Informa UK Limited Acta Medica Okayama 1751-2433 2026 Treatment strategies for pulmonary arterial hypertension associated with adult congenital heart diseases EN Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Introduction The number of patients with adult congenital heart disease (ACHD) is gradually increasing worldwide due to advances in surgical techniques and pharmacological therapies. ACHD can lead to pulmonary arterial hypertension (PAH), and treatment strategies for PAH associated with ACHD have also evolved. Areas covered Several PAH-targeted drugs including endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclin analogs are available for treatment of PAH. In this review, we summarized the current evidence regarding the use of PAH-targeted drugs in patients with PAH associated with ACHD. We also propose a ‘treat and repair’ strategy, which involves initial medical treatment to improve PAH followed by surgical or interventional repair of the systemic-to-pulmonary shunt. A PubMed literature search was conducted from 2000 to 2025. Expert opinion In cases of PAH associated with a systemic-to-pulmonary cardiac shunt, advanced PAH-targeted drugs can improve hemodynamics, and reduce the risk of cardiac defect repair and further improvement in PAH. The treat and repair strategy represents a promising therapeutic approach for PAH patients associated with systemic-to-pulmonary shunts. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2053-3624 13 1 2026 Predictive value of simple echocardiographic parameters for screening pulmonary hypertension under the revised definition: a study for general hospitals e004185 EN Yoshitake Fukuda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Satoshi Taya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yoshihiro Dohi Department of Cardiovascular Medicine, Kure Kyosai Hospital Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Background The current guideline recommends a peak tricuspid regurgitation velocity (TRV) ≥2.9 m/s on echocardiography for pulmonary hypertension (PH) screening; however, this threshold was based on the previous PH definition (mean pulmonary arterial pressure (mPAP) ≥25 mm Hg) and derived largely from PH referral centres. Methods We retrospectively analysed 755 patients who underwent both transthoracic echocardiography and right heart catheterisation at two general hospitals. The discrimination of peak TRV and estimated right atrial pressure (eRAP), derived from inferior vena cava diameter and respiratory variation, for screening for PH was assessed by receiver operating characteristic curve analysis. Optimal cut-off values were determined with the Youden Index. Results The c-statistic for peak TRV in detecting PH was 0.82 (95% CI 0.79 to 0.85). An optimal cut-off of 2.7 m/s provided higher sensitivity (72%) than the conventional 2.9 m/s threshold (60%) while maintaining high specificity (82%). In 681 patients with available TRV and eRAP data, adding eRAP improved discrimination compared with TRV alone (c-statistic 0.83 vs 0.80; net reclassification improvement=0.14, p=0.002). eRAP ≥5 mm Hg was associated with a higher risk of PH, and the combination of elevated TRV and eRAP yielded the strongest association. Conclusion For screening under the revised PH definition, a peak TRV of 2.7 m/s is suggested as the optimal cut-off. Although TRV alone showed good discriminative performance, combining it with eRAP further improved diagnostic accuracy using simple echocardiographic measures. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 16 3 2026 Protocol for an open-label, randomised, controlled trial to evaluate the efficacy and safety of sotatercept add-on therapy compared with pulmonary vasodilator-based standard of care for pulmonary vasodilator-resistant pulmonary arterial hypertension associated with unrepaired congenital shunts (atrial septal defect, ventricular septal defect or patent ductus arteriosus), including Eisenmenger syndrome: the SuMILE trial e113430 EN Keimei Yoshida Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Kazuya Hosokawa Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Takahiro Hiraide Department of Cardiology, Keio University School of Medicine Satoshi Akagi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Ejiri Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yu Taniguchi Division of Cardiovascular Medicine, Kobe University Hospital Shiro Adachi Department of Cardiology, Nagoya University Hospital Takumi Inami Department of Cardiovascular Medicine, Kyorin University School of Medicine Naohiko Nakanishi Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine Masaharu Kataoka The Second Department of Internal Medicine, University of Occupational and Environmental Health Taijyu Satoh Department of Medical Science and Innovation, SiRIUS Institute of Medical Research, Tohoku University Shunsuke Tatebe Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine Toshiro Shinke Division of Cardiology, Department of Medicine, Showa Medical University Hospital Hideshi Tomita Periatric Heart Disease and Adult Congenital Heart Disease Center, Showa Medical University Hospital Yusuke Akazawa Department of Cardiology, Pulmonology, Hypertension and Nephrology, Ehime University Graduate School of Medicine Takashi Higaki Department of Pediatric and Adolescent Therapeutic and Developmental Education, Ehime University Graduate School of Medicine Koshiro Tagawa Center for Clinical and Translational Research, Kyushu University Hospital Ayako Ishikita Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Soshun Asakawa Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Kohtaro Abe Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University Introduction Eisenmenger syndrome and pulmonary arterial hypertension (PAH) due to unrepaired congenital shunts, including atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), remain life-threatening conditions despite advances in congenital heart disease (CHD) care. In this population, vasodilator-based therapies effective in other forms of PAH have shown limited benefit, and no disease-modifying treatment has been established. Sotatercept, an activin-signalling inhibitor, improved exercise capacity and haemodynamics in phase 2/3 PAH trials; however, patients with unrepaired CHD, including Eisenmenger syndrome, were excluded. The efficacy and safety of sotatercept in this population remain unknown. Methods and analysis The SuMILE trial is a prospective, exploratory, multicentre, open-label, randomised, controlled trial conducted at 11 Japanese tertiary centres. 36 adults with vasodilator-resistant PAH due to unrepaired ASD, VSD or PDA, including Eisenmenger syndrome, will be randomised 2:1 to sotatercept add-on therapy plus vasodilator-based PAH therapy versus vasodilator-based PAH therapy alone. Sotatercept will be administered subcutaneously every 3 weeks in accordance with label-approved dose-modification rules for haemoglobin and platelet changes. The primary endpoint is the change in 6-min walk distance from baseline to week 24. Key clinical events will be independently adjudicated. Secondary endpoints include all-cause mortality or lung transplantation; pulmonary hypertension-related hospitalisation or initiation of parenteral prostacyclin and changes in WHO functional class, N-terminal pro-brain natriuretic peptide and emPHasis-10. Exploratory endpoints include genotype, right heart catheterisation and cardiac MRI parameters. The primary analysis will use ANCOVA, adjusting for baseline 6-min walk distance and randomisation stratum in the intention-to-treat population. Ethics and dissemination The protocol has been reviewed and approved by the certified central review board (Kyushu University Hospital Clinical Ethics Review Board) and participating institutions. Written informed consent will be obtained from all participants. Findings will be disseminated through peer-reviewed journals, scientific conferences and trial registries. Trial registration number Japan Registry of Clinical Trials no. 1071250069; ClinicalTrials.gov NCT07356778. Protocol version and date: V.1.3; 23 October 2025 No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2752-4191 5 6 2025 Sex differences in the progression of cardiovascular–kidney–metabolic syndrome oeaf162 EN Satoshi Taya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hidehiro Kaneko Department of Cardiovascular Medicine, The University of Tokyo Yuta Suzuki Department of Advanced Cardiology, The University of Tokyo Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Mizuno Department of Cardiology, Medical Quality Management Office, QI Center, St. Luke's International Hospital Toshiyuki Ko Department of Cardiovascular Medicine, The University of Tokyo Takahiro Jimba Department of Cardiovascular Medicine, The University of Tokyo Tatsuhiko Azegami Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine Akira Okada Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo Katsuhito Fujiu Department of Cardiovascular Medicine, The University of Tokyo Norifumi Takeda Department of Cardiovascular Medicine, The University of Tokyo Hiroyuki Morita Department of Cardiovascular Medicine, The University of Tokyo Kaori Hayashi Division of Nephrology, Endocrinology, and Metabolism, Department of Internal Medicine, Keio University School of Medicine Koichi Node Department of Cardiovascular Medicine, Saga University Masaomi Nangaku Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine Hideo Yasunaga Department of Clinical Epidemiology and Health Economics, School of Public Health, The University of Tokyo Norihiko Takeda Department of Cardiovascular Medicine, The University of Tokyo Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims Cardiovascular–kidney–metabolic (CKM) syndrome is a novel disease concept; however, sex differences in its progression remain uncertain. This study aimed to quantify the risk of cardiovascular disease (CVD) events across CKM stages and to explore sex differences in this association. Methods and results We included 1 332 436 individuals (581 423 males and 751 013 females) from the DeSC database between 2014 and 2023 who had no prior CVD (i.e. CKM Stage 4). CKM stages were categorized as follows: Stage 0 (no CKM risk factors); Stage 1 (excess or dysfunctional adiposity); Stage 2 [metabolic risk factors and chronic kidney diseases (CKD)], and Stage 3 (subclinical CVD). We used Cox models to examine the association of CKM stages with the risk of CVD events (newly developed CKM Stage 4), including myocardial infarction, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The progression from CKM Stages 0 to 3 showed a dose-dependent increase in adjusted hazard ratios (HR) for developing CVD events, with the highest risk at Stage 3 [1.85 (95% CI: 1.80–1.90)]. A similar pattern was observed in both males and females. However, the magnitude of associations for CKM stages 1–3 differed between the sexes: HR by Stage 1, 1.12 (1.04–1.21) vs. 1.12 (1.07–1.16); by Stage 2, 1.78 (1.69–1.88) vs. 1.43 (1.39–1.48); by Stage 3, 1.99 (1.89–2.10) vs. 1.82 (1.76–1.88); and P-for-interaction values were 0.87, < 0.001, and 0.005, respectively. Conclusion In this large nationwide cohort, CKM stage progression was associated with higher CVD risk in both sexes, with modest sex-specific differences. These findings highlight the value of CKM staging for early risk assessment, regardless of sex. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2666-0849 30 32 2025 Guide Tip Damage Due to Rotablation 105347 EN Satoshi Taya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Masatoki Yoshida Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hironobu Toda Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background: The rotational atherectomy system can effectively debulk calcified coronary lesions. However, rare complications specific to that system have been reported. Case Summary: A 77-year-old man with a heavily calcified lesion in the right coronary artery (RCA) ostium underwent percutaneous coronary intervention in an 8-F system. During the procedure, rotablation with a 2.25-mm burr was required. After the percutaneous coronary intervention, partial loss of the tip of the guide was observed. He had no clinical sequelae despite the presumed retained catheter material in his body. Discussion: Although insufficient guide coaxiality has been suggested as the primary cause of guide tip fracture during RCA ostial ablation, other factors may have contributed: the application of force to the tip and a small difference in size between the guide and the burr. Take-Home Message: When ablating RCA ostial lesions, positioning the burr platform outside the guide may help prevent similar complications in future cases. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1880-4276 41 3 2025 Acute effect of multipoint pacing and fused AV delay in patients receiving cardiac resynchronization therapy e70085 EN Masakazu Miyamoto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tomofumi Mizuno Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Ueoka Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuro Masuda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Saori Asada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoshi Kawada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure with dyssynchrony. However, one-third of patients do not respond positively to it. Recently, multipoint pacing (MPP), which involves pacing from two sites on the left ventricle, has been found to improve symptoms and hemodynamics compared to conventional CRT. An automatic fused atrioventricular (AV) delay that performs fused pacing for intrinsic conduction has also been introduced. However, the combined effect of MPP and fused AV delay on acute hemodynamics is unknown. Objective: To evaluate the acute hemodynamic effects of MPP and fused AV delay in patients undergoing CRT. Methods: A pressure wire was delivered to the left ventricle, and dp/dt was compared with single atrial stimulation pacing in 52 patients with various pacing configurations. Results: Delta dp/dt was greater in MPP than in conventional CRT (10.5 ± 1.0% vs. 8.2 ± 1.0%, p < 0.001) and in fused AV delay than in short AV delay (10.4 ± 0.8% vs. 8.3 ± 1.1, p < 0.001). Hemodynamic parameters significantly most improved with the combination of MPP and fused AV delay. Delta dp/dt was greater in LV pacing than in biventricular (BiV) pacing with MPP and fused AV delay; however, the delta QRS duration was shorter in LV pacing than in BiV pacing. Delta dp/dt and delta QRS duration were negatively correlated. The super-responder rate was 66%. Conclusion: Combining MPP and fused AV delay has an additional effect. Shortening the QRS duration can increase the dp/dt, but the estimated line differs between LV and BiV pacing. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-3747 5 1 2025 Evaluating Pericoronary Adipose Tissue Attenuation to Predict Cardiovascular Events 1 11 EN Takahiro Nishihara Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Miyoshi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Ejiri Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Center Soichiro Fuke Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital Kousuke Seiyama Department of Cardiology, Kagawa Prefectural Central Hospital Masayuki Doi Department of Cardiology, Kagawa Prefectural Central Hospital Mitsutaka Nakashima Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takashi Miki Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinsuke Yuasa Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background: Pericoronary adipose tissue attenuation (PCATA) is a novel imaging biomarker of pericoronary inflammation associated with coronary artery disease. Several studies have reported the usefulness of PCATA among people of European ethnicity; however, data are lacking concerning those of Asian ethnicity. Objectives: This multicenter study aimed to evaluate the effect of PCATA on prognosis in East Asian patients. Methods: Between August 2011 and December 2016, 2,172 patients underwent clinically indicated coronary computed tomography angiography (CTA) at 4 hospitals in Japan. Among them, 1,270 patients were analyzed. PCATA was evaluated using coronary CTA to measure pericoronary adipose tissue density surrounding the 3 major coronary arteries. The outcomes were composite cardiovascular events, including cardiovascular death and acute coronary syndrome; 33 cardiovascular events observed during a median follow-up of 6.0 years (Q1-Q3: 3.6-8.2 years). Results: Right coronary artery (RCA)-PCATA was significantly higher in patients with cardiovascular events than in those without (－63.7 ± 8.9 HU vs －67.4 ± 9.1 HU, respectively; P = 0.021). High RCA-PCATA was significantly associated with cardiovascular events in a model that included the Hisayama risk score and adverse coronary CTA findings (HR: 1.55; 95% CI: 1.07-2.24; P = 0.019). Conclusions: High RCA-PCATA showed significant association with future cardiovascular events after adjusting conventional risk factors and adverse coronary CTA findings in East Asian patients who underwent clinically indicated coronary CTA. No potential conflict of interest relevant to this article was reported.

Japanese Circulation Society Acta Medica Okayama 1346-9843 89 7 2025 Hemodynamic Changes After Wire Frame Occluders vs. Metal Mesh Devices for Atrial Septal Defect 930 938 EN Mitsutaka Nakashima Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Teiji Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Transcatheter atrial septal defect (ASD) closure is the first treatment option for secundum ASD, but parameters for optimal device selection have not been established. We compared outcomes between occluders with a wire frame and metal mesh devices. Methods and Results: This study included secundum ASD patients implanted with a wire frame occluder (GORE®CARDIOFORM ASD occluder [GCA]; W.L. Gore & Associates) or metal mesh devices (Amplatzer septal occluder device [Abbott] and Occlutech Figulla Flex II device [Occlutech]). The presence of residual shunt and B-type natriuretic peptide (BNP) levels after implantation were compared. Of the 970 patients with either GCA (n=48) or a metal mesh device (n=922; control), 42 patients from each group were analyzed after propensity score matching. The prevalence of residual shunt was significantly lower in the GCA group 1 day and 1 month after implantation (P<0.001 and P=0.017, respectively), whereas there was no significant difference between the 2 groups 6 months later (P=0.088). BNP levels at 1 month were significantly higher in the GCA group (ratio of change 1.36; 95% confidence interval [CI] 1.01–1.83), but did not differ significantly between the 2 groups at 6 months (ratio of change 1.04; 95% CI 0.65–1.65). Conclusions: Patients implanted with a wire frame occluder had a lower prevalence of residual shunt and a greater increase in BNP levels in the early period after implantation. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2772-963X 4 5 2025 Prognostic Value of Pericoronary Fat Attenuation Index on Computed Tomography for Hospitalization for Heart Failure 101685 EN Mitsutaka Nakashima Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahiro Nishihara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shohei Hara Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medicine Centre Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences BACKGROUND Pericoronary fat attenuation index (FAI) assessed on computed tomography is associated with the inflammation of the pericoronary artery. OBJECTIVES This study aimed to investigate whether pericoronary FAI predicts hospitalization for heart failure with preserved ejection fraction (HFpEF). METHODS This retrospective single-center study included 1,196 consecutive patients who underwent clinically indicated coronary computed tomography angiography (CCTA) and transthoracic echocardiography. We assessed the FAI of proximal 40-mm segments for each major epicardial coronary vessel. The primary outcome was the incidence of hospitalization for HFpEF. Patients were divided into groups based on the optimal cutoff value for predicting hospitalization for HFpEF by receiver operating characteristic curve analysis. RESULTS During a median follow-up of 4.3 years, 29 hospitalizations for HFpEF occurred. Multivariable Cox regression analysis revealed that a left anterior descending artery (LAD)-FAI >=-63.4 HU and a left circumflex artery-FAI >=-61.6 HU were significantly associated with hospitalization for HF after adjustment for age and sex (HR: 4.8; 95% CI: 2.1-10.8 and HR: 4.5; 95% CI: 2.1-9.4, respectively). The addition of LAD-FAI >-63.4 HU to a model incorporating other risk factors, including hypertension, estimated glomerular filtration rate <60 mL/min/1.73 m2, and significant stenosis on CCTA, increased the C-statistic for predicting hospitalization for HFpEF from 0.646 to 0.750 (P = 0.010). CONCLUSIONS LAD-and left circumflex artery-FAI can predict hospitalization for HFpEF in patients undergoing clinically indicated CCTA. Pericoronary inflammation may be useful for identifying patients at high risk of developing HFpEF. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1477-9560 23 1 2025 Anticoagulant effects of edoxaban in cancer and noncancer patients with venous thromboembolism 36 EN Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Naoaki Matsuo Department of General Internal Medicine 3, Kawasaki Medical School Takanori Naito Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Kuroda Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital Koji Tokioka Department of Cardiovascular Medicine, Okayama City Hospital Kunihiko Hatanaka Department of Cardiovascular Medicine, Japanese Red Cross Society Himeji Hospital Ryohei Fujimoto Department of Cardiovascular Medicine, Tsuyama Chuo Hospital Hidenaru Yamaoka Department of Cardiovascular Medicine, Okayama Rosai Hospital Yutaka Kajikawa Department of Cardiovascular Medicine, NHO Fukuyama Medical Center Kazuki Suruga Department of Cardiovascular Medicine, Okayama Medical Center Hiroki Sugiyama Department of Cardiovascular Medicine, Okayama Saiseikai General Hospital Tsuyoshi Miyaji Hosogi Hospital Yoshimasa Morimoto Department of Cardiovascular Medicine, Fukuyama City Hospital Nobuhiro Okamura Okamura Isshindow Hospital Toshihiro Sarashina Kuroda Clinic Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of General Internal Medicine 3, Kawasaki Medical School Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background Edoxaban, a direct oral anticoagulant (DOAC), is a first-line treatment for venous thromboembolism (VTE) and the suppression of VTE recurrence. In patients with cancer, however, recurrent VTE after DOAC treatment may be more common than in noncancer patients. To evaluate our hypothesis that the anticoagulation effect of edoxaban is lower in VTE patients with cancer than in noncancer patients. Methods This study was a prospective, multicenter, observational study including patients treated with edoxaban for VTE in Japan. The primary outcome was the difference in the prothrombin time (PT), activated partial thromboplastin time (APTT), and D-dimer level at 5 h after initial edoxaban administration between the cancer and noncancer groups. An additional outcome was the longitudinal change in PT and APTT from 5 h to overnight after edoxaban administration. The incidence of adverse events was further investigated. Results PT and APTT at 5 h after initial edoxaban administration were not significantly different between the cancer (n = 84) and noncancer groups (n = 138) (e.g., log-transformed APTT 3.55 vs. 3.55, p = 0.45). However, D-dimer in the cancer groups was significantly greater than that in the noncancer groups (log-transformed 1.83 vs. 1.79, p = 0.009). PT and APTT significantly decreased from 5 h to overnight after edoxaban, but a similar pattern was observed in each group. All adverse events after edoxaban administration were also similar between patients with cancer and noncancer. Conclusion PT and APTT after edoxaban administration were similar between VTE patients with cancer and noncancer groups, suggesting that edoxaban has anticoagulation effects on cancer-associated VTE similar to those of noncancer patients. Trial registration UMIN000041973; Registration Date: 2020.10.5. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 26 2 2025 Pathophysiology of Group 3 Pulmonary Hypertension Associated with Lung Diseases and/or Hypoxia 835 EN Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Taya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yukihiro Saito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Kuroda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihisa Toh Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Katanosaka Department of Pharmacy, Kinjo Gakuin University Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pulmonary hypertension associated with lung diseases and/or hypoxia is classified as group 3 in the clinical classification of pulmonary hypertension. The efficacy of existing selective pulmonary vasodilators for group 3 pulmonary hypertension is still unknown, and it is currently associated with a poor prognosis. The mechanisms by which pulmonary hypertension occurs include hypoxic pulmonary vasoconstriction, pulmonary vascular remodeling, a decrease in pulmonary vascular beds, endothelial dysfunction, endothelial-to-mesenchymal transition, mitochondrial dysfunction, oxidative stress, hypoxia-inducible factors (HIFs), inflammation, microRNA, and genetic predisposition. Among these, hypoxic pulmonary vasoconstriction and subsequent pulmonary vascular remodeling are characteristic factors involving the pulmonary vasculature and are the focus of this review. Several factors have been reported to mediate vascular remodeling induced by hypoxic pulmonary vasoconstriction, such as HIF-1 alpha and mechanosensors, including TRP channels. New therapies that target novel molecules, such as mechanoreceptors, to inhibit vascular remodeling are awaited. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1880-4276 40 3 2024 Artificial intelligence to detect noise events in remote monitoring data 560 577 EN Nobuhiro Nishii Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kensuke Baba Cyber-Physical Engineering Informatics Research Core, Okayama University Ken'Ichi Morooka Division of Industrial Innovation Sciences, Graduate School of Natural Science and Technology, Okayama University Haruto Shirae Division of Industrial Innovation Sciences, Graduate School of Natural Science and Technology, Okayama University Tomofumi Mizuno Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takuro Masuda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Akira Ueoka Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Saori Asada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masakazu Miyamoto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoshi Kawada Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinsuke Yuasa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background: Remote monitoring (RM) of cardiac implantable electrical devices (CIEDs) can detect various events early. However, the diagnostic ability of CIEDs has not been sufficient, especially for lead failure. The first notification of lead failure was almost noise events, which were detected as arrhythmia by the CIED. A human must analyze the intracardiac electrogram to accurately detect lead failure. However, the number of arrhythmic events is too large for human analysis. Artificial intelligence (AI) seems to be helpful in the early and accurate detection of lead failure before human analysis. Objective: To test whether a neural network can be trained to precisely identify noise events in the intracardiac electrogram of RM data. Methods: We analyzed 21 918 RM data consisting of 12 925 and 1884 Medtronic and Boston Scientific data, respectively. Among these, 153 and 52 Medtronic and Boston Scientific data, respectively, were diagnosed as noise events by human analysis. In Medtronic, 306 events, including 153 noise events and randomly selected 153 out of 12 692 nonnoise events, were analyzed in a five-fold cross-validation with a convolutional neural network. The Boston Scientific data were analyzed similarly. Results: The precision rate, recall rate, F1 score, accuracy rate, and the area under the curve were 85.8 ± 4.0%, 91.6 ± 6.7%, 88.4 ± 2.0%, 88.0 ± 2.0%, and 0.958 ± 0.021 in Medtronic and 88.4 ± 12.8%, 81.0 ± 9.3%, 84.1 ± 8.3%, 84.2 ± 8.3% and 0.928 ± 0.041 in Boston Scientific. Five-fold cross-validation with a weighted loss function could increase the recall rate. Conclusions: AI can accurately detect noise events. AI analysis may be helpful for detecting lead failure events early and accurately. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2045-8932 13 3 2023 Impact of malnutrition on prognosis in patients with pulmonary arterial hypertension e12286 EN Mitsutaka Nakashima Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Pulmonary arterial hypertension is a life-threatening disease that coexists with right heart failure. We evaluated the relationship between malnutrition and prognosis in patients with pulmonary arterial hypertension, as malnutrition is known as a prognosis determinant in chronic heart failure. We retrospectively reviewed data of patients with pulmonary arterial hypertension before treatment. The Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Controlling Nutritional Status scores on the day of diagnosis were calculated to assess the nutritional status. Clinical endpoints were defined as composite outcomes of all-cause death or lung transplantation. Eighty patients were enrolled (mean age, 50 years; 23 men). The mean pulmonary arterial pressure was 47 ± 19 mmHg, Geriatric Nutritional Risk Index was 99.9 ± 12.0, and Prognostic Nutritional Index was 46.3 ± 10.0. The median Controlling Nutritional Status score was 2 (1–4). During the median 5.5-year follow-up period, 28 composite events occurred. Kaplan-Meier analysis demonstrated significant differences in the incidence of clinical endpoints between groups divided by each median Geriatric Nutritional Risk Index, Prognostic Nutritional Index, and Controlling Nutritional Status score (p = 0.007, 0.039, and 0.010, respectively). In multivariate Cox regression analysis, clinical endpoints were significantly associated with Geriatric Nutritional Risk Index (hazard ratio: 0.953, 95% confidence interval: 0.918–0.990), Prognostic Nutritional Index (hazard ratio: 0.942, 95% confidence interval: 0.892–0.996), and Controlling Nutritional Status score (hazard ratio: 1.230, 95% confidence interval: 1.056–1.433) after adjustment for factors associated in univariate Cox regression analysis. Malnutrition at diagnosis is a useful prognostic predictor for patients with pulmonary arterial hypertension. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2047-4873 28 18 2021 Incremental prognostic value of non-alcoholic fatty liver disease over coronary computed tomography angiography findings in patients with suspected coronary artery disease 2059 2066 EN Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Osawa Department of General Internal Medicine 3, Kawasaki Medical School General Medical Center Takashi Miki Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hironobu Toda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Science Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims　This study aimed to investigate additional risk stratification benefits of hepatic steatosis (HS) concurrently assessed during coronary computed tomography angiography (CTA) in a large patient cohort with suspected stable coronary artery disease (CAD). Methods and results　In this prospective study, 1148 Japanese outpatients without a history of CAD who underwent coronary CTA for suspected stable CAD (mean age 64 ± 14 years) were included. HS, defined on CT as a hepatic-to-spleen attenuation ratio of <1.0, was examined just before the evaluation of adverse CTA findings, defined as obstructive and/or high-risk plaque. The major adverse cardiac events (MACE) were the composite of cardiac death, acute coronary syndrome, and late revascularization. The incremental predictive value of HS was evaluated using the global χ2 test and C-statistic. HS was identified in 247 (22%) patients. During a median follow-up of 3.9 years, MACE was observed in 40 (3.5%) patients. HS was significantly associated with MACE in a model that included adverse CTA findings (hazard ratio 4.01, 95% confidence interval 2.12–7.59, P < 0.001). By adding HS to the Framingham risk score and adverse CTA findings, the global χ2 score and C-statistic significantly increased from 29.0 to 49.5 (P < 0.001) and 0.74 to 0.81 (P = 0.026), respectively. In subgroup analyses in patients with diabetes mellitus and metabolic syndrome, HS had significant additive predictive value for MACE over the Framingham risk score and adverse CTA findings. Conclusion　In patients with suspected stable CAD, concurrent evaluation of HS during coronary CTA enables more accurate detection of patients at higher risk of MACE. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2047-9980 12 10 2023 Significant Delayed Activation on the Right Ventricular Outflow Tract Represents Complete Right Bundle-Branch Block Pattern in Brugada Syndrome e028706 EN Yoshimasa Morimoto Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Hiroshi Morita Department of Cardiovascular Therapeutics , Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Tomofumi Mizuno Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Takuro Masuda Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Akira Ueoka Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Saori Asada Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Masakazu Miyamoto Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Satoshi Kawada Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Nobuhiro Nishii Department of Cardiovascular Therapeutics , Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine ,Okayama University Graduate School of Medicine, Dentistry, Pharmaceutical Sciences Background: The appearance of complete right bundle-branch block (CRBBB) in Brugada syndrome (BrS) is associated with an increased risk of ventricular fibrillation. The pathophysiological mechanism of CRBBB in patients with BrS has not been well established. We aimed to clarify the significance of a conduction delay zone associated with arrhythmias on CRBBB using body surface mapping in patients with BrS. Methods and Results: Body surface mapping was recorded in 11 patients with BrS and 8 control patients both with CRBBB. CRBBB in control patients was transiently exhibited by unintentional catheter manipulation (proximal RBBB). Ventricular activation time maps were constructed for both of the groups. We divided the anterior chest into 4 areas (inferolateral right ventricle [RV], RV outflow tract [RVOT], intraventricular septum, and left ventricle) and compared activation patterns between the 2 groups. Excitation propagated to the RV from the left ventricle through the intraventricular septum with activation delay in the entire RV in the control group (proximal RBBB pattern). In 7 patients with BrS, excitation propagated from the inferolateral RV to the RVOT with significant regional activation delay. The remaining 4 patients with BrS showed a proximal RBBB pattern with the RVOT activation delay. The ventricular activation time in the inferolateral RV was significantly shorter in patients with BrS without a proximal RBBB pattern than in control patients. Conclusions: The CRBBB morphology in patients with BrS consisted of 2 mechanisms: (1) significantly delayed conduction in the RVOT and (2) proximal RBBB with RVOT conduction delay. Significant RVOT conduction delay without proximal RBBB resulted in CRBBB morphology in patients with BrS. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 12 1 2022 Effects of luseogliflozin and voglibose on high-risk lipid profiles and inflammatory markers in diabetes patients with heart failure 15449 EN Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hajime Kihara Department of Internal Medicine, Kihara Cardiovascular Clinic Yoshiki Hata Department of Cardiology, Minamino Cardiovascular Hospital Toshihiko Nagano Department of Internal Medicine, Iwasa Hospital Atsushi Takaishi Department of Cardiology, Mitoyo General Hospital Hironobu Toda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Namba Department of Cardiology, Okayama Rosai Hospital Yoichi Nakamura Department of Cardiovascular Medicine, Specifed Clinic of Soyokaze Cardiovascular Medicine and Diabetes Care Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Sakuragi Department of Cardiovascular Medicine, Iwakuni Clinical Center Taro Minagawa Department of Internal Medicine, Minagawa Cardiovascular Clinic Yusuke Kawai Department of Cardiovascular Medicine, Okayama City Hospital Nobuhiro Nishii Department of Internal Medicine, Yoshinaga Hospital Soichiro Fuke Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital Masaki Yoshikawa Department of Cardiology, Fukuyama City Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The MUSCAT-HF Study Investigators Sodium-glucose cotransporter 2 inhibitors could reduce cardiovascular events in patients with heart failure irrespective of diabetes status. In this prespecified sub-analysis of randomised-controlled trial, we investigated the efficacy of luseogliflozin (2.5 mg daily), a sodium-glucose cotransporter 2 inhibitor, with that of voglibose (0.6 mg daily), an alpha-glucosidase inhibitor, on high-risk lipid profile and inflammatory markers in patients with type-2 diabetes and heart failure. Among the 157 patients studied, there were no significant differences in the mean malondialdehyde LDL or small-dense LDL cholesterol levels between the luseogliflozin and voglibose groups (percent change: 0.2% vs. - 0.6%, p = 0.93; - 1.7% vs. - 8.6%, p= 0.21) after 12 weeks in comparison to levels at the baseline. No significant difference was observed between the two groups in the adiponectin and high-sensitivity C-reactive protein levels after 12 weeks compared to the baseline levels (percent change, - 1.6% vs. - 4.0% and 22.5% vs. 10.0%; p = 0.52 and p = 0.55, respectively). In conclusion, in patients with type-2 diabetes and heart failure, compared to voglibose, luseogliflozin did not significantly improve the high-risk lipoprotein profile including malondialdehyde LDL and small-dense LDL cholesterol or the levels of inflammatory markers, including adiponectin and high-sensitivity C-reactive protein. No potential conflict of interest relevant to this article was reported.

Wiley Periodicals, Inc Acta Medica Okayama 2055-5822 2022 Differences in extracellular fluid volume between acute heart failure patients with and without high systolic blood pressure EN Yusuke Namba Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Yunoki Department of Cardiovascular Medicine, Tsuyama Chuo Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takefumi Oka Department of Cardiovascular Medicine, Tsuyama Chuo Hospital Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims Some reports have suggested that hypertensive acute heart failure (AHF) is caused by intravascular congestion, not interstitial congestion. We evaluated the differences in extracellular fluid volume assessed by bioelectrical impedance analysis (BIA) between AHF patients with and without high systolic blood pressure (sBP). Methods This prospective single-centre study (UMIN000030266) included 178 patients hospitalized due to AHF between September 2017 and August 2018. We calculated extracellular water (ECW), intracellular water (ICW), total body water (TBW), and ECW-to-TBW ratio (oedema index: EI) by BIA and evaluated conventional parameters as follows: weight, N-terminal pro brain natriuretic peptide values, and echocardiography parameters on admission and before discharge. One-year outcomes included all-cause death and re-admission due to heart failure. We compared patients with sBP > 140 mmHg on admission [clinical scenario 1 (CS1) group] and with sBP of <= 140 mmHg on admission (non-CS1 group). Results The mean age of the patients was 79.5 +/- 11.1 years, and 48.9% of the patients were female. EI on admission of 83 patients in the CS1 group was lower than that of 95 patients in the non-CS1 group. The change in EI from admission to before discharge was no significant in the CS1 group but was significant in the non-CS1 group. Comparing the changes from admission to before discharge between the CS1 and the non-CS1 group, delta ECW, delta ICW, delta TBW, and delta EI of the CS1 group were significantly smaller than those of the non-CS1 group. During the 1-year follow-up period after discharge of the 178 patients, the numbers of deaths and re-admissions due to acute HF were 26 (15%) and 49 (28%), respectively. Patients with high EI before discharge [> 0.408 (median)] had significantly more cardiac events than patients with low EI [hazard ratio (HR): 2.15, 95% confidence interval (CI): 1.30-3.55]. Cox regression analysis revealed that higher EI as a continuous variable was significantly associated with worse outcome in non-CS1 group (HR: 1.46, 95% CI: 1.13-1.87), but not significantly associated with worse outcome in CS1 group (HR: 1.29, 95% CI: 0.98-1.69). Conclusions EI on admission in patients with high sBP was not elevated, and changes in ECW, ICW, TBW, and EI in patients with high sBP were smaller than those in patients without high sBP. EI measured by BIA could distinguish AHF with interstitial or intravascular congestion. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2075-1729 12 5 2022 Quantification of Lung Perfusion Blood Volume in Dual-Energy Computed Tomography in Patients with Pulmonary Hypertension 684 EN Satoko Ugawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Dual-energy computed tomography (DECT) is a promising technique for the assessment of the lung perfused blood volume (LPBV) in the lung parenchyma. This study was performed to compare the LPBV by DECT of patients with pulmonary hypertension (PH) and controls and to evaluate the association between the LPBV and the perfusion ratio derived by lung perfusion scintigraphy. This study involved 45 patients who underwent DECT (25 patients with PH and 20 controls). We measured the total LPBV and distribution of the LPBV in each lung. The total LPBV was significantly lower in the PH group than the control group (38 +/- 9 vs. 45 +/- 8 HU, p = 0.024). Significant differences were observed between the LPBV of the upper lung of the PH and control groups (34 +/- 10 vs. 47 +/- 10, p = 0.021 and 37 +/- 10 vs. 47 +/- 8, p < 0.001). A significant correlation was observed between the LPBV and the lung perfusion scintigraphy. A lower total LPBV and lower LPBV of the upper lung as detected by DECT might be specific findings of PH. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 23 7 2022 Pathophysiology and Treatment of Diabetic Cardiomyopathy and Heart Failure in Patients with Diabetes Mellitus 3587 EN Kazufumi Nakamura Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Miyoshi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masashi Yoshida Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Akagi Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yukihiro Saito Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Ejiri Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoaki Matsuo Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keishi Ichikawa Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Keiichiro Iwasaki Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Naito Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Namba Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masatoki Yoshida Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroki Sugiyama Department of Internal Medicine, Okayama Saiseikai General Hospital Hiroshi Ito Department of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University There is a close relationship between diabetes mellitus and heart failure, and diabetes is an independent risk factor for heart failure. Diabetes and heart failure are linked by not only the complication of ischemic heart disease, but also by metabolic disorders such as glucose toxicity and lipotoxicity based on insulin resistance. Cardiac dysfunction in the absence of coronary artery disease, hypertension, and valvular disease is called diabetic cardiomyopathy. Diabetes-induced hyperglycemia and hyperinsulinemia lead to capillary damage, myocardial fibrosis, and myocardial hypertrophy with mitochondrial dysfunction. Lipotoxicity with extensive fat deposits or lipid droplets is observed on cardiomyocytes. Furthermore, increased oxidative stress and inflammation cause cardiac fibrosis and hypertrophy. Treatment with a sodium glucose cotransporter 2 (SGLT2) inhibitor is currently one of the most effective treatments for heart failure associated with diabetes. However, an effective treatment for lipotoxicity of the myocardium has not yet been established, and the establishment of an effective treatment is needed in the future. This review provides an overview of heart failure in diabetic patients for the clinical practice of clinicians. No potential conflict of interest relevant to this article was reported.

Wiley Periodicals, Inc Acta Medica Okayama 2055-5822 2021 Effects of luseogliflozin on estimated plasma volume in patients with heart failure with preserved ejection fraction EN Mitsutaka Nakashima Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hajime Kihara Department of Internal Medicine, Kihara Cardiovascular Clinic Yoshiki Hata Department of Cardiology, Minamino Cardiovascular Hospital Toshihiko Nagano Department of Internal Medicine, Iwasa Hospital, Atsushi Takaishi Department of Cardiology, Mitoyo General Hospital Hironobu Toda Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Seiji Nanba Department of Cardiology, Okayama Rosai Hospital Yoichi Nakamura Department of Cardiovascular Medicine, Specified Clinic of Soyokaze CardioVascular Medicine and Diabetes Care, Matsuyama Satoshi Akagi Department of Internal Medicine, Akaiwa Medical Association Hospital Satoru Sakuragi Department of Cardiovascular Medicine, Iwakuni Clinical Center Taro Minagawa Department of Internal Medicine, Minagawa Cardiovascular Clinic Yusuke Kawai Department of Cardiovascular Medicine, Okayama City Hospital Nobuhiro Nishii Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Fuke Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital Masaki Yoshikawa Department of Cardiology, Fukuyama City Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences MUSCAT-HF Study Investigators Aims Sodium glucose co-transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). Methods and results This study was a post-hoc analysis of the MUSCAT-HF trial (UMIN000018395), a multicentre, prospective, open-label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed-effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group-difference -6.43% [95% confidence interval (CI): -9.11 to -3.74]}, at Week 12 [-8.73% (95%CI: -11.40 to -6.05)], and at Week 24 [-11.02% (95%CI: -13.71 to -8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log-transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019). Conclusions Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 09145087 78 1 2020 Inhibitory effects of RAGE-aptamer on development of monocrotaline-induced pulmonary arterial hypertension in rats 12 16 EN Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masakiyo Sakaguchi Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naofumi Amioka Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Luh Oliva Saraswati Suastika Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Megumi Kondo Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Rie Nakayama Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuichiro Higashimoto Department of Chemistry, Kurume University School of Medicine Kei Fukami Division of Nephrology, Department of Medicine, Kurume University School of Medicine Hiromi Matsubara Department of Cardiology, National Hospital Organization Okayama Medical Center Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: The receptor for advanced glycation end products (RAGE), a transmembrane receptor belonging to the immunoglobulin superfamily, is overexpressed in pulmonary artery smooth muscle cells (PASMCs) in patients with pulmonary arterial hypertension (PAH) and is implicated in the etiology of PAH. Recently, we reported that RAGE-aptamer, a short and single-stranded DNA directed against RAGE, inhibited an inappropriate increase in cultured PASMCs in PAH. The aim of this study was to determine the efficacy of RAGEaptamer in monocrotaline-induced PAH in rats. Methods and Results: Rats were assigned to either an untreated control group, a group that received continuous subcutaneous administration of RAGE-aptamer immediately after monocrotaline injection, or a group that received control-aptamer immediately after monocrotaline injection. All rats survived 21 days after injection of monocrotaline and control-aptamer or RAGE-aptamer. Injection of monocrotaline with continuous subcutaneous delivery of control-aptamer resulted in higher right ventricular systolic pressure compared with controls. This increase was attenuated by continuous subcutaneous delivery of RAGE-aptamer. The proportion of small pulmonary arteries with full muscularization was greater in the monocrotaline and control-aptamer group than in the control group. Continuous subcutaneous delivery of RAGE-aptamer significantly reduced the percentage of small pulmonary arteries with full muscularization Conclusions: Continuous subcutaneous delivery of RAGE-aptamer suppresses development of monocrotaline-induced PAH in rats. Inhibition of RAGE ameliorates muscularization of 3 small pulmonary arteries. Treatment with RAGE-aptamer might be a new therapeutic option for PAH. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 2045-8932 9 1 2019 Improvement of lung function and pulmonary hypertension after pulmonary aneurysm repair: case series 2045894019831217 EN Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Hospital Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Pulmonary artery aneurysms (PAA) can be complicated with pulmonary arterial hypertension (PAH), causing sudden death due to PA rupture and dissection. Because treatment with PAH-targeted drugs does not always prevent PAA progression, prophylactic surgical repair of the PAA seems a promising alternative. However, although it avoids rupture and dissection of the PAs, additional benefits have not been forthcoming. We therefore present two patients with co-existing PAH and a PAA who underwent surgical repair of the aneurysm. Following the surgery, their lung function and pulmonary hypertension improved. Optimal treatment of PAA remains uncertain, however, with no clear guidelines regarding the best therapeutic approach. This case series provides physicians with reasons to repair PAA surgically in patients with PAH. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 75 1 2021 Possible Protective Effect of Remote Ischemic Preconditioning on Acute Kidney Injury Following Elective Percutaneous Coronary Intervention: Secondary Analysis of a Multicenter, Randomized Study 45 53 EN Hiroaki Otsuka Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Kunihisa Kohno Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Makoto Nakahama Department of Cardiology, Fukuyama City Hospital Masayuki Doi Department of Cardiology, Kagawa Prefectural Central Hospital Mitsuru Munemasa Department of Cardiology, Okayama Medical Center Masaaki Murakami Department of Cardiology, Okayama Heart Clinic Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Original Article 10.18926/AMO/61433 Remote ischemic preconditioning (RIPC) is a promising strategy for protecting against ischemic reperfusion injury. This study is a secondary analysis of a randomized study that aimed to evaluate the effect of RIPC on the early increase in serum creatinine (SCr) following percutaneous coronary intervention (PCI), which is associ-ated with contrast-induced acute kidney injury. Patients with stable angina undergoing elective PCI were assigned to control, RIPC, and continuous infusion of nicorandil (nicorandil) groups. The endpoint of this study was the incidence of the early increase in SCr, a predictor of contrast-induced acute kidney injury, which was defined as either a > 20% or absolute increase by 0.3 mg/dl of SCr levels after 24 h of PCI. This study included 220 patients for whom a dataset of SCr values was available. The incidence of the early increase in SCr was significantly lower in the RIPC than in the control (1.3% vs 10.8%, p = 0.03) group, but was not significantly different between the nicorandil and control groups. In multivariate analysis, RIPC remained a significant fac-tor associated with a reduction in the incidence of early increase in SCr. RIPC reduces the incidence of early increase in SCr in patients with stable angina following elective PCI. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1475-2840 20 1 2021 Prognostic value of non-alcoholic fatty liver disease for predicting cardiovascular events in patients with diabetes mellitus with suspected coronary artery disease: a prospective cohort study 2021 EN Keishi Ichikawa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Toru Miyoshi Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuhiro Osawa Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Takashi Miki Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hironobu Toda Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kentaro Ejiri Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masatoki Yoshida Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yusuke Nanba Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Masashi Yoshida Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazufumi Nakamura Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroshi Morita Department of Cardiovascular Therapeutics, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hiroshi Ito Department of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background Risk stratification of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) has not been established. Coronary artery calcium score (CACS) and non-alcoholic fatty liver disease (NAFLD) are independently associated with cardiovascular events in T2DM patients. This study examined the incremental prognostic value of NAFLD assessed by non-enhanced computed tomography (CT) in addition to CACS and Framingham risk score (FRS) for cardiovascular events in T2DM patients. Methods This prospective pilot study included 529 T2DM outpatients with no history of cardiovascular disease who underwent CACS measurement because of suspected coronary artery disease. NAFLD was defined on CT images as a liver:spleen attenuation ratio < 1.0. Cardiovascular events were defined as cardiovascular death, nonfatal myocardial infarction, late coronary revascularization, nonfatal stroke, or hospitalization for heart failure. Results Among 529 patients (61% men, mean age 65 years), NAFLD was identified in 143 (27%). Forty-four cardiovascular events were documented during a median follow-up of 4.4 years. In multivariate Cox regression analysis, NAFLD, CACS, and FRS were associated with cardiovascular events (hazard ratios and 95% confidence intervals 5.43, 2.82–10.44, p < 0.001; 1.56, 1.32–1.86, p < 0.001; 1.23, 1.08–1.39, p = 0.001, respectively). The global χ2 score for predicting cardiovascular events increased significantly from 27.0 to 49.7 by adding NAFLD to CACS and FRS (p < 0.001). The addition of NAFLD to a model including CACS and FRS significantly increased the C-statistic from 0.71 to 0.80 (p = 0.005). The net reclassification achieved by adding CACS and FRS was 0.551 (p < 0.001). Conclusions NAFLD assessed by CT, in addition to CACS and FRS, could be useful for identifying T2DM patients at higher risk of cardiovascular events. No potential conflict of interest relevant to this article was reported.

The Japanese Circulation Society Acta Medica Okayama 1346-9843 84 2 2020 Marked Reduction of Pulmonary Artery Pressure After Registration for Lung Transplantation Is Associated With Long-Term Survival in Patients With Pulmonary Arterial Hypertension　― Cohort Study ― 245 251 EN Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hiromi Matsubara Division of Cardiology, Okayama Medical Center Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Takahiro Oto Department of Organ Transplant Center, Okayama University Hospital Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science Background:The waiting period for lung transplantation (LT) is approximately 3 years in Japan. The prognosis of patients with pulmonary arterial hypertension (PAH) awaiting LT is poor without LT. Patients at the present center often survive in the long term after registration for LT. The aim of this study was to elucidate why some patients survive in the long term by investigating changes in pulmonary artery pressure (PAP) after registration, and medication used. Methods and Results:This study involved 57 patients with PAH who were enrolled in a registry for LT at Okayama University Hospital. We divided patients into 3 groups according to outcome: LT (n=27); death without LT (n=21); and survival without LT (n=9). The median interval from PAH diagnosis to epoprostenol treatment was shorter in the survival group (58 days) than in the LT group (378 days) and death group (545 days). Eight patients in the survival group, 13 in the LT group, and 13 in the death group underwent right heart catheterization after registration. Percent change in mean PAP after registration was significantly greater in the survival group (－32%) than in the LT group (－13%) and death group (1%; P<0.01). Conclusions:Even after LT registration, patients who received epoprostenol infusion soon after diagnosis of PAH often had marked reduction in PAP and long-term survival without LT. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2047-9980 9 16 2020 Effect of Luseogliflozin on Heart Failure With Preserved Ejection Fraction in Patients With Diabetes Mellitus e015103 EN Kentaro Ejiri Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Toru Miyoshi Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Hajime Kihara Department of Internal Medicine, Kihara Cardiovascular Clinic Yoshiki Hata Department of Cardiology, Minamino Cardiovascular Hospital Toshihiko Nagano Department of Internal Medicine, Iwasa Hospital Atsushi Takaishi Department of Cardiology, Mitoyo General Hospital Hironobu Toda Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Seiji Nanba Department of Cardiology, Okayama Rosai Hospital Yoichi Nakamura Department of Cardiovascular Medicine, Specified Clinic of Soyokaze Cardiovascular Medicine and Diabetes Care Satoshi Akagi Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Satoru Sakuragi Department of Cardiovascular Medicine, Iwakuni Clinical Center Taro Minagawa Department of Internal Medicine, Minagawa Cardiovascular Clinic Yusuke Kawai Department of Cardiovascular Medicine, Okayama City Hospital Nobuhiro Nishii Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Soichiro Fuke Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital Masaki Yoshikawa Department of Cardiology, Fukuyama City Hospital Kazufumi Nakamura Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Hiroshi Ito Okayama University Graduate School of Medicine, Density and Pharmaceutical Sciences Background Effects of sodium‐glucose cotransporter 2 inhibitors on reducing hospitalization for heart failure have been reported in randomized controlled trials, but their effects on patients with heart failure with preserved ejection fraction (HFpEF) are unknown. This study aimed to evaluate the drug efficacy of luseogliflozin, a sodium‐glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus and HFpEF. Methods and Results We performed a multicenter, open‐label, randomized, controlled trial for comparing luseogliflozin 2.5 mg once daily with voglibose 0.2 mg 3 times daily in patients with type 2 diabetes mellitus suffering from HFpEF (left ventricular ejection fraction >45% and BNP [B‐type natriuretic peptide] concentrations ≥35 pg/mL) in a 1:1 randomization fashion. The primary outcome was the difference from baseline in BNP levels after 12 weeks of treatment between the 2 drugs. A total of 173 patients with diabetes mellitus and HFpEF were included. Of these, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in BNP concentrations after 12 weeks from baseline between the 2 groups. The ratio of the mean BNP value at week 12 to the baseline value was 0.79 in the luseogliflozin group and 0.87 in the voglibose group (percent change, －9.0% versus －1.9%; ratio of change with luseogliflozin versus voglibose, 0.93; 95% CI, 0.78–1.10; P=0.26). Conclusion In patients with type 2 diabetes mellitus and HFpEF, there is no significant difference in the degree of reduction in BNP concentrations after 12 weeks between luseogliflozin and voglibose. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 20 23 2019 Current Treatment Strategies and Nanoparticle-Mediated Drug Delivery Systems for Pulmonary Arterial Hypertension 5885 EN Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Ejiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masashi Yoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihisa Toh Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koji Nakagawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Takaya Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromi Matsubara Division of Cardiology, National Hospital Organization Okayama Medical Center Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences There are three critical pathways for the pathogenesis and progression of pulmonary arterial hypertension (PAH): the prostacyclin (prostaglandin I-2) (PGI(2)), nitric oxide (NO), and endothelin pathways. The current approved drugs targeting these three pathways, including prostacyclin (PGI(2)), phosphodiesterase type-5 (PDE5) inhibitors, and endothelin receptor antagonists (ERAs), have been shown to be effective, however, PAH remains a severe clinical condition and the long-term survival of patients with PAH is still suboptimal. The full therapeutic abilities of available drugs are reduced by medication, patient non-compliance, and side effects. Nanoparticles are expected to address these problems by providing a novel drug delivery approach for the treatment of PAH. Drug-loaded nanoparticles for local delivery can optimize the efficacy and minimize the adverse effects of drugs. Prostacyclin (PGI(2)) analogue, PDE5 inhibitors, ERA, pitavastatin, imatinib, rapamycin, fasudil, and oligonucleotides-loaded nanoparticles have been reported to be effective in animal PAH models and in vitro studies. However, the efficacy and safety of nanoparticle mediated-drug delivery systems for PAH treatment in humans are unknown and further clinical studies are required to clarify these points. No potential conflict of interest relevant to this article was reported.

SAGE Publications Inc Acta Medica Okayama 2045-8932 9 4 2019 Liver transplantation in a patient with hereditary haemorrhagic telangiectasia and pulmonary hypertension EN Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Akagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazufumi Nakamura Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naofumi Amioka Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keishi Ichikawa Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takahito Yagi Department of Hepato-Biliary-Pancreatic Surgery, Okayama University Hospital Hiroshi Ito Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hereditary haemorrhagic telangiectasia or Rendu-Osler-Weber syndrome is a systemic vascular disease with autosomal dominant inheritance, mucocutaneous telangiectasia, and repeated nasal bleeding due to vascular abnormalities. Hereditary haemorrhagic telangiectasia may occasionally lead to complications, including arteriovenous malformations and pulmonary hypertension. We present a case of a 52-year-old female patient with hereditary haemorrhagic telangiectasia who was referred to our hospital for treatment of pulmonary hypertension. She had been diagnosed with hereditary haemorrhagic telangiectasia during adolescence and was being followed up. Six months prior to presentation, she had undergone coil embolization for pulmonary haemorrhage due to pulmonary arteriovenous malformations. She was in World Health Organization functional class IV, with a mean of pulmonary arterial pressure of 38 mmHg, a pulmonary capillary wedge pressure of 10 mmHg, and a right atrial pressure of 22 mmHg. A contrast-enhanced computed tomography angiography showed large arteriovenous malformations in the liver. Right heart catheterization revealed an increase in oxygen saturation in the inferior vena cava between the supra- and infra-hepatic veins, low pulmonary vascular resistance, and high right atrial pressure. Hence, she was diagnosed with hereditary haemorrhagic telangiectasia with pulmonary hypertension due to major arteriovenous shunt resulting from arteriovenous malformations in the liver. Therefore, we considered liver transplantation as an essential treatment option. She underwent cadaveric liver transplantation after a year resulting in dramatic haemodynamic improvement to World Health Organization functional class I. Liver transplantation is a promising treatment in patients with hereditary haemorrhagic telangiectasia and pulmonary hypertension resulting from arteriovenous shunt caused by arteriovenous malformations in the liver. No potential conflict of interest relevant to this article was reported.