hisao Ogawa, Toshihisa Anzai
European journal of heart failure, 18, 4, 375, 85, Apr. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Practical applicability of landiolol, an ultra-short-acting β1-selective blocker, for rapid atrial and ventricular tachyarrhythmias with left ventricular dysfunction.
Yuko Wada, Takeshi Aiba, Yasuyuki Tsujita, Hideki Itoh, Mitsuru Wada, Ikutaro Nakajima, Kohei Ishibashi, Hideo Okamura, Koji Miyamoto, Takashi Noda, Yasuo Sugano, Hideaki Kanzaki, Toshihisa Anzai, Kengo Kusano, Satoshi Yasuda, Minoru Horie, Hisao Ogawa
Journal of arrhythmia, 32, 2, 82, 8, Apr. 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, BACKGROUND: Landiolol effectively controls rapid heart rate in atrial fibrillation or flutter (AF/AFL) patients with left ventricular (LV) dysfunction. However, predicting landiolol Responders and Non-Responders and patients who will experience adverse effects remains a challenge. The aim of this study was to clarify the potential applicability of landiolol for rapid AF/AFL and refractory ventricular tachyarrhythmias (VTs) in patients with heart failure. METHODS: A total of 39 patients with AF/AFL with ventricular response ≥120 bpm and 12 VTs were retrospectively enrolled. Landiolol Responders for rapid AF/AFL were defined as patients whose ventricular response was suppressed to less than 110 bpm or decreased by ≥20% from the initial heart rate after administration of landiolol. Responders for VTs were defined as patients with no recurrent VTs during the 24 h after the initiation of landiolol. RESULTS: For AF/AFL, 29 patients (74%) were Responders. In nine patients (31%), AF was spontaneously terminated after starting landiolol. Eight Non-Responders (80%) needed to have AF terminated by cardioversion. Left ventricular ejection fraction (LVEF) at baseline was significantly associated with landiolol efficacy. For VTs, seven patients (58%) were Responders, and smaller LV diastolic and systolic diameters were associated with landiolol efficacy. Hypotension after landiolol treatment occurred in 5 of 51 patients, and lower LV systolic function was associated with the development of adverse events. CONCLUSIONS: Landiolol is effective in patients with heart failure not only due to rapid AF/AFL but also due to VTs. However, preserved LVEF is important for efficacy and safety in landiolol treatment.

Effect of Discontinuation of Prednisolone Therapy on Risk of Cardiac Mortality Associated With Worsening Left Ventricular Dysfunction in Cardiac Sarcoidosis.
Toshiyuki Nagai, Nobutaka Nagano, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Hideaki Kanzaki, Kengo Kusano, Teruo Noguchi, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
The American journal of cardiology, 117, 6, 966, 71, 15 Mar. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

コホート研究・臨床試験から見えてきたHFpEFの課題 全国レジストリJASPER Studyに基づく駆出率の保たれた心不全入院患者の国際比較(Unsolved Issues in Heart Failure with Preserved Ejection Fraction (HFpEF) Based on Cohort Studies and Clinical Trials International Comparison of Hospitalized Patients with Heart Failure with Preserved Ejection Fraction Based on Nationwide Registry-JASPER Study)　　　　　　　　　　　　　　　
Anzai Toshihisa, Nagai Toshiyuki, Sugano Yasuo, Takashio Seiji, Takahama Hiroyuki, Ohhara Takahiro, Kanzaki Hideaki, Noguchi Teruo, Kusano Kengo, Yasuda Satoshi, Saito Yoshihiko, Yoshikawa Tsutomu, Ogawa Hisao
Circulation Journal, 80, Suppl.I, 144, 144, (一社)日本循環器学会, Mar. 2016
English

心臓再同期療法が拡張型心筋症に続発する僧帽弁閉鎖不全に与える長期効果(Long-term Effects of Cardiac Resynchronization Therapy on Mitral Regurgitation Secondary to Dilated Cardiomyopathy)　　　　　　　　　　　　　　　
Kanzaki Hideaki, Noda Takashi, Amaki Makoto, Ohhara Takahiro, Takahama Hiroyuki, Hasegawa Takuya, Sugano Yasuo, Kusano Kengo, Kitakaze Masafumi, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 80, Suppl.I, 1482, 1482, (一社)日本循環器学会, Mar. 2016
English

心臓MRIにより評価した特発性拡張型心筋症患者における左右間の心室機能の関連性(Relation between Left and Right Ventricular Function in Patients with Idiopathic Dilated Cardiomyopathy Assessed by Cardiac Magnetic Resonance Imaging)　　　　　　　　　　　　　　　
Yamamoto Asuka, Amaki Makoto, Tateishi Emi, Kanzaki Hideaki, Takashio Seiji, Takahama Hiroyuki, Ohhara Takahiro, Hasegawa Takuya, Sugano Yasuo, Morita Toshiaki, Noguchi Teruo, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 80, Suppl.I, 2001, 2001, (一社)日本循環器学会, Mar. 2016
English

地域ベース集団でステージAとされた対象者における不顕性左室機能障害(Subclinical Left Ventricular Dysfunction in Stage A Subjects in a Community-based Population)　　　　　　　　　　　　　　　
Hasegawa Takuya, Asakura Masanori, Kanzaki Hideaki, Sakamoto Mari, Asanuma Hiroshi, Takashio Seiji, Amaki Makoto, Takahama Hiroyuki, Ohhara Takahiro, Sugano Yasuo, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa, Kitakaze Masafumi
Circulation Journal, 80, Suppl.I, 2489, 2489, (一社)日本循環器学会, Mar. 2016
English

心不全患者における血漿γ-atrial natriuretic peptide比の決定因子(Determining Factor of Plasma γ-Atrial Natriuretic Peptide Ratio in Patients with Heart Failure)　　　　　　　　　　　　　　　
Takashio Seiji, Takahama Hiroyuki, Minamino Naoto, Nagai Chiaki, Hayashi Tomohiro, Kanzaki Hideaki, Sugano Yasuo, Hasegawa Takuya, Ohhara Takahiro, Amaki Makoto, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 80, Suppl.I, 2505, 2505, (一社)日本循環器学会, Mar. 2016
English

非虚血性拡張型心筋症患者において運動中に明らかになる左房機能は運動耐容能の主要な決定因子である(Unmasked Left Atrial Function during Exercise is a Key Determinant of Exercise Capacity in Patients with Non-ischemic Dilated Cardiomyopathy)　　　　　　　　　　　　　　　
Amaki Makoto, Kanzaki Hideaki, Takashio Seiji, Takahama Hiroyuki, Ohhara Takahiro, Hasegawa Takuya, Sugano Yasuo, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 80, Suppl.I, 2962, 2962, (一社)日本循環器学会, Mar. 2016
English

特発性拡張型心筋症患者において右室および左室全体の縦方向ストレインは運動耐容能の強力な予測因子である(Right and Left Ventricular Global Longitudinal Strains are Powerful Predictors of Exercise Capacity in Patients with Idiopathic Dilated Cardiomyopathy)　　　　　　　　　　　　　　　
Yamamoto Asuka, Amaki Makoto, Tateishi Emi, Kanzaki Hideaki, Takashio Seiji, Takahama Hiroyuki, Ohhara Takahiro, Hasegawa Takuya, Sugano Yasuo, Morita Toshiaki, Noguchi Teruo, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 80, Suppl.I, 2963, 2963, (一社)日本循環器学会, Mar. 2016
English

Intracardiac echocardiography to diagnose pannus formation after aortic valve replacement.
Yoshiya Yamamoto, Takahiro Ohara, Akira Funada, Hiroyuki Takahama, Makoto Amaki, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Toshihisa Anzai
Journal of echocardiography, 14, 1, 39, 41, Mar. 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, A 66-year-old female, under regular follow-up for 20 years after aortic valve replacement (19-mm Carbomedics), presented dyspnea on effort and hypotension during hemodialysis. A transthoracic echocardiogram showed elevation of transvalvular velocity up to 4 m/s, but the structure around the aortic prosthesis was difficult to observe due to artifacts. Fluoroscopy revealed normal motion of the leaflets of the mechanical valve. Intracardiac echocardiography (ICE) revealed a pannus-like structure in the left ventricular outflow tract. Transesophageal echocardiogram also revealed this structure. ICE can visualize structural abnormalities around a prosthetic valve after cardiac surgery even in patients in whom conventional imaging modalities failed.

[Valvular Heart Disease: Current Treatment and Future Perspectives. Editorial: Paradigm shift and future aspect of the treatment of valvular heart disease].
Toshihisa Anzai
Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine, 105, 2, 181, 3, 10 Feb. 2016, [Peer-reviewed], [Domestic magazines]
Japanese

Response to Letter Regarding Article, "Prevalence, Clinical Features, and Prognosis of Acute Myocardial Infarction Attributable to Coronary Artery Embolism".
Teruo Noguchi, Satoshi Yasuda, Tatsuhiro Shibata, Shoji Kawakami, Tomotaka Tanaka, Yasuhide Asaumi, Tomoaki Kanaya, Toshiyuki Nagai, Kazuhiro Nakao, Masashi Fujino, Kazuyuki Nagatsuka, Hatsue Ishibashi-Ueda, Kunihiro Nishimura, Yoshihiro Miyamoto, Kengo Kusano, Toshihisa Anzai, Yoichi Goto, Hisao Ogawa
Circulation, 133, 5, e379, E379, 02 Feb. 2016, [Peer-reviewed], [International Magazine]
English

A case of acute decompensated heart failure evaluated by series of exhaled acetone concentrations as noninvasive biomarker of heart failure severity.
Tetsuro Yokokawa, Yasuo Sugano, Akito Shimouchi, Atsushi Shibata, Takafumi Nakayama, Takahiro Ohara, Naoya Jinno, Hideaki Kanzaki, Toshihisa Anzai
International journal of cardiology, 204, 112, 3, 01 Feb. 2016, [Peer-reviewed], [International Magazine]
English

Impact of onset time of acute kidney injury on outcomes in patients with acute decompensated heart failure.
Yoichi Takaya, Fumiki Yoshihara, Hiroyuki Yokoyama, Hideaki Kanzaki, Masafumi Kitakaze, Yoichi Goto, Toshihisa Anzai, Satoshi Yasuda, Hisao Ogawa, Yuhei Kawano
Heart and vessels, 31, 1, 60, 5, Jan. 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Prognostic Impact of Functional Mitral Regurgitation in Patients Admitted With Acute Decompensated Heart Failure.
Yuko Wada, Takahiro Ohara, Akira Funada, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Hiroyuki Yokoyama, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 80, 1, 139, 47, 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Pronounced Shortening of QT Interval With Mexiletine Infusion Test in Patients With Type 3 Congenital Long QT Syndrome.
Moritoshi Funasako, Takeshi Aiba, Kohei Ishibashi, Ikutaro Nakajima, Koji Miyamoto, Yuko Inoue, Hideo Okamura, Takashi Noda, Shiro Kamakura, Toshihisa Anzai, Teruo Noguchi, Satoshi Yasuda, Yoshihiro Miyamoto, Kengo Fukushima Kusano, Hisao Ogawa, Wataru Shimizu
Circulation journal : official journal of the Japanese Circulation Society, 80, 2, 340, 5, 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

First Case Report of the Antemortem Diagnosis of Nonbacterial Thrombotic Endocarditis of a Mechanical Prosthetic Valve.
Hideki Yasutake, Yasuo Sugano, Yoshihiko Ikeda, Takahiro Ohara, Takuya Hasegawa, Hideaki Kanzaki, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 55, 3, 255, 7, 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Prognostic Value of Prothrombin Time International Normalized Ratio in Acute Decompensated Heart Failure - A Combined Marker of Hepatic Insufficiency and Hemostatic Abnormality.
Atsushi Okada, Yasuo Sugano, Toshiyuki Nagai, Seiji Takashio, Satoshi Honda, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo F Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 80, 4, 913, 23, 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Prosthetic Valve Dysfunction 35 Years after Mitral Valve Replacement with a Starr-Edwards Caged-disc Valve.
Tetsuro Yokokawa, Takahiro Ohara, Seiji Takashio, Mari Sakamoto, Yuko Wada, Kenji Nakamura, Hiroyuki Takahama, Makoto Amaki, Takuya Hasegawa, Yasuo Sugano, Hideaki Kanzaki, Satoshi Yasuda, Hisao Ogawa, Tomoyuki Fujita, Junjiro Kobayashi, Yoko Okamoto, Taka-Aki Matsuyama, Hatsue Ishibashi-Ueda, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 55, 5, 479, 83, 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Pathohistological Evidence of Smoldering Inflammation in Rheumatic Heart Disease with Massive Left Atrial Calcification.
Mikio Shiba, Yasuo Sugano, Yoshihiko Ikeda, Hatsue Ishibashi-Ueda, Takahiro Ohara, Takuya Hasegawa, Hideaki Kanzaki, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 55, 7, 751, 4, 2016, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Pathological Investigation of Congenital Bicuspid Aortic Valve Stenosis, Compared with Atherosclerotic Tricuspid Aortic Valve Stenosis and Congenital Bicuspid Aortic Valve Regurgitation.
Yasuhiro Hamatani, Hatsue Ishibashi-Ueda, Toshiyuki Nagai, Yasuo Sugano, Hideaki Kanzaki, Satoshi Yasuda, Tomoyuki Fujita, Junjiro Kobayashi, Toshihisa Anzai
PloS one, 11, 8, e0160208, 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Circulating Omega-6, But Not Omega-3 Polyunsaturated Fatty Acids, Are Associated with Clinical Outcomes in Patients with Acute Decompensated Heart Failure.
Toshiyuki Nagai, Yasuyuki Honda, Yasuo Sugano, Kunihiro Nishimura, Michikazu Nakai, Satoshi Honda, Naotsugu Iwakami, Atsushi Okada, Yasuhide Asaumi, Takeshi Aiba, Teruo Noguchi, Kengo Kusano, Hisao Ogawa, Satoshi Yasuda, Toshihisa Anzai
PloS one, 11, 11, e0165841, 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal

Azilsartan, but not Candesartan Improves Left Ventricular Diastolic Function in Patients with Hypertension and Heart Failure
Mari Sakamoto, Masanori Asakura, Atsushi Nakano, Hideaki Kanzaki, Yasuo Sugano, Makoto Amaki, Takahiro Ohara, Takuya Hasegawa, Toshihisa Anzai, Masafumi Kitakaze
INTERNATIONAL JOURNAL OF GERONTOLOGY, 9, 4, 201, 205, Dec. 2015, [Peer-reviewed]
English, Scientific journal

Improvement of left ventricular filling and pulmonary artery pressure following unilateral renal artery total occlusion stenting in a patient with recurrent congestive heart failure complicated by renovascular hypertension and renal failure.
Osami Kawarada, Ryota Kitajima, Yasuo Sugano, Teruo Noguchi, Toshihisa Anzai, Hisao Ogawa, Satoshi Yasuda
ESC heart failure, 2, 4, 160, 163, Dec. 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal, Recurrent congestive heart failure related to renal artery disease is an important clinical entity that is typically observed in bilateral renal artery stenosis or solitary functioning kidney. However, the relationship between heart failure and unilateral renal artery disease, especially that with total occlusion, remains unclear. We report a successful management by unilateral renal artery total occlusion stenting with an evidence of improvement of left ventricular filling and pulmonary artery pressure in case of a patient suffering from medical therapy resistant recurrent congestive heart failure with preserved ejection fraction.

Active cardiac sarcoidosis in a patient with adult-onset Kawasaki disease.
Noriaki Moriyama, Takahiro Ohara, Hideaki Kanzaki, Etsuko Tsuda, Masaharu Ishihara, Toshihisa Anzai
Journal of cardiology cases, 12, 3, 68, 71, Sep. 2015, [Peer-reviewed], [Domestic magazines]
English, Adult-onset Kawasaki disease is a rare condition. Cardiac sarcoidosis is an uncommon cardiomyopathy which is characterized by progressive cardiac dysfunction, and abnormality on electrocardiography and morphological aberration of the heart. We report a first case of a combination of these rare conditions. The patient was initially diagnosed with Kawasaki disease based on the coronary artery aneurysms and a past medical history at the age of 20 years which was typical of Kawasaki disease. Decades later, he developed progressive cardiac dysfunction and a sudden-onset atrioventricular block. Laboratory and imaging results revealed severe myocardial damage and inflammation which were unexplainable by coronary artery ischemia. We diagnosed him with cardiac sarcoidosis based on a Japanese guideline to diagnose cardiac sarcoidosis. A cardiac resynchronization therapy defibrillator was implanted and he received oral steroid therapy. This rare combination of adult-onset Kawasaki disease and cardiac sarcoidosis may suggest the causative association of these conditions. .

Prevalence, Clinical Features, and Prognosis of Acute Myocardial Infarction Attributable to Coronary Artery Embolism.
Tatsuhiro Shibata, Shoji Kawakami, Teruo Noguchi, Tomotaka Tanaka, Yasuhide Asaumi, Tomoaki Kanaya, Toshiyuki Nagai, Kazuhiro Nakao, Masashi Fujino, Kazuyuki Nagatsuka, Hatsue Ishibashi-Ueda, Kunihiro Nishimura, Yoshihiro Miyamoto, Kengo Kusano, Toshihisa Anzai, Yoichi Goto, Hisao Ogawa, Satoshi Yasuda
Circulation, 132, 4, 241, 50, 28 Jul. 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal

Significance of low plasma levels of brain-derived neurotrophic factor in patients with heart failure.
Seiji Takashio, Seigo Sugiyama, Megumi Yamamuro, Hiroyuki Takahama, Tomohiro Hayashi, Yasuo Sugano, Yasuhiro Izumiya, Seiji Hokimoto, Naoto Minamino, Satoshi Yasuda, Toshihisa Anzai, Hisao Ogawa
The American journal of cardiology, 116, 2, 243, 9, 15 Jul. 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal

Late aneurysm formation of Valsalva sinus after aortic valve replacement due to Takayasu's arteritis.
Akira Funada, Hideaki Kanzaki, Nobutaka Nagano, Yasuo Sugano, Takahiro Ohara, Takuya Hasegawa, Hatsue Ishibashi-Ueda, Masafumi Kitakaze, Toshihisa Anzai
Heart and vessels, 30, 4, 558, 62, Jul. 2015, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Prognostic impact of blood pressure response plus gadolinium enhancement in dilated cardiomyopathy.
Emi Tateishi, Teruo Noguchi, Yoichi Goto, Yoshiaki Morita, Hatsue Ishibashi-Ueda, Naoaki Yamada, Hideaki Kanzaki, Kunihiro Nishimura, Yoshihiro Miyamoto, Toshihisa Anzai, Hisao Ogawa, Satoshi Yasuda
Heart (British Cardiac Society), 101, 10, 774, 80, 15 May 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal

構造的心疾患に対する介入法 経カテーテル大動脈弁置換術の適応患者のスクリーニング法 誰を選択して誰を除外すべきか(Interventions for Structural Heart Disease Optimal Patient Screening for the Transcatheter Aortic Valve Implantation: Who Should and Who Should Not be Selected)　　　　　　　　　　　　　　　
Amaki Makoto, Takashio Seiji, Takahama Hiroyuki, Ohara Takayuki, Hasegawa Takuya, Sugano Yasuo, Kanzaki Hideaki, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 79, Suppl.I, 312, 312, (一社)日本循環器学会, Mar. 2015
English

遺伝的にマルファン症候群と診断された患者における左室機能障害患者の有病率と特徴(Prevalence and Characteristics of the Patients with Left Ventricular Dysfunction in Patients Genetically Diagnosed as Marfan Syndrome)　　　　　　　　　　　　　　　
Yamamoto Yoshiya, Ohhara Takahiro, Funada Akira, Takahama Hiroyuki, Amaki Makoto, Hasegawa Takuya, Sugano Yasuo, Kanzaki Hideaki, Noguchi Teruo, Kusano Kengo, Morisaki Hiroko, Morisaki Takayuki, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 79, Suppl.I, 903, 903, (一社)日本循環器学会, Mar. 2015
English

急性非代償性心不全患者では無症候性甲状腺機能低下症がよくみられ、有害転帰の独立予測因子である(Subclinical Hypothyroidism is Common and an Independent Predictor of Adverse Outcomes in Patients with Acute Decompensated Heart Failure)　　　　　　　　　　　　　　　
Hayashi Tomohiro, Hasegawa Takuya, Kanzaki Hideaki, Funada Akira, Takahama Hiroyuki, Amaki Makoto, Ohhara Takahiro, Sugano Yasuo, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 79, Suppl.I, 1030, 1030, (一社)日本循環器学会, Mar. 2015
English

ヒト血漿中atrial natriuretic peptideの3つの分子型を個別測定する意義(Significance of Individually Measuring Three Molecular Forms of Atrial Natriuretic Peptide in Human Plasma)　　　　　　　　　　　　　　　
Nagai Chiaki, Kangawa Kenji, Takahama Hiroyuki, Takashio Seiji, Hayashi Tomohiro, Anzai Toshihisa, Minamino Naoto
Circulation Journal, 79, Suppl.I, 1209, 1209, (一社)日本循環器学会, Mar. 2015
English

大動脈弁通過血流速度と大動脈弁抵抗が大動脈弁狭窄症の重症度判定に及ぼす影響(Impacts of Transvalvular Flow Rate and Aortic Valve Resistance on Assessment of Severity of Aortic Stenosis)　　　　　　　　　　　　　　　
Kanzaki Hideaki, Funada Akira, Amaki Makoto, Ohhara Takahiro, Takahama Hiroyuki, Hasegawa Takuya, Sugano Yasuo, Kusano Kengo, Kitakaze Masafumi, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 79, Suppl.I, 1340, 1340, (一社)日本循環器学会, Mar. 2015
English

非虚血性拡張型心筋症患者において三尖弁輪収縮期移動距離の変化は運動耐容能の重要な決定因子である(Changes in Tricuspid Annular Plane Systolic Excursion is the Key Determinant of Exercise Capacity in Patients with Non-ischemic Dilated Cardiomyopathy)　　　　　　　　　　　　　　　
Amaki Makoto, Mizuta Rika, Sakamoto Mari, Funada Akira, Takahama Hiroyuki, Ohhara Takahiro, Hasegawa Takuya, Sugano Yasuo, Kanzaki Hideaki, Kitakaze Masafumi, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 79, Suppl.I, 1725, 1725, (一社)日本循環器学会, Mar. 2015
English

広範囲の弁-動脈インピーダンスは駆出率保持にもかかわらず奇異性低流量低圧較差重症大動脈弁狭窄症における左室リモデリングを決定づける(Global Valvulo-Arterial Impedance Determines Left Ventricular Remodeling in Paradoxical Low-Flow, Low-Gradient Severe Aortic Stenosis despite Preserved Ejection Fraction)　　　　　　　　　　　　　　　
Takayama Koichiro, Ohhara Takahiro, Funada Akira, Takahama Hiroyuki, Amaki Makoto, Hasegawa Takuya, Sugano Yasuo, Kanzaki Hideaki, Noguchi Teruo, Kusano Kengo, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 79, Suppl.I, 2211, 2211, (一社)日本循環器学会, Mar. 2015
English

急性非代償性心不全における血漿中の脳由来神経栄養因子の変化(Change of Plasma Brain-derived Neurotrophic Factor Levels in Acute Decompensated Heart Failure)　　　　　　　　　　　　　　　
Takashio Seiji, Takahama Hiroyuki, Hayashi Tomohiro, Minamino Naoto, Sugiyama Seigo, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 79, Suppl.I, 2324, 2324, (一社)日本循環器学会, Mar. 2015
English

CRP値の上昇は閉塞性肥大型心筋症に対する経皮経管的中隔心筋アブレーション後の長期成功と関連している(Elevation of C-reactive Protein Level is Associated with Long-term Success after Percutaneous Transluminal Septal Myocardial Ablation for Hypertrophic Obstructive Cardiomyopathy)　　　　　　　　　　　　　　　
Yasutake Hideki, Sugano Yasuo, Funada Akira, Takahama Hiroyuki, Amaki Makoto, Ohhara Takahiro, Hasegawa Takuya, Kanzaki Hideaki, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 79, Suppl.I, 2426, 2426, (一社)日本循環器学会, Mar. 2015
English

心房細動患者におけるアテローム性動脈硬化症が大動脈ストレインに及ぼす影響(The Effect of Atherosclerosis on Aortic Strain in Patient with Atrial Fibrillation)　　　　　　　　　　　　　　　
Maniwa Naoki, Amaki Makoto, Funada Akira, Takahama Hiroyuki, Ohhara Takahiro, Hasegawa Takuya, Sugano Yasuo, Kanzaki Hideaki, Kitakaze Masafumi, Yasuda Satoshi, Ogawa Hisao, Anzai Toshihisa
Circulation Journal, 79, Suppl.I, 2505, 2505, (一社)日本循環器学会, Mar. 2015
English

慢性心不全および入院歴を有する患者における肺機能の低下(Reduced Pulmonary Function in Patients with Chronic Heart Failure and a History of Admission)　　　　　　　　　　　　　　　
Nakamura Kenji, Kanzaki Hideaki, Funada Akira, Takahama Hiroyuki, Amaki Makoto, Ohhara Takahiro, Hasegawa Takuya, Sugano Yasuo, Asakura Masanori, Noguchi Teruo, Kusano Kengo, Yasuda Satoshi, Ogawa Hisao, Kitakaze Masafumi, Anzai Toshihisa
Circulation Journal, 79, Suppl.I, 2654, 2654, (一社)日本循環器学会, Mar. 2015
English

Efficacy and safety of flecainide for ventricular arrhythmias in patients with Andersen-Tawil syndrome with KCNJ2 mutations.
Koji Miyamoto, Takeshi Aiba, Hiromi Kimura, Hideki Hayashi, Seiko Ohno, Chie Yasuoka, Yoshihito Tanioka, Takeshi Tsuchiya, Yoko Yoshida, Hiroshi Hayashi, Ippei Tsuboi, Ikutaro Nakajima, Kohei Ishibashi, Hideo Okamura, Takashi Noda, Masaharu Ishihara, Toshihisa Anzai, Satoshi Yasuda, Yoshihiro Miyamoto, Shiro Kamakura, Kengo Kusano, Hisao Ogawa, Minoru Horie, Wataru Shimizu
Heart rhythm, 12, 3, 596, 603, Mar. 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal

Role of non-electrocardiogram-gated contrast-enhanced computed tomography in the diagnosis of acute coronary syndrome.
Yoshinori Mano, Toshihisa Anzai, Akihiro Yoshizawa, Yuji Itabashi, Takahiro Ohki
Heart and vessels, 30, 1, 1, 8, Jan. 2015, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Non-contrast T1-weighted magnetic resonance imaging at 3.0 Tesla in a patient undergoing elective percutaneous coronary intervention – clinical and pathological significance of high-intensity plaque.
Yasuhide Asaumi, Teruo Noguchi, Yoshiaki Morita, Taka-Aki Matsuyama, Fumiyuki Otsuka, Reiko Fujiwara, Tomoaki Kanaya, Toshiyuki Nagai, Masahiro Higashi, Kengo Kusano, Toshihisa Anzai, Hatsue Ishibashi-Ueda, Hisao Ogawa, Satoshi Yasuda
Circulation journal : official journal of the Japanese Circulation Society, 79, 1, 218, 20, 2015, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Does major noncardiac surgery accelerate the progression of aortic stenosis? - Role of inflammation.
Makoto Amaki, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 79, 4, 766, 7, 2015, [Peer-reviewed], [Domestic magazines]
English

Risk Stratification of Acute Kidney Injury Using the Blood Urea Nitrogen/Creatinine Ratio in Patients With Acute Decompensated Heart Failure.
Yoichi Takaya, Fumiki Yoshihara, Hiroyuki Yokoyama, Hideaki Kanzaki, Masafumi Kitakaze, Yoichi Goto, Toshihisa Anzai, Satoshi Yasuda, Hisao Ogawa, Yuhei Kawano
Circulation journal : official journal of the Japanese Circulation Society, 79, 7, 1520, 5, 2015, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Effect of Corticosteroid Therapy on Long-Term Clinical Outcome and Left Ventricular Function in Patients With Cardiac Sarcoidosis.
Toshiyuki Nagai, Nobutaka Nagano, Yasuo Sugano, Yasuhide Asaumi, Takeshi Aiba, Hideaki Kanzaki, Kengo Kusano, Teruo Noguchi, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 79, 7, 1593, 600, 2015, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Association Between Basal Thinning of Interventricular Septum and Adverse Long-Term Clinical Outcomes in Patients With Cardiac Sarcoidosis.
Nobutaka Nagano, Toshiyuki Nagai, Yasuo Sugano, Yoshiaki Morita, Yasuhide Asaumi, Takeshi Aiba, Hideaki Kanzaki, Kengo Kusano, Teruo Noguchi, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 79, 7, 1601, 8, 2015, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Clinical and Pathological Impact of Tissue Fibrosis on Lethal Arrhythmic Events in Hypertrophic Cardiomyopathy Patients With Impaired Systolic Function.
Yuko Wada, Takeshi Aiba, Taka-aki Matsuyama, Ikutaro Nakajima, Kohei Ishibashi, Koji Miyamoto, Yuko Yamada, Hideo Okamura, Takashi Noda, Kazuhiro Satomi, Yoshiaki Morita, Hideaki Kanzaki, Kengo Kusano, Toshihisa Anzai, Shiro Kamakura, Hatsue Ishibashi-Ueda, Wataru Shimizu, Minoru Horie, Satoshi Yasuda, Hisao Ogawa
Circulation journal : official journal of the Japanese Circulation Society, 79, 8, 1733, 41, 2015, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Time-Course Changes of Cardiac-Specific Inflammation in a Patient With Left Ventricular Calcified Amorphous Tumor.
Hiroki Yasui, Hiroyuki Takahama, Hideaki Kanzaki, Hatsue Ishibashi-Ueda, Naomi Morita, Yasuo Sugano, Takuya Hasegawa, Takahiro Ohara, Makoto Amaki, Akira Funada, Yasushi Yoshikawa, Satoshi Yasuda, Hisao Ogawa, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 79, 9, 2069, 71, 2015, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Isolated Septal Branch Myocardial Infarction Due to Coronary Spasm Mimicking Non-Ischemic Late Gadolinium Enhancement Pattern on Cardiac Magnetic Resonance Imaging.
Naotsugu Iwakami, Teruo Noguchi, Yoshihiko Ikeda, Emi Tateishi, Yoshiaki Morita, Hideaki Kanzaki, Mitsuhiko Takewa, Toshihisa Anzai, Hisao Ogawa, Satoshi Yasuda
Circulation journal : official journal of the Japanese Circulation Society, 79, 10, 2280, 2, 2015, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Intensity of statin therapy and new hospitalizations for heart failure in patients with type 2 diabetes.
Ichiro Kishimoto, Hisashi Makino, Yoko Ohata, Tamiko Tamanaha, Mayu Tochiya, Toshihisa Anzai, Kengo Kusano, Teruo Noguchi, Satoshi Yasuda, Hisao Ogawa
BMJ open diabetes research & care, 3, 1, e000137, 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal, OBJECTIVE: To examine a relationship between statin intensity and heart failure (HF) incidence in diabetes. RESEARCH DESIGN AND METHODS: We performed a retrospective cohort study of patients with type 2 diabetes (n=600; age, 66.3 years; men, 68%). Patients were categorized into three groups by baseline statin treatments-moderate-intensity, low-intensity, or no statin-and the independent association between the statin category and HF hospitalization during follow-up was examined. RESULTS: Over the course of the median 6-year follow-up, 17.7% of the patients were hospitalized for HF. Cox regression analysis revealed a significant association between the baseline statin category and HF incidence (p=0.002), independently of age, sex, hypertension, B-type natriuretic peptide, glycated hemoglobin, estimated glomerular filtration rate, and low-density lipoprotein (LDL) cholesterol levels. The moderate-intensity statin group had a significantly lower risk for HF than the low-intensity statin group with an adjusted HR of 0.31 (95% CI 0.13 to 0.65, p=0.0014). Interestingly, among patients with prevalent coronary artery diseases (CAD) and with baseline LDL controlled to less than 100 mg/dL, the frequency of HF was still significantly lower in the moderate-intensity group than in the low-intensity group or the no statin group. The effect of baseline statin category on HF was independent of incident CAD events during follow-up. CONCLUSIONS: In type 2 diabetes, moderate-intensity statins, in comparison to low-intensity or no statin, were associated with lower HF incidence independently of LDL levels or of CAD events.

Impact of acute and chronic hyperglycemia on in-hospital outcomes of patients with acute myocardial infarction.
Masashi Fujino, Masaharu Ishihara, Satoshi Honda, Shoji Kawakami, Takafumi Yamane, Toshiyuki Nagai, Kazuhiro Nakao, Tomoaki Kanaya, Leon Kumasaka, Yasuhide Asaumi, Tetsuo Arakawa, Yoshio Tahara, Michio Nakanishi, Teruo Noguchi, Kengo Kusano, Toshihisa Anzai, Yoichi Goto, Satoshi Yasuda, Hisao Ogawa
The American journal of cardiology, 114, 12, 1789, 93, 15 Dec. 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

Pathophysiological impact of serum fibroblast growth factor 23 in patients with nonischemic cardiac disease and early chronic kidney disease.
Miki Imazu, Hiroyuki Takahama, Hiroshi Asanuma, Akira Funada, Yasuo Sugano, Takahiro Ohara, Takuya Hasegawa, Masanori Asakura, Hideaki Kanzaki, Toshihisa Anzai, Masafumi Kitakaze
American journal of physiology. Heart and circulatory physiology, 307, 10, H1504-11, H1511, 15 Nov. 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

Trends in the clinical and pathological characteristics of cardiac rupture in patients with acute myocardial infarction over 35 years.
Satoshi Honda, Yasuhide Asaumi, Takafumi Yamane, Toshiyuki Nagai, Tadayoshi Miyagi, Teruo Noguchi, Toshihisa Anzai, Yoichi Goto, Masaharu Ishihara, Kunihiro Nishimura, Hisao Ogawa, Hatsue Ishibashi-Ueda, Satoshi Yasuda
Journal of the American Heart Association, 3, 5, e000984, 20 Oct. 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

Incidence and prognostic significance of myocardial late gadolinium enhancement in patients with sarcoidosis without cardiac manifestation.
Toshiyuki Nagai, Shun Kohsaka, Shigeo Okuda, Toshihisa Anzai, Koichiro Asano, Keiichi Fukuda
Chest, 146, 4, 1064, 1072, Oct. 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

Development of a web system to support the management of chronic heart failure patients for use in disaster-stricken areas
Shoko Tani, Yoshihiro Miyamoto, Toshihisa Anzai, Shigeki Kuwata, Takeshi Kuwahara, Yasuo Sugano, Toshinari Nakao, Kiyokazu Kawakami, Naoko Ueno, Hiroshi Inada, Kazuo Nakazawa
Transactions of Japanese Society for Medical and Biological Engineering, 52, 259, O-260, Japan Soc. of Med. Electronics and Biol. Engineering, 17 Aug. 2014, [Peer-reviewed]
Japanese, Scientific journal

Extensive late gadolinium enhancement on cardiovascular magnetic resonance predicts adverse outcomes and lack of improvement in LV function after steroid therapy in cardiac sarcoidosis.
Takayuki Ise, Takuya Hasegawa, Yoshiaki Morita, Naoaki Yamada, Akira Funada, Hiroyuki Takahama, Makoto Amaki, Hideaki Kanzaki, Hideo Okamura, Shiro Kamakura, Wataru Shimizu, Toshihisa Anzai, Masafumi Kitakaze
Heart (British Cardiac Society), 100, 15, 1165, 72, Aug. 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

Decreased myocardial dendritic cells is associated with impaired reparative fibrosis and development of cardiac rupture after myocardial infarction in humans.
Toshiyuki Nagai, Satoshi Honda, Yasuo Sugano, Taka-aki Matsuyama, Keiko Ohta-Ogo, Yasuhide Asaumi, Yoshihiko Ikeda, Kengo Kusano, Masaharu Ishihara, Satoshi Yasuda, Hisao Ogawa, Hatsue Ishibashi-Ueda, Toshihisa Anzai
Journal of the American Heart Association, 3, 3, e000839, 03 Jun. 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

Hemoglobin A1c predicts heart failure hospitalization independent of baseline cardiac function or B-type natriuretic peptide level.
Ichiro Kishimoto, Hisashi Makino, Yoko Ohata, Tamiko Tamanaha, Mayu Tochiya, Akiko Kada, Masaharu Ishihara, Toshihisa Anzai, Wataru Shimizu, Satoshi Yasuda, Hisao Ogawa
Diabetes research and clinical practice, 104, 2, 257, 65, May 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

非虚血性/虚血性心筋症患者における間葉系幹細胞移植の長期予後への影響と安全性(The Long-term Prognostic Impact and Safety of Mesenchymal Stem Cells Transplantation in Patients with Non-ischemic/Ischemic Cardiomyopathy)　　　　　　　　　　　　　　　
Yagyu Takeshi, Asaumi Yasuhide, Takahama Hiroyuki, Noguchi Teruo, Nagaya Noritoshi, Anzai Toshihisa, Kusano Kengo, Ishihara Masaharu, Kitakaze Masafumi, Ogawa Hisao, Kangawa Kenji, Yasuda Satoshi
Circulation Journal, 78, Suppl.I, 61, 61, (一社)日本循環器学会, Mar. 2014
English

Admission hyperglycemia is an independent predictor of acute kidney injury in patients with acute myocardial infarction.
Noriaki Moriyama, Masaharu Ishihara, Teruo Noguchi, Michio Nakanishi, Tetsuo Arakawa, Yasuhide Asaumi, Leon Kumasaka, Tomoaki Kanaya, Tadayoshi Miyagi, Toshiyuki Nagai, Takafumi Yamane, Masashi Fujino, Satoshi Honda, Reiko Fujiwara, Toshihisa Anzai, Kengo Kusano, Yoichi Goto, Satoshi Yasuda, Hisao Ogawa
Circulation journal : official journal of the Japanese Circulation Society, 78, 6, 1475, 80, 2014, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Massive mobile thrombus in the left ventricle due to Löffler endocarditis complicated with dilated cardiomyopathy.
Takahiro Nakashima, Akira Funada, Hideaki Kanzaki, Yasuo Sugano, Takahiro Ohara, Takuya Hasegawa, Hatsue Ishibashi-Ueda, Masafumi Kitakaze, Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 78, 8, 1992, 4, 2014, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Electrocardiographic predictors of response to cardiac resynchronization therapy in patients with intraventricular conduction delay.
Yoichi Takaya, Takashi Noda, Ikutaro Nakajima, Yuko Yamada, Koji Miyamoto, Hideo Okamura, Kazuhiro Satomi, Takeshi Aiba, Kengo F Kusano, Hideaki Kanzaki, Toshihisa Anzai, Masaharu Ishihara, Satoshi Yasuda, Hisao Ogawa, Shiro Kamakura, Wataru Shimizu
Circulation journal : official journal of the Japanese Circulation Society, 78, 1, 71, 7, 2014, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Significance of AT1 receptor independent activation of mineralocorticoid receptor in murine diabetic cardiomyopathy.
Yuji Nagatomo, Tomomi Meguro, Hiroyuki Ito, Kimi Koide, Toshihisa Anzai, Keiichi Fukuda, Satoshi Ogawa, Tsutomu Yoshikawa
PloS one, 9, 3, e93145, 2014, [Peer-reviewed], [International Magazine]
English, Scientific journal

Left circumflex coronary artery is protected against no-reflow phenomenon following percutaneous coronary intervention for coronary artery disease.
Toshiyuki Nagai, Takuro Hirano, Mayumi Tsunoda, Haruhiko Hosaka, Yoshikazu Kishino, Takaharu Katayama, Keisuke Matsumura, Takashi Miyagawa, Shun Kohsaka, Toshihisa Anzai, Keiichi Fukuda, Masahiro Suzuki
Heart and vessels, 28, 5, 559, 65, Sep. 2013, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Eicosapentaenoic acid suppresses adverse effects of C-reactive protein overexpression on pressure overload-induced cardiac remodeling.
Toshiyuki Nagai, Toshihisa Anzai, Yoshinori Mano, Hidehiro Kaneko, Atsushi Anzai, Yasuo Sugano, Yuichiro Maekawa, Toshiyuki Takahashi, Tsutomu Yoshikawa, Keiichi Fukuda
Heart and vessels, 28, 3, 404, 11, May 2013, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

心不全患者の根本原因の評価における心血管MRと心内膜心筋生検との直接比較(Head-to-Head Comparison between Cardiovascular Magnetic Resonance and Endomyocardial Biopsy for Evaluating Underlying Etiology in Patients with Heart Failure)　　　　　　　　　　　　　　　
Yoshida Akemi, Ishibashi-Ueda Hatsue, Yamada Naoaki, Kanzaki Hideaki, Hasegawa Takuya, Ohhara Takahiro, Takahama Hiroyuki, Amaki Makoto, Funada Akira, Asakura Masanori, Anzai Toshihisa, Kitakaze Masafumi
Circulation Journal, 77, Suppl.I, 42, 42, (一社)日本循環器学会, Mar. 2013
English

Post-infarction inflammation and left ventricular remodeling: a double-edged sword.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 77, 3, 580, 7, 2013, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, After myocardial infarction (MI), inflammatory cells such as neutrophils, followed by monocytes and macrophages, infiltrate and phagocytose the necrotic tissues, as well as secreting a variety of inflammatory cytokines. The vulnerable myocardium, which consists of necrotic tissue and inflammatory cells, is susceptible to wall stress, resulting in infarct expansion. Subacute cardiac rupture is an extreme form of infarct expansion, whereas ventricular aneurysm is its chronic form and a trigger for subsequent left ventricular (LV) remodeling. Although post-infarction inflammation is essential for the healing process, excessive inflammation could play an important role in the development of LV remodeling. Increase in the C-reactive protein level, which reflects myocardial inflammation, is reported to be a useful predictive marker for cardiac rupture, ventricular aneurysm and LV remodeling. In addition, an increase in peripheral monocyte count is associated with a poor outcome after MI, and an animal study has demonstrated that granulocyte/macrophage-colony stimulating factor induction causes excessive macrophage infiltration in the infarcted area and worsening of LV remodeling. Recently, it was also found that dendritic cells play an important role in controlling excessive inflammation caused by monocytes/macrophages. Thus, inflammation that develops after MI is a double-edged sword, and how to control inflammation to suppress pathological remodeling is an important issue to be considered in developing new treatment for heart failure.

Extent of heart rate reduction during hospitalization using beta-blockers, not the achieved heart rate itself at discharge, predicts the clinical outcome in patients with acute heart failure syndromes.
Hiroyuki Takahama, Hiroyuki Yokoyama, Akiko Kada, Kenichi Sekiguchi, Masashi Fujino, Akira Funada, Makoto Amaki, Takuya Hasegawa, Masanori Asakura, Hideaki Kanzaki, Toshihisa Anzai, Masafumi Kitakaze
Journal of cardiology, 61, 1, 58, 64, Jan. 2013, [Peer-reviewed], [International Magazine]
English, Scientific journal, AIM: It has been uncertain whether patients with acute heart failure syndromes (AHFSs) benefit from a lower heart rate (HR) itself or from treatment for heart failure (HF) that reduces sympathetic tone with consequent HR reduction (HRR). The present study investigated the influence of HRR during hospitalization on the prognosis of AHFS patients. METHODS AND RESULTS: In 421 AHFS patients, we analyzed the relationship between HRR during hospitalization and the prognosis after discharge. During a mean follow-up period of 1.9 years, 76 and 55 patients died or were re-hospitalized for HF, respectively. Although HR at discharge did not influence cardiac events (hazard ratio [HR]: 1.00 [95% CI; 0.99-1.02], p=0.22), the extent of HRR was a predictor of cardiac events (HR: 0.89 [0.84-0.96], p<0.001). Kaplan-Meier analysis revealed that the cardiac event rate of the HRR-positive group (≥ 27 bpm reduction of HR from 114 ± 24 at admission to 65 ± 11 bpm at discharge) was significantly lower than that of the HRR-negative group (≤ 26 bpm (=median value) reduction of HR from 74 ± 14 to 71 ± 14 bpm). In the HRR-positive group, the cardiac event rate was significantly lower in patients receiving beta-blockers. Furthermore, the extent of HR change was an important predictor of cardiac events among other markers, compared with the change in systolic blood pressure or B-type natriuretic peptide. CONCLUSION: The HR itself at discharge was not associated with the prognosis, but the extent of HRR achieved by treatment of HF with beta-blockers was a strong predictor for the clinical outcome in AHFS patients.

Post-infarction inflammation and left ventricular remodeling: a double-edged sword.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 77, 3, 580, 7, 2013, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Titration of β-blockers for patients with heart failure.
Toshihisa Anzai
Circulation journal : official journal of the Japanese Circulation Society, 77, 4, 902, 3, 2013, [Peer-reviewed], [Domestic magazines]
English

A successful case of percutaneous transluminal septal myocardial ablation for mitral regurgitation that emerged following mitral valve repair surgery.
Tomohiro Hayashi, Makoto Amaki, Hideaki Kanzaki, Akira Funada, Yasuo Sugano, Takahiro Ohara, Hiroyuki Takahama, Takuya Hasegawa, Masafumi Kitakaze, Toshihisa Anzai
Internal medicine (Tokyo, Japan), 52, 24, 2765, 9, 2013, [Peer-reviewed], [Domestic magazines]
English, Scientific journal, A 70-year-old man complaining of exertional dyspnea was referred to our hospital for recurrence of mitral regurgitation (MR) after mitral valve repair. Echocardiography revealed the presence of a bulging subaortic septum with flow acceleration in the left ventricular outflow tract (LVOT) and systolic anterior motion of the mitral valve with moderate MR, consistent with LVOT obstruction. Since medical therapy was not sufficiently effective, we performed percutaneous transluminal septal myocardial ablation (PTSMA). After the procedure, the MR resolved, with a reduced LVOT pressure gradient. The patient's symptoms improved. PTSMA was effective for the treatment of MR that emerged after mitral valve repair.

Eosinophilia associated with dobutamine allergy causes eosinophilic endomyocarditis confirmed by serial endomyocardial biopsies.
Moritoshi Funasako, Akira Funada, Hideaki Kanzaki, Hiroyuki Takahama, Makoto Amaki, Takuya Hasegawa, Yoshihiko Ikeda, Hatsue Ishibashi-Ueda, Toshihisa Anzai, Masafumi Kitakaze
Journal of cardiology cases, 6, 6, e179-e182, e182, Dec. 2012, [Peer-reviewed], [Domestic magazines]
English, We report a case of eosinophilic endomyocarditis caused by eosinophilia due to dobutamine allergy and successfully treated by a short-term and medium-dose steroid administration. Serial endomyocardial biopsies were useful for early diagnosis and evaluation of the effect of the treatment. Eosinophilic endomyocarditis due to dobutamine allergy is a rare entity; however, because of the high utilization rate of dobutamine in patients with low output heart failure, it is important to recognize that additional deterioration of cardiac function caused by eosinophilic endomyocarditis makes prognosis poor and early intervention is necessary. .

High-mobility group box 1 protein blockade suppresses development of abdominal aortic aneurysm.
Takashi Kohno, Toshihisa Anzai, Hidehiro Kaneko, Yasuo Sugano, Hideyuki Shimizu, Masayuki Shimoda, Taku Miyasho, Minoru Okamoto, Hiroshi Yokota, Shingo Yamada, Tsutomu Yoshikawa, Yasunori Okada, Ryohei Yozu, Satoshi Ogawa, Keiichi Fukuda
Journal of cardiology, 59, 3, 299, 306, May 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

Effect of preoperative evaluation by multidetector computed tomography in percutaneous coronary interventions of chronic total occlusions.
Koji Ueno, Akio Kawamura, Takeshi Onizuka, Takashi Kawakami, Yuji Nagatomo, Kentaro Hayashida, Shinsuke Yuasa, Yuichiro Maekawa, Toshihisa Anzai, Masahiro Jinzaki, Sachio Kuribayashi, Satoshi Ogawa
International journal of cardiology, 156, 1, 76, 9, 05 Apr. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

Regulatory role of dendritic cells in postinfarction healing and left ventricular remodeling.
Atsushi Anzai, Toshihisa Anzai, Shigenori Nagai, Yuichiro Maekawa, Kotaro Naito, Hidehiro Kaneko, Yasuo Sugano, Toshiyuki Takahashi, Hitoshi Abe, Satsuki Mochizuki, Motoaki Sano, Tsutomu Yoshikawa, Yasunori Okada, Shigeo Koyasu, Satoshi Ogawa, Keiichi Fukuda
Circulation, 125, 10, 1234, 45, 13 Mar. 2012, [Peer-reviewed], [International Magazine]
English, Scientific journal

Low incidence of catheter-related complications in patients with advanced pulmonary arterial hypertension undergoing continuous epoprostenol infusion.
Toshiyuki Nagai, Shun Kohsaka, Toshihisa Anzai, Tsutomu Yoshikawa, Keiichi Fukuda, Toru Sato
Chest, 141, 1, 272, 273, Jan. 2012, [Peer-reviewed], [International Magazine]
English

Significance of electrocardiographic right ventricular hypertrophy in patients with pulmonary hypertension with or without right ventricular systolic dysfunction.
Toshiyuki Nagai, Shun Kohsaka, Mitsushige Murata, Shigeo Okuda, Toshihisa Anzai, Keiichi Fukuda, Toru Satoh
Internal medicine (Tokyo, Japan), 51, 17, 2277, 83, 2012, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Dendritic Cell is an Immunoprotective Regulator in Post-Infarction Healing and Left Ventricular Remodeling
Atsushi Anzai, Toshihisa Anzai, Shigenori Nagai, Yuichiro Maekawa, Motoaki Sano, Tsutomu Yoshikawa, Shigeo Koyasu, Satoshi Ogawa, Keiichi Fukuda
CIRCULATION, 124, 21, Nov. 2011, [Peer-reviewed]
English

[Ivabradine (pure heart-rate-lowering agent)].
Toshihisa Anzai
Nihon rinsho. Japanese journal of clinical medicine, 69 Suppl 9, 412, 6, Nov. 2011, [Peer-reviewed], [Domestic magazines]
Japanese, Scientific journal

Tumor necrosis factor-α converting enzyme is a key mediator of abdominal aortic aneurysm development.
Hidehiro Kaneko, Toshihisa Anzai, Keisuke Horiuchi, Takashi Kohno, Toshiyuki Nagai, Atsushi Anzai, Toshiyuki Takahashi, Aya Sasaki, Masayuki Shimoda, Yuichiro Maekawa, Hideyuki Shimizu, Tsutomu Yoshikawa, Yasunori Okada, Ryohei Yozu, Keiichi Fukuda
Atherosclerosis, 218, 2, 470, 8, Oct. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

[Beta-blocker].
Toshihisa Anzai
Nihon rinsho. Japanese journal of clinical medicine, 69 Suppl 7, 445, 9, Sep. 2011, [Peer-reviewed], [Domestic magazines]
Japanese, Scientific journal

Human C-reactive protein exacerbates metabolic disorders in association with adipose tissue remodelling.
Hidehiro Kaneko, Toshihisa Anzai, Toshiyuki Nagai, Atsushi Anzai, Toshiyuki Takahashi, Yoshinori Mano, Kohkichi Morimoto, Yuichiro Maekawa, Hiroshi Itoh, Tsutomu Yoshikawa, Satoshi Ogawa, Keiichi Fukuda
Cardiovascular research, 91, 3, 546, 55, 01 Aug. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Resveratrol prevents the development of abdominal aortic aneurysm through attenuation of inflammation, oxidative stress, and neovascularization.
Hidehiro Kaneko, Toshihisa Anzai, Maho Morisawa, Takashi Kohno, Toshiyuki Nagai, Atsushi Anzai, Toshiyuki Takahashi, Masayuki Shimoda, Aya Sasaki, Yuichiro Maekawa, Koichi Yoshimura, Hiroki Aoki, Kazuo Tsubota, Tsutomu Yoshikawa, Yasunori Okada, Satoshi Ogawa, Keiichi Fukuda
Atherosclerosis, 217, 2, 350, 7, Aug. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Role of vascular endothelial growth factor-A in development of abdominal aortic aneurysm.
Hidehiro Kaneko, Toshihisa Anzai, Toshiyuki Takahashi, Takashi Kohno, Masayuki Shimoda, Aya Sasaki, Hideyuki Shimizu, Toshiyuki Nagai, Yuichiro Maekawa, Koichi Yoshimura, Hiroki Aoki, Tsutomu Yoshikawa, Yasunori Okada, Ryohei Yozu, Satoshi Ogawa, Keiichi Fukuda
Cardiovascular research, 91, 2, 358, 67, 15 Jul. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Impact of serum high-mobility group box 1 protein elevation on oxygenation impairment after thoracic aortic aneurysm repair.
Takashi Kohno, Toshihisa Anzai, Hideyuki Shimizu, Hidehiro Kaneko, Yasuo Sugano, Shingo Yamada, Tsutomu Yoshikawa, Akitoshi Ishizaka, Ryohei Yozu, Satoshi Ogawa
Heart and vessels, 26, 3, 306, 12, May 2011, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Can intravascular ultrasound guidance modify the efficacy of drug-eluting stent over bare-metal stent in an aorto-ostial lesion?
Teruo Okabe, Akio Kawamura, Yuichiro Maekawa, Toshihisa Anzai, Shiro Iwanaga, Tsutomu Yoshikawa, Satoshi Ogawa
Cardiovascular Revascularization Medicine, 12, 2, 105, 110, Mar. 2011, [Peer-reviewed]
English, Scientific journal

C-reactive protein overexpression exacerbates pressure overload-induced cardiac remodeling through enhanced inflammatory response.
Toshiyuki Nagai, Toshihisa Anzai, Hidehiro Kaneko, Yoshinori Mano, Atsushi Anzai, Yuichiro Maekawa, Toshiyuki Takahashi, Tomomi Meguro, Tsutomu Yoshikawa, Keiichi Fukuda
Hypertension (Dallas, Tex. : 1979), 57, 2, 208, 15, Feb. 2011, [Peer-reviewed], [International Magazine]
English, Scientific journal

Overexpression of human C-reactive protein exacerbates left ventricular remodeling in diabetic cardiomyopathy.
Yoshinori Mano, Toshihisa Anzai, Hidehiro Kaneko, Yuji Nagatomo, Toshiyuki Nagai, Atsushi Anzai, Yuichiro Maekawa, Toshiyuki Takahashi, Tomomi Meguro, Tsutomu Yoshikawa, Keiichi Fukuda
Circulation journal : official journal of the Japanese Circulation Society, 75, 7, 1717, 27, 2011, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Tumor necrosis factor-α converting enzyme inactivation ameliorates high-fat diet-induced insulin resistance and altered energy homeostasis.
Hidehiro Kaneko, Toshihisa Anzai, Keisuke Horiuchi, Kokichi Morimoto, Atsushi Anzai, Toshiyuki Nagai, Yasuo Sugano, Yuichiro Maekawa, Hiroshi Itoh, Tsutomu Yoshikawa, Yasunori Okada, Satoshi Ogawa, Keiichi Fukuda
Circulation journal : official journal of the Japanese Circulation Society, 75, 10, 2482, 90, 2011, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Increased C-reactive protein expression exacerbates left ventricular dysfunction and remodeling after myocardial infarction.
Toshiyuki Takahashi, Toshihisa Anzai, Hidehiro Kaneko, Yoshinori Mano, Atsushi Anzai, Toshiyuki Nagai, Takashi Kohno, Yuichiro Maekawa, Tsutomu Yoshikawa, Keiichi Fukuda, Satoshi Ogawa
American journal of physiology. Heart and circulatory physiology, 299, 6, H1795-804, H1804, Dec. 2010, [Peer-reviewed], [International Magazine]
English, Scientific journal

Re-elevation of D-dimer as a predictor of re-dissection and venous thromboembolism after Stanford type B acute aortic dissection.
Yusuke Jo, Toshihisa Anzai, Koji Ueno, Hidehiro Kaneko, Takashi Kohno, Yasuo Sugano, Yuichiro Maekawa, Tsutomu Yoshikawa, Hideyuki Shimizu, Ryohei Yozu, Satoshi Ogawa
Heart and vessels, 25, 6, 509, 14, Nov. 2010, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Impact of systemic acidosis on the development of malignant ventricular arrhythmias after reperfusion therapy for ST-elevation myocardial infarction.
Toshiyuki Nagai, Toshihisa Anzai, Hidehiro Kaneko, Atsushi Anzai, Yoshinori Mano, Yuji Nagatomo, Shun Kohsaka, Yuichiro Maekawa, Akio Kawamura, Tsutomu Yoshikawa, Satoshi Ogawa
Circulation journal : official journal of the Japanese Circulation Society, 74, 9, 1808, 14, Sep. 2010, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Differential effects of carvedilol and metoprolol on renal function in patients with heart failure.
Hiroyuki Ito, Yuji Nagatomo, Takashi Kohno, Toshihisa Anzai, Tomomi Meguro, Satoshi Ogawa, Tsutomu Yoshikawa
Circulation journal : official journal of the Japanese Circulation Society, 74, 8, 1578, 83, Aug. 2010, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Prognostic significance of acute kidney injury after reperfused ST-elevation myocardial infarction: synergistic acceleration of renal dysfunction and left ventricular remodeling.
Atsushi Anzai, Toshihisa Anzai, Kotaro Naito, Hidehiro Kaneko, Yoshinori Mano, Yusuke Jo, Yuji Nagatomo, Yuichiro Maekawa, Akio Kawamura, Tsutomu Yoshikawa, Satoshi Ogawa
Journal of cardiac failure, 16, 5, 381, 9, May 2010, [Peer-reviewed], [International Magazine]
English, Scientific journal

Elevated troponin T on discharge predicts poor outcome of decompensated heart failure.
Kimi Koide, Tsutomu Yoshikawa, Yuji Nagatomo, Shun Kohsaka, Toshihisa Anzai, Tomomi Meguro, Satoshi Ogawa
Heart and vessels, 25, 3, 217, 22, May 2010, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Impact of high-density lipoprotein cholesterol level in patients with variant angina pectoris.
Yasuo Sugano, Toshihisa Anzai, Takashi Yagi, Shigetaka Noma
International journal of cardiology, 140, 2, 175, 81, 15 Apr. 2010, [Peer-reviewed], [International Magazine]
English, Scientific journal

Persistent Angiotensin II Independent Activation of Mineralocorticoid Receptor Signaling is Associated With the Deterioration of Cardiac Function Induced by Chronic Diabetes Mellitus
Yuji Nagatomo, Tomomi Meguro, Hiroyuki Ito, Kimi Koide, Toshihisa Anzai, Satoshi Ogawa, Tsutomu Yoshikawa
CIRCULATION, 120, 18, S782, S782, Nov. 2009, [Peer-reviewed]
English

Role of ischemic preconditioning and inflammatory response in the development of malignant ventricular arrhythmias after reperfused ST-elevation myocardial infarction.
Hidehiro Kaneko, Toshihisa Anzai, Kotaro Naito, Takashi Kohno, Yuichiro Maekawa, Toshiyuki Takahashi, Akio Kawamura, Tsutomu Yoshikawa, Satoshi Ogawa
Journal of cardiac failure, 15, 9, 775, 81, Nov. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Increased epicardial fat volume quantified by 64-multidetector computed tomography is associated with coronary atherosclerosis and totally occlusive lesions.
Koji Ueno, Toshihisa Anzai, Masahiro Jinzaki, Minoru Yamada, Yusuke Jo, Yuichiro Maekawa, Akio Kawamura, Tsutomu Yoshikawa, Yutaka Tanami, Kozo Sato, Sachio Kuribayashi, Satoshi Ogawa
Circulation journal : official journal of the Japanese Circulation Society, 73, 10, 1927, 33, Oct. 2009, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Increased epicardial fat volume quantified by 64-multidetector computed tomography is associated with coronary atherosclerosis and totally occlusive lesions.
Koji Ueno, Toshihisa Anzai, Masahiro Jinzaki, Minoru Yamada, Yusuke Jo, Yuichiro Maekawa, Akio Kawamura, Tsutomu Yoshikawa, Yutaka Tanami, Kozo Sato, Sachio Kuribayashi, Satoshi Ogawa
Circulation journal : official journal of the Japanese Circulation Society, 73, 10, 1927, 33, Oct. 2009, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Differential Effects of Carvedilol and Metoprolol on Renal Function in Patients With Heart Failure
Hiroyuki Ito, Yuji Nagatomo, Takashi Kohno, Toshihisa Anzai, Tomomi Meguro, Satoshi Ogawa, Tsutomu Yoshikawa
JOURNAL OF CARDIAC FAILURE, 15, 7, S160, S160, Sep. 2009, [Peer-reviewed]
English

Persistent Angiotensin II-independent Activation of Mineralocorticoid Receptor Signaling is Associated With the Cardiac Dysfunction Induced by Long-term Diabetes Mellitus
Yuji Nagatomo, Tomomi Meguro, Hiroyuki Ito, Kimi Koide, Toshihisa Anzai, Satoshi Ogawa, Tsutomu Yoshikawa
JOURNAL OF CARDIAC FAILURE, 15, 7, S168, S169, Sep. 2009, [Peer-reviewed]
English

Diagnostic Accuracy of Angiographic View Image for the Detection of Coronary Artery Stenoses by 64-Detector Row CT - A Pilot Study Comparison With Conventional Post-Processing Methods and Axial Images Alone
Masahiro Jinzaki, Kozo Sato, Yutaka Tanami, Minoru Yamada, Toshihisa Anzai, Akio Kawamura, Koji Ueno, Sachio Kuribayashi
CIRCULATION JOURNAL, 73, 4, 691, 698, Apr. 2009, [Peer-reviewed]
English, Scientific journal

Diagnostic accuracy of angiographic view image for the detection of coronary artery stenoses by 64-detector row CT: a pilot study comparison with conventional post-processing methods and axial images alone.
Masahiro Jinzaki, Kozo Sato, Yutaka Tanami, Minoru Yamada, Toshihisa Anzai, Akio Kawamura, Koji Ueno, Sachio Kuribayashi
Circulation journal : official journal of the Japanese Circulation Society, 73, 4, 691, 8, Apr. 2009, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

A pilot study on the role of autoantibody targeting the beta1-adrenergic receptor in the response to beta-blocker therapy for congestive heart failure.
Yuji Nagatomo, Tsutomu Yoshikawa, Takashi Kohno, Akihiro Yoshizawa, Akiyasu Baba, Toshihisa Anzai, Tomomi Meguro, Toru Satoh, Satoshi Ogawa
Journal of cardiac failure, 15, 3, 224, 32, Apr. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Role of high-mobility group box 1 protein in post-infarction healing process and left ventricular remodelling.
Takashi Kohno, Toshihisa Anzai, Kotaro Naito, Taku Miyasho, Minoru Okamoto, Hiroshi Yokota, Shingo Yamada, Yuichiro Maekawa, Toshiyuki Takahashi, Tsutomu Yoshikawa, Akitoshi Ishizaka, Satoshi Ogawa
Cardiovascular research, 81, 3, 565, 73, 15 Feb. 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Diagnostic capacity of 64-slice multidetector computed tomography for acute coronary syndrome in patients presenting with acute chest pain.
Koji Ueno, Toshihisa Anzai, Masahiro Jinzaki, Minoru Yamada, Takashi Kohno, Akio Kawamura, Tsutomu Yoshikawa, Sachio Kuribayashi, Satoshi Ogawa
Cardiology, 112, 3, 211, 8, 2009, [Peer-reviewed], [International Magazine]
English, Scientific journal

Extrinsic compression of the left main coronary artery by atrial septal defect.
Yusuke Jo, Akio Kawamura, Masahiro Jinzaki, Takashi Kohno, Toshihisa Anzai, Shiro Iwanaga, Kiyokazu Kokaji, Tsutomu Yoshikawa, Ryohei Yozu, Sachio Kuribayashi, Satoshi Ogawa
The Annals of thoracic surgery, 86, 6, 1987, 9, Dec. 2008, [Peer-reviewed], [International Magazine]
English, Scientific journal

Impact of chronic kidney disease on postinfarction inflammation, oxidative stress, and left ventricular remodeling.
Kotaro Naito, Toshihisa Anzai, Tsutomu Yoshikawa, Atsushi Anzai, Hidehiro Kaneko, Takashi Kohno, Toshiyuki Takahashi, Akio Kawamura, Satoshi Ogawa
Journal of cardiac failure, 14, 10, 831, 8, Dec. 2008, [Peer-reviewed], [International Magazine]
English, Scientific journal

Differential effects of GM-CSF and G-CSF on infiltration of dendritic cells during early left ventricular remodeling after myocardial infarction.
Kotaro Naito, Toshihisa Anzai, Yasuo Sugano, Yuichiro Maekawa, Takashi Kohno, Tsutomu Yoshikawa, Kenjiro Matsuno, Satoshi Ogawa
Journal of immunology (Baltimore, Md. : 1950), 181, 8, 5691, 701, 15 Oct. 2008, [Peer-reviewed], [International Magazine]
English, Scientific journal

Angiotensin-receptor blockade reduces border zone myocardial monocyte chemoattractant protein-1 expression and macrophage infiltration in post-infarction ventricular remodeling.
Takashi Kohno, Toshihisa Anzai, Kotaro Naito, Yasuo Sugano, Yuichiro Maekawa, Toshiyuki Takahashi, Tsutomu Yoshikawa, Satoshi Ogawa
Circulation journal : official journal of the Japanese Circulation Society, 72, 10, 1685, 92, Oct. 2008, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Angiotensin-receptor blockade reduces border zone myocardial monocyte chemoattractant protein-1 expression and macrophage infiltration in post-infarction ventricular remodeling
Takashi Kohno, Toshihisa Anzai, Kotaro Naito, Yasuo Sugano, Yuichiro Maekawa, Toshiyuki Takahashi, Tsutomu Yoshikawa, Satoshi Ogawa
CIRCULATION JOURNAL, 72, 10, 1685, 1692, Oct. 2008, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Angiotensin II independent mineralocorticoid receptor activation in heart failure models
Tomomi Meguro, Yuji Nagato, Kimi Koide, Hiroyuki Ito, Toshihisa Anzai, Satoshi Ogawa, Tsutomu Yoshikawa
JOURNAL OF CARDIAC FAILURE, 14, 7, S147, S147, Sep. 2008, [Peer-reviewed]
English

Effect of human C-reactive protein on cardiac function and angiotensin 2 signaling in diabetic cardiomyopathy
Yoshinori Mano, Toshihisa Anzai, Toshiyuki Takahashi, Yuji Nagatomo, Kimi Koide, Hidehiro Kaneko, Tomomi Meguro, Tsutomu Yoshikawa, Satoshi Ogawa
JOURNAL OF CARDIAC FAILURE, 14, 7, S170, S170, Sep. 2008, [Peer-reviewed]
English

Persistent elevation in troponin T level during convalescence is associated with inflammatory response in patients with decompensated heart failure
Kimi Koide, Tsutomu Yoshikawa, Yuji Nagatomo, Toshihisa Anzai, Tomomi Meguro, Satoshi Ogawa
JOURNAL OF CARDIAC FAILURE, 14, 7, S171, S171, Sep. 2008, [Peer-reviewed]
English

Use of renin-angiotensin inhibitors at discharge in patients hospitalized for heart failure is associated with improved survival
Yusuke Yoshimatsu, Shun Kohsaka, Kimi Koide, Yuji Nagatomo, Hiroyuki Ito, Tomomi Meguro, Toshihisa Anzai, Satoshi Ogawa, Tsutomu Yoshikawa
JOURNAL OF CARDIAC FAILURE, 14, 7, S173, S173, Sep. 2008, [Peer-reviewed]
English

Impact of optimal medical therapy at discharge in patients with heart failure: Characteristics and long-term outcome
Shuhei Ito, Shun Kohsaka, Kipvii Koide, Yuji Nagatomo, Hiroyuki Ito, Tomomi Meguro, Toshihisa Anzai, Satoshi Ogawa, Tsutomu Yoshikaa
JOURNAL OF CARDIAC FAILURE, 14, 7, S173, S173, Sep. 2008, [Peer-reviewed]
English

Differential effects of carvedilol and metoprolol on renal function in patients with heart failure
Hiroyuki Ito, Yuji Nagatomo, Takashi Kohno, Toshihisa Anzai, Tomomi Meguro, Satoshi Ogawa, Tsutomu Ycshikawa
JOURNAL OF CARDIAC FAILURE, 14, 7, S174, S174, Sep. 2008, [Peer-reviewed]
English

Early use of beta-blockers attenuates systemic inflammatory response and lung oxygenation impairment after distal type acute aortic dissection.
Yusuke Jo, Toshihisa Anzai, Yasuo Sugano, Kotaro Naito, Koji Ueno, Takashi Kohno, Tsutomu Yoshikawa, Satoshi Ogawa
Heart and vessels, 23, 5, 334, 40, Sep. 2008, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Overview image of the lumen and vessel wall in coronary CT angiography.
Masahiro Jinzaki, Minoru Yamada, Kozo Sato, Yutaka Tanami, Toshihisa Anzai, Kosuke Sasaki, Sachio Kuribayashi
Circulation journal : official journal of the Japanese Circulation Society, 72, 4, 671, 3, Apr. 2008, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Comparison of the effects of carvedilol and metoprolol on exercise ventilatory efficiency in patients with congestive heart failure.
Masaharu Kataoka, Toru Satoh, Tsutomu Yoshikawa, Iwao Nakamura, Takashi Kohno, Akihiro Yoshizawa, Toshihisa Anzai, Satoshi Ogawa
Circulation journal : official journal of the Japanese Circulation Society, 72, 3, 358, 63, Mar. 2008, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Erratum: A 19-year-old man with myocardial infarction and sitosterolemia (Internal Medicine (2003) vol. 42 (7) (591))
Takaharu Katayama, Toru Satoh, Takashi Yagi, Nobuyoshi Hirose, Yasuo Kuita, Toshihisa Anzai, Yasushi Asakura, Tsutomu Yoshikawa, Hideo Mitamura, Satoshi Ogawa
Internal Medicine, 47, 3, 191, 01 Feb. 2008, [Peer-reviewed]
English, Scientific journal

Genetic ablation of angiotersin II type 1a receptor has a beneficial effect on diabetes-induced cardiomyopathy by expressing heat shock proteins and by inhibiting apoptosis
Yuji Nagatomo, Tomomi Meguro, Kimi Koide, Toshihisa Anzai, Satoshi Ogawa, Tsutomu Yoshikawa
CIRCULATION, 116, 16, 310, 310, Oct. 2007, [Peer-reviewed]
English

Effects of beta-blocker therapy on high sensitivity c-reactive protein, oxidative stress, and cardiac function in patients with congestive heart failure.
Yuji Nagatomo, Tsutomu Yoshikawa, Takashi Kohno, Akihiro Yoshizawa, Toshihisa Anzai, Tomomi Meguro, Toru Satoh, Satoshi Ogawa
Journal of cardiac failure, 13, 5, 365, 71, Jun. 2007, [Peer-reviewed], [International Magazine]
English, Scientific journal

Increased body temperature after reperfused acute myocardial infarction is associated with adverse left ventricular remodeling.
Kotaro Naito, Toshihisa Anzai, Tsutomu Yoshikawa, Yuichiro Maekawa, Yasuo Sugano, Takashi Kohno, Keitaro Mahara, Teruo Okabe, Yasushi Asakura, Satoshi Ogawa
Journal of cardiac failure, 13, 1, 25, 33, Feb. 2007, [Peer-reviewed], [International Magazine]
English, Scientific journal

Impact of serum C-reactive protein elevation on the left ventricular spherical change and the development of mitral regurgitation after anterior acute myocardial infarction.
Takashi Kohno, Toshihisa Anzai, Kotaro Naito, Yohei Ohno, Hidehiro Kaneko, Hui-Chong Li, Yasuo Sugano, Yuichiro Maekawa, Shiro Iwanaga, Yasushi Asakura, Tsutomu Yoshikawa, Satoshi Ogawa
Cardiology, 107, 4, 386, 94, 2007, [Peer-reviewed], [International Magazine]
English, Scientific journal

Novel method of displaying coronary CT angiography: Angiographic view.
Masahiro Jinzaki, Kozo Sato, Yutaka Tanami, Minoru Yamada, Sachio Kuribayashi, Toshihisa Anzai, Yasushi Asakura, Satoshi Ogawa
Circulation journal : official journal of the Japanese Circulation Society, 70, 12, 1661, 2, Dec. 2006, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Genetic ablation of angiotensin II type1a receptor ameliorates cardiac diastolic dysfunction induced by diabetes mellitus through the improvement of calcium handling
Yuji Nagatomo, Tomomi Meguro, Hitomi Saito, Jun Katada, Toshihisa Anzai, Satoshi Ogawa, Tsutomu Yosikawa
CIRCULATION, 114, 18, 151, 151, Oct. 2006, [Peer-reviewed]
English

Presence of autoantibody directed against ss-adrenergic receptors is associated with amelioration of cardiac dysfunction during ss-blocker therapy for congestive heart failure
Yuji Nagatomo, Tsutomu Yosikawa, Takashi Kohno, Akihiro Yoshizawa, Akiyasu Baba, Toshihisa Anzai, Tomomi Meguro, Toru Sato, Satoshi Ogawa
CIRCULATION, 114, 18, 667, 667, Oct. 2006, [Peer-reviewed]
English

Presence of autoantibody against b1-adrenergic receptors is associated with amelioration of cardiac function during b-blocker therapy for congestive heart failure
Yuji Nagatomo, Tsutomu Yoshikawa, Takashi Kohno, Akihiro Yoshizawa, Akiyasu Baba, Toshihisa Anzai, Tomomi Meguro, Toru Sato, Satoshi Ogawa
JOURNAL OF CARDIAC FAILURE, 12, 8, S172, S172, Oct. 2006, [Peer-reviewed]
English

Mineralocorticoid receptor blockade arrests pressure overload-induced left ventricular hypertrophy and preserves cardiac function in angiotensin II type 1a receptor knockout mice
Tomomi Meguro, Tsutomu Yoshikawa, Jun Katada, Hitomi Saito, Toshihisa Anzai, Yuji Nagatomo, Satoshi Ogawa
CIRCULATION, 114, 18, 150, 150, Oct. 2006, [Peer-reviewed]
English

Antigen-specific effects of autoantibodies against sarcolemmal Na-K-ATPase pump in immunized cardiomyopathic rabbits.
Akiyasu Baba, Tsutomu Yoshikawa, Michikado Iwata, Toshihisa Anzai, Iwao Nakamura, Yumiko Wainai, Satoshi Ogawa, Michael Fu
International journal of cardiology, 112, 1, 15, 20, 10 Sep. 2006, [Peer-reviewed], [International Magazine]
English, Scientific journal

心筋症の診断と治療 up to date 液性免疫異常からみた心筋症の診断と治療　　　　　　　　　　　　　　　
馬場 彰泰, 吉川 勉, 長友 祐司, 栗田 康生, 内藤 広太郎, 吉澤 彰宏, 家田 真樹, 安斎 俊久, 島田 恵, 松原 隆, 赤石 誠, 朝倉 靖, 岩永 史郎, 熊谷 裕生, 小川 聡
Journal of Cardiology, 48, Suppl.I, 154, 154, (一社)日本心臓病学会, Sep. 2006, [Peer-reviewed]
Japanese

Aging adversely affects postinfarction inflammatory response and early left ventricular remodeling after reperfused acute anterior myocardial infarction.
Keitaro Mahara, Toshihisa Anzai, Tsutomu Yoshikawa, Yuichiro Maekawa, Teruo Okabe, Yasushi Asakura, Toru Satoh, Hideo Mitamura, Masahiro Suzuki, Akira Murayama, Satoshi Ogawa
Cardiology, 105, 2, 67, 74, 2006, [Peer-reviewed], [International Magazine]
English, Scientific journal

Carvedilol exerts more potent antiadrenergic effect than metoprolol in heart failure.
Takashi Kohno, Tsutomu Yoshikawa, Akihiro Yoshizawa, Iwao Nakamura, Toshihisa Anzai, Toru Satoh, Satoshi Ogawa
Cardiovascular drugs and therapy, 19, 5, 347, 55, Oct. 2005, [Peer-reviewed], [International Magazine]
English, Scientific journal

Serum C-reactive protein elevation predicts poor clinical outcome in patients with distal type acute aortic dissection: association with the occurrence of oxygenation impairment.
Yasuo Sugano, Toshihisa Anzai, Tsutomu Yoshikawa, Toru Satoh, Shiro Iwanaga, Takeharu Hayashi, Yuichiro Maekawa, Hideyuki Shimizu, Ryohei Yozu, Satoshi Ogawa
International journal of cardiology, 102, 1, 39, 45, 22 Jun. 2005, [Peer-reviewed], [International Magazine]
English, Scientific journal

Persistent cardiac aldosterone synthesis in angiotensin II type 1A receptor-knockout mice after myocardial infarction.
Jun Katada, Tomomi Meguro, Hitomi Saito, Akira Ohashi, Toshihisa Anzai, Satoshi Ogawa, Tsutomu Yoshikawa
Circulation, 111, 17, 2157, 64, 03 May 2005, [Peer-reviewed], [International Magazine]
English, Scientific journal

Oral sildenafil improves primary pulmonary hypertension refractory to epoprostenol.
Masaharu Kataoka, Toru Satoh, Tomohiro Manabe, Toshihisa Anzai, Tsutomu Yoshikawa, Hideo Mitamura, Satoshi Ogawa
Circulation journal : official journal of the Japanese Circulation Society, 69, 4, 461, 5, Apr. 2005, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Granulocyte colony-stimulating factor attenuates early ventricular expansion after experimental myocardial infarction.
Yasuo Sugano, Toshihisa Anzai, Tsutomu Yoshikawa, Yuichiro Maekawa, Takashi Kohno, Keitaro Mahara, Kotaro Naito, Satoshi Ogawa
Cardiovascular research, 65, 2, 446, 56, 01 Feb. 2005, [Peer-reviewed], [International Magazine]
English, Scientific journal

Relation of stent overexpansion to the angiographic no-reflow phenomenon in intravascular ultrasound-guided stent implantation for acute myocardial infarction.
Yuichiro Maekawa, Yasushi Asakura, Toshihisa Anzai, Shiro Ishikawa, Teruo Okabe, Tsutomu Yoshikawa, Satoshi Ogawa
Heart and vessels, 20, 1, 13, 8, Feb. 2005, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Effect of granulocyte-macrophage colony-stimulating factor inducer on left ventricular remodeling after acute myocardial infarction.
Yuichiro Maekawa, Toshihisa Anzai, Tsutomu Yoshikawa, Yasuo Sugano, Keitaro Mahara, Takashi Kohno, Toshiyuki Takahashi, Satoshi Ogawa
Journal of the American College of Cardiology, 44, 7, 1510, 20, 06 Oct. 2004, [Peer-reviewed], [International Magazine]
English, Scientific journal

Marked improvement with sildenafil in a patient with primary pulmonary hypertension unresponsive to epoprostenol.
Masaharu Kataoka, Toru Satoh, Tomohiro Manabe, Toshihisa Anzai, Tsutomu Yoshikawa, Hideo Mitamura, Satoshi Ogawa
Internal medicine (Tokyo, Japan), 43, 10, 945, 50, Oct. 2004, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Angiotensin receptor blockade improves myocardial beta-adrenergic receptor signaling in postinfarction left ventricular remodeling: a possible link between beta-adrenergic receptor kinase-1 and protein kinase C epsilon isoform.
Toshiyuki Takahashi, Toshihisa Anzai, Tsutomu Yoshikawa, Yuichiro Maekawa, Keitaro Mahara, Michikado Iwata, H Kirk Hammond, Satoshi Ogawa
Journal of the American College of Cardiology, 43, 1, 125, 32, 07 Jan. 2004, [Peer-reviewed], [International Magazine]
English, Scientific journal

Serum C-reactive protein elevation in left ventricular remodeling after acute myocardial infarction--role of neurohormones and cytokines.
Toshiyuki Takahashi, Toshihisa Anzai, Tsutomu Yoshikawa, Yuichiro Maekawa, Yasushi Asakura, Toru Satoh, Hideo Mitamura, Satoshi Ogawa
International journal of cardiology, 88, 2-3, 257, 65, Apr. 2003, [Peer-reviewed], [International Magazine]
English, Scientific journal

New horizons of congestive heart failure for the 21 ^st century : Immunological approach
Tsutomu Yoshikawa, Akiyasu Baba, Toshihisa Anzai
Respiration and Circulation, 50, 10, 999, 1006, (株)医学書院, Oct. 2002, [Peer-reviewed]
Japanese

Effect of preinfarction angina pectoris on ST-segment resolution after primary coronary angioplasty for acute myocardial infarction.
Toshiyuki Takahashi, Toshihisa Anzai, Tsutomu Yoshikawa, Yuichiro Maekawa, Yasushi Asakura, Toru Satoh, Hideo Mitamura, Satoshi Ogawa
The American journal of cardiology, 90, 5, 465, 9, 01 Sep. 2002, [Peer-reviewed], [International Magazine]
English, Scientific journal

右房内血栓,回盲部潰瘍を伴ったBehcet病の一例
吉澤 彰宏, 松下 健一, 佐藤 徹, 栗田 康生, 安斎 俊久, 岩永 史郎, 吉川 勉, 三田村 秀雄, 小川 聡, 四津 良平
Circulation Journal, 66, Suppl.II, 890, 890, (一社)日本循環器学会, Apr. 2002
Japanese

梅毒性大動脈炎による重症大動脈弁逆流(AR)の一例
菊池 真大, 杵渕 修, 佐藤 徹, 前川 裕一郎, 栗田 康生, 安斎 俊久, 岩永 史郎, 吉川 勉, 三田村 秀雄, 小川 聡
Circulation Journal, 66, Suppl.II, 906, 906, (一社)日本循環器学会, Apr. 2002
Japanese

Prognostic significance of peripheral monocytosis after reperfused acute myocardial infarction:a possible role for left ventricular remodeling.
Yuichiro Maekawa, Toshihisa Anzai, Tsutomu Yoshikawa, Yasushi Asakura, Toshiyuki Takahashi, Shiro Ishikawa, Hideo Mitamura, Satoshi Ogawa
Journal of the American College of Cardiology, 39, 2, 241, 6, 16 Jan. 2002, [Peer-reviewed], [International Magazine]
English, Scientific journal

急性心筋梗塞(AMI)におけるstentingとno reflowとの関連　　　　　　　　　　　　　　　
前川 裕一郎, 朝倉 靖, 石川 士郎, 河村 朗夫, 高橋 暁行, 山根 明子, 安斎 俊久, 吉川 勉, 小川 聡
Journal of Cardiology, 36, Suppl.I, 126, 126, (一社)日本心臓病学会, Aug. 2000
Japanese

心不全の病態診断 情報を如何に臨床応用するか βアドレナリン受容体自己抗体を用いた拡張型心筋症患者の突然死の予測　　　　　　　　　　　　　　　
吉川 勉, 岩田 道圭, 馬場 彰泰, 安斎 俊久, 小川 聡
Journal of Cardiology, 36, Suppl.I, 96, 96, (一社)日本心臓病学会, Aug. 2000, [Peer-reviewed]
Japanese

心不全急性増悪期における強心薬としては何が適当か? カテコラミンとフォスフォジエステラーゼ阻害薬の比較試験
河村 朗夫, 吉川 勉, 林 丈晴, 高橋 寿由樹, 中村 岩男, 馬場 彰泰, 安斎 俊久, 高橋 栄一, 佐藤 徹, 小川 聡
Japanese Circulation Journal, 64, Suppl.I, 339, 339, (一社)日本循環器学会, Mar. 2000, [Peer-reviewed]
Japanese

Adenylylcyclase increases responsiveness to catecholamine stimulation in transgenic mice.
M H Gao, N C Lai, D M Roth, J Zhou, J Zhu, T Anzai, N Dalton, H K Hammond
Circulation, 99, 12, 1618, 22, 30 Mar. 1999, [International Magazine]
English, Scientific journal, BACKGROUND: The cellular content of cAMP generated by activation of adenylylcyclase (AC) through the beta-adrenergic receptor (betaAR) is a key determinant of a cell's response to catecholamine stimulation. We tested the hypothesis that increased AC content, independently of betaAR number, increases responsiveness to catecholamine stimulation in vivo. METHODS AND RESULTS: Transgenic mice with cardiac-directed expression of ACVI showed increased transgene AC expression but no change in myocardial betaAR number or G-protein content. When stimulated through the betaAR, cardiac function was increased, and cardiac myocytes showed increased cAMP production. In contrast, basal cAMP and cardiac function were normal, and long-term transgene expression was not associated with abnormal histological findings or deleterious changes in cardiac function. CONCLUSIONS: The amount of AC sets a limit on cardiac beta-adrenergic signaling in vivo, and increased AC, independent of betaAR number and G-protein content, provides a means to regulate cardiac responsiveness to betaAR stimulation. Overexpressing an effector (AC) does not alter transmembrane signaling except when receptors are activated, in contrast to receptor/G-protein overexpression, which yields continuous activation and has detrimental consequences. Our findings establish the importance of AC content in modulating beta-adrenergic signaling in the heart, suggesting a new target for safely increasing cardiac responsiveness to betaAR stimulation.

Baroreceptor sensitivity during the compensatory phase of left ventricular overloading
H Nishimura, T Yoshikawa, T Anzai, A Baba, N Kobayashi, Y Wainai, S Ogawa
JAPANESE CIRCULATION JOURNAL-ENGLISH EDITION, 62, 10, 773, 778, Oct. 1998, [Peer-reviewed], [Domestic magazines]
English, Scientific journal

Dissociation between regional dysfunction and beta-adrenergic receptor signaling in heart failure
T Anzai, NC Lai, MH Gao, HK Hammond
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 275, 4, H1267, H1273, Oct. 1998, [Peer-reviewed]
English, Scientific journal

Serum C-reactive Protein Elevation in Acute Myocardial Infarction: A possible prognostic determinant of postinfarction ventricular remodeling　　　　　　　　　　　　　　　
Tsutomu Yoshikawa, Toshihisa Anzai
Respiration and Circulation, 46, 5, 477, 482, 1998
Japanese, Scientific journal

Adenylyl cyclase and G protein receptor kinase expression during development of heart failure
PP Ping, T Anzai, MH Gao, HK Hammond
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 273, 2, H707, H717, Aug. 1997, [Peer-reviewed]
English, Scientific journal

EFFECT ON SHORT-TERM PROGNOSIS AND LEFT-VENTRICULAR FUNCTION OF ANGINA-PECTORIS PRIOR TO FIRST Q-WAVE ANTERIOR WALL ACUTE MYOCARDIAL-INFARCTION
T ANZAI, T YOSHIKAWA, Y ASAKURA, S ABE, T MEGURO, M AKAISHI, H MITAMURA, S HANDA, S OGAWA
AMERICAN JOURNAL OF CARDIOLOGY, 74, 8, 755, 759, Oct. 1994, [Peer-reviewed], [International Magazine]
English, Scientific journal

Myelodysplastic syndrome associated with immunoblastic lymphadenopathy-like T-cell lymphoma: Simultaneous clinical improvement with chemotherapy
Toshihisa Anzai, Wataru Hirose, Haruyuki Nakane, Mitsuhiro Kawagoe, Toshiaki Kawai, Kiyoaki Watanabe
Japanese Journal of Clinical Oncology, 24, 2, 106, 110, 1994, [Peer-reviewed]
English, Scientific journal

Guillain-Barré Syndrome with Bilateral Tonic Pupils
Toshihisa Anzai, Kazushi Takahashi, Tetsuji Katayama
Internal Medicine, 33, 4, 248, 251, 1994, [Peer-reviewed]
English, Scientific journal

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

A case of ventricular tachycardia after myocardial infarction in which two bystanders were considered to be connected to a common pathway
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, 2024

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

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

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

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

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

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

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

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

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

Biopsy-proven cardiac sarcoidosis mimicking apical hypertrophic cardiomyopathy
Kei Kawakami, Kazunori Omote, Satonori Tsuneta, Toshiyuki Nagai, Toshihisa Anzai, European Heart Journal Cardiovascular Imaging, 25, 1, E57, 01 Jan. 2024
Report scientific journal

Focal myocarditis associated with immune checkpoint inhibitor therapy
Mizuki Hayashizaki, Kazunori Omote, Satonori Tsuneta, Toshiyuki Nagai, Toshihisa Anzai, European Heart Journal Cardiovascular Imaging, 24, 12, E308, 01 Dec. 2023
Report scientific journal

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

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

Application of an Echocardiographic Scoring System of Left Ventricular Filling Pressure for Patients with Aortic Stenosis
青柳裕之, 岩野弘幸, 後藤真奈, 鈴木ゆき乃, 村山迪史, 横山しのぶ, 西野久雄, 中鉢雅大, 中村公亮, 玉置陽生, 本居昂, 石坂傑, 加賀早苗, 神谷究, 永井利幸, 安斉俊久, 日本循環器学会学術集会(Web), 87th, 2023

Head-to-head comparison between hepatic vein flow and superior vena cava flow patterns analysis for predicting elevated right atrial pressure
村山迪史, 村山迪史, 加賀早苗, 加賀早苗, 境田ひな, 小野田愛梨, 中鉢雅大, 西野久雄, 横山しのぶ, 石坂傑, 岩野弘幸, 岩野弘幸, 安斉俊久, 超音波医学 Supplement, 50, 2023

心不全患者における複数の超音波指標を組み合わせたうっ血肝診断モデルの確立
小野田愛梨, 村山迪史, 加賀早苗, 中鉢雅大, 横山しのぶ, 西野久雄, 石坂傑, 本居昴, 青柳裕之, 玉置陽生, 中村公亮, 岩野弘幸, 安斉俊久, 日本循環器学会学術集会(Web), 87th, 2023

超音波法を用いたスコアリングによるうっ血肝診断と予後予測
小野田愛梨, 村山迪史, 村山迪史, 加賀早苗, 加賀早苗, 工藤悠輔, 岩井孝仁, 中鉢雅大, 横山しのぶ, 西野久雄, 西田睦, 石坂傑, 岩野弘幸, 岩野弘幸, 安斉俊久, 日本超音波検査学会学術集会講演抄録集(Web), 48th, 2023

抗ミトコンドリアM2抗体陽性筋炎17例の臨床的特徴
長井 梓, 永井 利幸, 矢口 裕章, 藤井 信太朗, 上床 尚, 白井 慎一, 岩田 育子, 松島 理明, 堀内 一宏, 浦 茂久, 安斉 俊久, 矢部 一郎, 神経治療学, 39, 6, S263, S263, Oct. 2022
(一社)日本神経治療学会, Japanese

【循環器薬の使い方-使い分け,モニタリング,導入・中止のタイミング】心不全 RAS阻害薬からARNIまで
小林 雄太, 安斉 俊久, 循環器ジャーナル, 70, 2, 218, 224, Apr. 2022
(株)医学書院, Japanese

SGLT2阻害薬はミトコンドリア機能の改善を介し膵β細胞量・機能を保護する　　　　　　　　　　　　　　　
山内 裕貴, 中村 昭伸, 横田 卓, 高橋 清彦, 川田 晋一朗, 土田 和久, 大森 一乃, 野本 博司, 亀田 啓, 曹 圭龍, 安斉 俊久, 田中 伸哉, 寺内 康夫, 三好 秀明, 渥美 達也, 日本内分泌学会雑誌, 98, 1, 361, 361, Apr. 2022
(一社)日本内分泌学会, Japanese

【お薬立ちBOOK2022 解剖生理・病態生理から薬学管理へ】病態生理を踏まえた薬物治療・薬学管理へ 循環器疾患 急性心不全、慢性心不全、うっ血性心不全　　　　　　　　　　　　　　　
天木 誠, 安斉 俊久, 薬局, 73, 4, 957, 965, Mar. 2022
(株)南山堂, Japanese

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, Mar. 2022
(一社)日本循環器学会, English

【慢性心不全の薬物治療】総論 フォーカスアップデートの心不全治療アルゴリズムを読む 左室駆出率の保たれた心不全　　　　　　　　　　　　　　　
安斉 俊久, 日本内科学会雑誌, 111, 2, 213, 220, Feb. 2022
(一社)日本内科学会, Japanese

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

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

ガイドラインに基づく右房圧推定における副次的指標の再考
村山迪史, 村山迪史, 加賀早苗, 岡田一範, 小野田愛梨, 種村明日香, 中鉢雅大, 横山しのぶ, 西野久雄, 西田睦, 辻永真吾, 岩野弘幸, 岩野弘幸, 安斉俊久, 日本超音波検査学会学術集会講演抄録集(Web), 47th, 2022

Influencing factors for the overestimation of severity of pulmonary regurgitation by Doppler echocardiography
本居昂, 岩野弘幸, 岩野弘幸, 常田慧徳, 村山迪史, 加賀早苗, 青柳裕之, 玉置陽生, 石坂傑, 千葉泰之, 辻永真吾, 種村明日香, 横山しのぶ, 中鉢雅大, 西野久雄, 岡田一範, 武田充人, 安斉俊久, 日本成人先天性心疾患学会雑誌(Web), 11, 1, 2022

J-CLEAR通信 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, 日本医事新報, 5096, 36, 40, Dec. 2021
(株)日本医事新報社, Japanese

注目の新薬 ベリキューボ(ベルイシグアト)
安斉 俊久, 診断と治療, 109, 10, 1447, 1452, Oct. 2021
(株)診断と治療社, Japanese

【予防・治療・緩和ケアの最重要ポイントを押さえる心不全治療アップデート】心不全の悪化予防 心不全チーム
佐藤 琢真, 永井 利幸, 安斉 俊久, 薬事, 63, 12, 2479, 2436, Sep. 2021
(株)じほう, Japanese

MitraClipを用いた経皮的僧帽弁接合修復術により強心薬を離脱できた重症心不全の一例　　　　　　　　　　　　　　　
高橋 昌寛, 辻永 真吾, 高橋 勇樹, 佐藤 琢真, 内藤 正一郎, 青柳 裕之, 小林 雄太, 神谷 究, 岩野 弘幸, 永井 利幸, 安斉 俊久, 日本心臓病学会学術集会抄録, 69回, O, 267, Sep. 2021
(一社)日本心臓病学会, Japanese

【心不全/糖尿病パンデミック的現状とICU】心不全薬物治療の新展開
多田 篤司, 安斉 俊久, ICUとCCU, 45, 8, 463, 470, Aug. 2021
医学図書出版(株), Japanese

【循環器病の対策推進計画とトピックス】心不全診療と推進基本計画
安斉 俊久, 循環器内科, 90, 1, 22, 27, Jul. 2021
(有)科学評論社, Japanese

【二次性心筋症-Present and Future】収縮不全を主徴とする二次性心筋症 がん治療関連心機能障害(CTRCD)
辻永 真吾, 安斉 俊久, 医学のあゆみ, 277, 5, 400, 405, May 2021
医歯薬出版(株), Japanese

【合併症とそのマネージメント】腎障害と対処法　　　　　　　　　　　　　　　
山下 武廣, 安斉 俊久, Coronary Intervention, 17, 3, 76, 81, May 2021
(株)メディアルファ, Japanese

SGLT2阻害薬はミトコンドリア機能の改善を介し膵β細胞を保護する　　　　　　　　　　　　　　　
山内 裕貴, 中村 昭伸, 横田 卓, 高橋 清彦, 川田 晋一朗, 土田 和久, 大森 一乃, 野本 博司, 亀田 啓, 曹 圭龍, 安斉 俊久, 田中 伸哉, 寺内 康夫, 三好 秀明, 渥美 達也, 糖尿病, 64, Suppl.1, III, 6, May 2021
(一社)日本糖尿病学会, Japanese

【循環器疾患 緩和ケアの現状を識る】識る 循環器緩和ケアチームのあり方
佐藤 琢真, 永井 利幸, 安斉 俊久, Heart View, 25, 4, 332, 337, Apr. 2021
(株)メジカルビュー社, Japanese

【新規心不全治療薬の使い方】ベルイシグアト
安斉 俊久, 医学のあゆみ, 277, 4, 285, 290, Apr. 2021
医歯薬出版(株), Japanese

新規の慢性心不全治療薬ベルイシグアト
安斉 俊久, 循環器内科, 89, 4, 470, 476, Apr. 2021
(有)科学評論社, Japanese

負荷心エコー図検査の現状と未来 負荷心エコー図検査を活かす 検査導入後5年間の取り組み　　　　　　　　　　　　　　　
辻永 真吾, 岩野 弘幸, 青柳 裕之, 玉置 陽生, 本居 昂, 石坂 傑, 千葉 泰之, 永井 利幸, 安斉 俊久, 超音波医学, 48, Suppl., S212, S212, Apr. 2021
(公社)日本超音波医学会, Japanese

【二次性心筋疾患を見逃すな!】心筋炎の診断と治療 急性期、慢性期の治療は?
辻永 真吾, 安斉 俊久, 循環器内科, 89, 3, 308, 315, Mar. 2021
(有)科学評論社, Japanese

【病気とくすり2021 基礎と実践Expert's Guide】循環器系の病気とくすり 循環器系疾患 心不全　　　　　　　　　　　　　　　
天木 誠, 安斉 俊久, 和田 恭一, 薬局, 72, 4, 932, 951, Mar. 2021
(株)南山堂, Japanese

循環器疾患における緩和ケアについてのJCS 2021/JHFS 2021 statement(JCS 2021/JHFS 2021 Statement on Palliative Care in Cardiovascular Diseases)　　　　　　　　　　　　　　　
安斉 俊久, 日本循環器学会学術集会抄録集, 85回, RT14, 1, Mar. 2021
(一社)日本循環器学会, English

心内血流パラメータと心臓形態の関連(Relationships between Intra-cardiac Flow Parameters and Cardiac Morphology)　　　　　　　　　　　　　　　
岩野 弘幸, 安斉 俊久, 日本循環器学会学術集会抄録集, 85回, TP02, 2, Mar. 2021
(一社)日本循環器学会, English

心不全の重症化予防の取り組み　　　　　　　　　　　　　　　
安斉 俊久, 日本循環器学会学術集会抄録集, 85回, LS26, LS26, Mar. 2021
(一社)日本循環器学会, Japanese

循環器疾患患者のこころの問題にどう向き合うか?(緩和ケアも含めて) 当院における心不全緩和ケアチームの立ち上げと現状　　　　　　　　　　　　　　　
阿部 隆宏, 佐藤 琢真, 加藤 美香, 笠谷 美鈴, 成田 尚, 福澤 宏之, 片山 真育, 池田 陽子, 小島 尚子, 杉本 由佳, 永井 利幸, 安斉 俊久, 日本循環器学会学術集会抄録集, 85回, CS5, 3, Mar. 2021
(一社)日本循環器学会, Japanese

心不全療養指導士を取得した理学療法士としての活動
阿部隆宏, 永井利幸, 安斉俊久, 日本心不全学会学術集会プログラム・抄録集, 25th, 2021

心不全緩和ケアチームによる介入
阿部隆宏, 佐藤琢真, 永井利幸, 安斉俊久, 日本心不全学会学術集会プログラム・抄録集, 25th, 2021

臨床高血圧125周年 論点の整理と将来展望 高血圧心としてのHFpEFの病態と適正治療のあり方
安斉 俊久, Therapeutic Research, 42, 1, 15, 20, Jan. 2021
ライフサイエンス出版(株), Japanese

心臓サルコイドーシス患者における血清可溶性インターロイキン2レセプター高値は長期予後と関連する
小林雄太, 永井利幸, 平田健司, 常田慧徳, 加藤喜哉, 小森山弘和, 神谷究, 小西崇夫, 佐藤琢真, 表和徳, 工藤與亮, 今野哲, 安斉俊久, 日本サルコイドーシス/肉芽腫性疾患学会雑誌, 41, サプリメント号, 62, 62, 2021
日本サルコイドーシス, Japanese

Importance of Atrial Fibrillation and Right Atrial Remodeling in Functional Tricuspid Regurgitation in Heart Failure with Preserved Ejection Fraction
原田智成, 小保方優, 表和徳, 岩野弘幸, 吉田くに子, 加藤寿光, 永井利幸, 安斉俊久, 倉林正彦, 日本循環器学会学術集会(Web), 85th, OJ88, 6, 2021
(一社)日本循環器学会, English

慢性心不全における右室cardiac power outputの意義
千葉泰之, 岩野弘幸, 岩野弘幸, 本居昂, 石坂傑, 辻永真吾, 村山迪史, 横山しのぶ, 中鉢雅大, 西野久雄, 岡田一範, 加賀早苗, 神谷究, 永井利幸, 安斉俊久, 日本心臓病学会学術集会(Web), 69th, 2021

心エコー法による新たな左房圧指標を用いたHFpEFの予後予測に関する検討
村山迪史, 岩野弘幸, 岩野弘幸, 岩野弘幸, 表和徳, 原田智成, 小保方優, 加藤寿光, 中鉢雅弘, 西野久雄, 横山しのぶ, 辻永真吾, 千葉泰之, 石坂傑, 本居昂, 西田睦, 安斉俊久, 日本心不全学会学術集会プログラム・抄録集, 25th, 2021

A case of ventricular tachycardia in a patient with non ischemic cardiomyopathy; tachycardia showing an alternating QRS morphology with a reentry mechanism maintained by alternating the different slow conduction zones of the intramural tissue
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

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

MRIのT1mappingによる心筋細胞外容積分画は筋ジストロフィーによるびまん性心筋障害の検出に有用である
相川忠夫, 小梁川和宏, 小林雄太, 武田充人, 白石秀明, 常田慧徳, 岩野弘幸, 永井利幸, 安斉俊久, 真鍋徳子, 日本心血管画像動態学会プログラム・抄録集, 31st (CD-ROM), 2021

Clinical utility of stress echocardiography: summary of 5 years’ experience
辻永真吾, 岩野弘幸, 青柳裕之, 玉置陽生, 本居昂, 石坂傑, 千葉泰之, 永井利幸, 安斉俊久, 超音波医学 Supplement, 48, 2021

三次元スペックルトラッキング法による右室機能解析に関する初期検討　　　　　　　　　　　　　　　
岡田 一範, 加賀 早苗, 上田 龍一郎, 柳 裕介, 相庭 美穂, 政氏 伸夫, 三神 大世, 中鉢 雅大, 岩野 弘幸, 安斉 俊久, 超音波医学, 47, Suppl., S221, S221, Nov. 2020
(公社)日本超音波医学会, Japanese

Influence of Advanced Pulmonary Vascular Remodeling on Accuracy of Echocardiographic Parameters of Left Ventricular Filling Pressure
Yasuyuki Chiba, Hiroyuki Iwano, Sanae Kaga, Mio Shinkawa, Michito Murayama, Hiroshi Ohira, Ko Motoi, Suguru Ishizaka, Shingo Tsujinaga, Shinobu Yokoyama, Masahiro Nakabachi, Hisao Nishino, Kazunori Okada, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai, CIRCULATION, 142, Nov. 2020
English, Summary international conference

Left Ventricular External Work as a Marker of Cardiac Functional Recovery and Outcome After Transcatheter Aortic Valve Replacement in Patients With Aortic Stenosis
Shingo Tsujinaga, Hiroyuki Iwano, Ko Motoi, Yasuyuki Chiba, Suguru Ishizaka, Michito Murayama, Masahiro Nakabachi, Shinobu Yokoyama, Hisao Nishino, Kazunori Okada, Sanae Kaga, Kiwamu Kamiya, Toshiyuki Nagai, Toshihisa Anzai, CIRCULATION, 142, Nov. 2020
English, Summary international conference

心臓サルコイドーシス患者における左室駆出率低値と血清ACE活性高値は組織診断陽性と関連する
小森山 弘和, 表 和徳, 永井 利幸, 加藤 喜哉, 永野 伸卓, 神谷 究, 小西 崇夫, 草野 研吾, 植田 初江, 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, 52, 52, Oct. 2020
日本サルコイドーシス, Japanese

心臓サルコイドーシス患者におけるステロイド開始前心室再分極過程のばらつきは長期心事故発生と関連する
小林 雄太, 永井 利幸, 神谷 究, 小西 崇夫, 佐藤 琢真, 加藤 喜哉, 小森山 弘和, 草野 研吾, 植田 初江, 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, Oct. 2020
日本サルコイドーシス, Japanese

【循環器疾患バイオマーカー 有用性と可能性】診る 欧米のエビデンスに基づいた心不全ガイドラインは日本人に当てはまるか? バイオマーカーを中心に
永井 利幸, 安斉 俊久, Heart View, 24, 10, 937, 943, Oct. 2020
(株)メジカルビュー社, Japanese

【循環器疾患のPrecision Medicine】臨床 心不全個別化医療　　　　　　　　　　　　　　　
永井 利幸, 安斉 俊久, Cardiac Practice, 31, 1, 32, 36, Oct. 2020
(株)メディカルレビュー社, Japanese

心臓サルコイドーシス患者における左室駆出率低値と血清ACE活性高値は組織診断陽性と関連する
小森山 弘和, 表 和徳, 永井 利幸, 加藤 喜哉, 永野 伸卓, 神谷 究, 小西 崇夫, 草野 研吾, 植田 初江, 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, 52, 52, Oct. 2020
日本サルコイドーシス, Japanese