Okayama University Medical SchoolActa Medica Okayama0386-300X7512021Possible Protective Effect of Remote Ischemic Preconditioning on Acute Kidney Injury Following Elective Percutaneous Coronary Intervention: Secondary Analysis of a Multicenter, Randomized Study4553ENHiroakiOtsukaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical SciencesKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical SciencesKunihisaKohnoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical SciencesMakotoNakahamaDepartment of Cardiology, Fukuyama City HospitalMasayukiDoiDepartment of Cardiology, Kagawa Prefectural Central HospitalMitsuruMunemasaDepartment of Cardiology, Okayama Medical CenterMasaakiMurakamiDepartment of Cardiology, Okayama Heart ClinicKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical SciencesOriginal Article10.18926/AMO/61433Remote 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.RwActa Medica Okayama0030-155812432012z펾ɂRÌŁERÖ@253254ENToruMiyoshiNo potential conflict of interest relevant to this article was reported.Wiley-BlackwellActa Medica Okayama1347-9032103102012Tumor growth inhibitory effect of ADAMTS1 is accompanied by the inhibition of tumor angiogenesis18891897ENMasanariObikaHirokoOgawaKatsuyukiTakahashiJiayiLiOmer FarukHatipogluMehmet ZeynelCilekToruMiyoshiJunkoInagakiTakashiOhtsukiShozoKusachiYoshifumiNinomiyaSatoshiHirohataAngiogenesis plays an important role in tumor progression. Several reports have demonstrated that a disintegrin and metalloproteinase with thrombospondin motifs1 (ADAMTS1) inhibited angiogenesis via multiple mechanisms. The aim of this study was to investigate the effect of ADAMTS1 on endothelial cells in vitro and on tumor growth with regard to angiogenesis in vivo. We examined the effects of the transfection of ADAMTS1 using two constructs, full-length ADAMTS1 (full ADAMTS1) and catalytic domain-deleted ADAMTS1 (delta ADAMTS1). Transfection of both the full ADAMTS1 and delta ADAMTS1 gene constructs demonstrated the secretion of tagged-ADAMTS1 protein into the conditioned medium, so we examined the effects of ADAMTS1-containing conditioned medium on endothelial cells. Both types of conditioned media inhibited endothelial tube formation, and this effect was completely abolished after immunoprecipitation of the secreted protein from the medium. Both types of conditioned media also inhibited endothelial cell migration and proliferation. We then examined the impact of ADAMTS1 on endothelial cell apoptosis. Both conditioned media increased the number of Annexin V-positive endothelial cells and caspase-3 activity and this effect was attenuated when z-vad was added. These results indicated that ADAMTS1 induced endothelial cell apoptosis. We next examined the effects of ADAMTS1 gene transfer into tumor-bearing mice. Both full ADAMTS1 and delta ADAMTS1 significantly inhibited the subcutaneous tumor growth. Collectively, our results demonstrated that ADAMTS1 gene transfer inhibited angiogenesis in vitro and in vivo, likely as a result of the induction of endothelial cell apoptosis by ADAMTS1 that occurs independent of the protease activity.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1942013Serum cystatin C as a biomarker of cardiac diastolic dysfunction in patients with cardiac disease and preserved ejection fractionE35E39ENKazumasaNosakaKazufumiNakamuraKengoKusanoNorihisaTohTakeshiTadaToruMiyoshiMasayukiDoiKunihisaKohnoHiroshiMoritaHiroshiItoDiastolic dysfunction of the heart is correlated with cardiac mortality. Serum cystatin C (CysC) is an endogenous marker of kidney function. It is not clear whether serum CysC is associated with diastolic dysfunction in patients with varying cardiac conditions with concomitant diastolic abnormalities and preserved ejection fraction (EF). The authors measured serum CysC levels in patients with cardiac diseases and examined the relationships between serum CysC levels and diastolic function. Serum CysC was measured and echocardiography was performed in 124 consecutive patients with cardiac diseases. Transmitral flow (TMF) patterns surrogating diastolic function were categorized into two groups: a normal group and an abnormal group. Serum CysC and BNP showed a significant positive correlation. There were no significant differences in serum CysC among those cardiac diseases. Seventy-eight patients with cardiac disease and preserved EF (left ventricular EF ≥50%) and without renal dysfunction (estimated glomerular filtration rate ≥60 mL/minute/1.73 m(2) ) were examined. Multivariate linear regression analysis demonstrated that left atrium diameter and abnormal TMF patterns were independent determinants of serum CysC. Furthermore, patients with elevated serum CysC levels had poor prognosis. Serum CysC is associated with diastolic dysfunction in patients with various cardiac diseases and preserved EF. Serum CysC might be a biomarker of cardiac diastolic dysfunction in patients with preserved EF.No potential conflict of interest relevant to this article was reported.Acta Medica Okayama1346-98437692012Impact of Chronic Kidney Disease on Left Main Coronary Artery Disease and Prognosis in Japanese Patients22662272ENKazuhiroDanToruMiyoshiMasayukiUeedaHiroakiOhtsukaSatokoUgawaNobuhikoOhnishiAtsushiTakaishiKazufumiNakamuraKengoKusanoHiroshiItoBackground: Renal insufficiency plays a critical role in the pathogenesis of ischemic heart disease. The aim of the present study was to investigate the prevalence of renal dysfunction and its impact on prognosis in patients with left main coronary artery disease (LMCAD) and stable angina pectoris.
Methods and Results: A total of 626 consecutive patients with significant coronary artery stenosis were enrolled. Renal insufficiency was graded using estimated glomerular filtration rate (eGFR) before coronary angiography. Chronic kidney disease (CKD) was defined as eGFR <60 ml.min(-1) 1.73 m(-2) and/or proteinuria. Patients with LMCAD (n=95) had a significantly higher prevalence of CKD than those without LMCAD (P=0.02). Multiple logistic regression analysis showed that CKD was independently associated with LMCAD (adjusted odds ratio, 1.74; 95% confidence interval [CI]: 1.09-2.76, P=0.01). A 1-year follow-up of patients with LMCAD showed that the cumulative incidence of major adverse cardiovascular events among patients with eGFR <30 ml.min(-1).1.73 m(-2) was higher than that among patients with eGFR >= 60 ml.min(-1).1.73 m(-2) (P=0.03). The hazard ratio for a cardiovascular event was 9.54 (95% CI: 3.15-28.89, P<0.01) when comparing patients with LMCAD and eGFR <30 ml.min(-1).1.73 m(-2) vs. patients without LMCAD and eGFR >= 60 ml.min(-1).1.73 m(-2).
Conclusions: Renal insufficiency is a risk factor for LMCAD and predicts poor prognosis in Japanese patients.No potential conflict of interest relevant to this article was reported.Nature Publishing GroupActa Medica Okayama0916-9636424252019The optimal amount of salt intake.752753ENKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, OkayamaToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, OkayamaNo potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-006720232019Current Treatment Strategies and Nanoparticle-Mediated Drug Delivery Systems for Pulmonary Arterial Hypertension5885ENKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiAkagi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroEjiri Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshida Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshi Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNorihisaTohDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiNakagawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiromiMatsubaraDivision of Cardiology, National Hospital Organization Okayama Medical CenterHiroshiIto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThere 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.The Japanese Circulation SocietyActa Medica Okayama1346-98438432020New Appearance of Fragmented QRS as a Predictor of Ventricular Arrhythmic Events in Patients With Hypertrophic Cardiomyopathy487ENSoichiroOguraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMoritaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNorihisaTohDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiNakagawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsuyukiWatanabeDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhiroNishiiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Multiple spikes in the QRS complex (fragmented QRS [fQRS]) on 12-lead electrocardiography have been associated with ventricular arrhythmic events (VAEs) in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to assess the association between new appearances of fQRS and cardiac events in patients with HCM.Methods and Results:The association between baseline fQRS and cardiac events, namely VAEs, heart failure-related hospitalization, and all-cause death, was evaluated retrospectively in 146 HCM patients (46 patients with fQRS, 100 without fQRS). The median follow-up was 5.3 years. Cardiac events occurred in 29 patients with baseline fQRS and 32 patients without baseline fQRS (63% vs. 32%; P<0.001). VAEs occurred in a significantly larger percentage of patients with than without baseline fQRS (54% vs. 23%, respectively; P<0.001). Of the 100 patients without baseline fQRS, 33 had a new appearance of fQRS during the 4.6-year follow-up, whereas 67 did not. VAEs occurred more frequently in the 33 patients with the appearance of fQRS than in those without (42% vs. 13%, respectively; P=0.001). Multivariable analysis showed that the new appearance of fQRS documented before VAEs was associated with VAEs (hazard ratio 4.29, 95% confidence interval 1.81-10.2; P=0.001).<br/>
Conclusions: The new appearance of fQRS was associated with an increased risk of VAEs in HCM patients.No potential conflict of interest relevant to this article was reported.NatureActa Medica Okayama2045-23221012020Deficiency of CD44 prevents thoracic aortic dissection in a murine model6869ENOmer F.HatipogluDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceTomokoYonezawaDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceNaofumiAmiokaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceSatoshiHirohataDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceThoracic aortic dissection (TAD) is a life-threatening vascular disease. We showed that CD44, a widely distributed cell surface adhesion molecule, has an important role in inflammation. In this study, we examined the role of CD44 in the development of TAD. TAD was induced by the continuous infusion of beta-aminopropionitrile (BAPN), a lysyl oxidase inhibitor, and angiotensin II (AngII) for 7 days in wild type (WT) mice and CD44 deficient (CD44(-/-)) mice. The incidence of TAD in CD44(-/-) mice was significantly reduced compared with WT mice (44% and 6%, p<0.01). Next, to evaluate the initial changes, aortic tissues at 24hours after BAPN/AngII infusion were examined. Neutrophil accumulation into thoracic aortic adventitia in CD44(-/-) mice was significantly decreased compared with that in WT mice (5.7 +/- 0.3% and 1.6 +/- 0.4%, p<0.01). In addition, BAPN/AngII induced interleukin-6, interleukin-1 beta, matrix metalloproteinase-2 and matrix metalloproteinase-9 in WT mice, all of which were significantly reduced in CD44(-/-) mice (all p<0.01). In vitro transmigration of neutrophils from CD44(-/-) mice through an endothelial monolayer was significantly decreased by 18% compared with WT mice (p<0.01). Our findings indicate that CD44 has a critical role in TAD development in association with neutrophil infiltration into adventitia.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1475-28401912020Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet149ENMasatokiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKaoruAkazawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomonariKimuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroakiOhtsukaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoOhnoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaijiMiuraDepartment of Basic and Clinical Medicine, Nagano College of NursingHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground Statins suppress the progression of atherosclerosis by reducing low-density lipoprotein (LDL) cholesterol levels. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor alpha modulator, is expected to reduce residual risk factors including high triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol during statin treatment. However, it is not known if statin therapy with add-on pemafibrate improves the progression of atherosclerosis. The aim of this study was to assess the effect of combination therapy with pitavastatin and pemafibrate on lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Methods Seven-week-old male Dahl salt-sensitive (DS) rats were divided into the following five treatment groups (normal diet (ND) plus vehicle, high-salt and high-fat diet (HD) plus vehicle, HD plus pitavastatin (0.3 mg/kg/day), HD plus pemafibrate (K-877) (0.5 mg/kg/day), and HD plus combination of pitavastatin and pemafibrate) and treated for 12 weeks. At 19 weeks, endothelium-dependent relaxation of the thoracic aorta in response to acetylcholine was evaluated. Results After feeding for 12 weeks, systolic blood pressure and plasma levels of total cholesterol were significantly higher in the HD-vehicle group compared with the ND-vehicle group. Combination therapy with pitavastatin and pemafibrate significantly reduced systolic blood pressure, TG levels, including total, chylomicron (CM), very LDL (VLDL), HDL-TG, and cholesterol levels, including total, CM, VLDL, and LDL-cholesterol, compared with vehicle treatment. Acetylcholine caused concentration-dependent relaxation of thoracic aorta rings that were pre-contracted with phenylephrine in all rats. Relaxation rates in the HD-vehicle group were significantly lower compared with the ND-vehicle group. Relaxation rates in the HD-combination of pitavastatin and pemafibrate group significantly increased compared with the HD-vehicle group, although neither medication alone ameliorated relaxation rates significantly. Western blotting experiments showed increased phosphorylated endothelial nitric oxide synthase protein expression in aortas from rats in the HD-pemafibrate group and the HD-combination group compared with the HD-vehicle group. However, the expression levels did not respond significantly to pitavastatin alone. Conclusions Combination therapy with pitavastatin and pemafibrate improved lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Pemafibrate as an add-on strategy to statins may be useful for preventing atherosclerosis progression.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2047-99809162020Effect of Luseogliflozin on Heart Failure With Preserved Ejection Fraction in Patients With Diabetes Mellituse015103ENKentaroEjiriOkayama University Graduate School of Medicine, Density and Pharmaceutical SciencesToruMiyoshiOkayama University Graduate School of Medicine, Density and Pharmaceutical SciencesHajimeKiharaDepartment of Internal Medicine, Kihara Cardiovascular ClinicYoshikiHataDepartment of Cardiology, Minamino Cardiovascular HospitalToshihikoNaganoDepartment of Internal Medicine, Iwasa HospitalAtsushiTakaishiDepartment of Cardiology, Mitoyo General HospitalHironobuTodaOkayama University Graduate School of Medicine, Density and Pharmaceutical SciencesSeijiNanbaDepartment of Cardiology, Okayama Rosai HospitalYoichiNakamuraDepartment of Cardiovascular Medicine, Specified Clinic of Soyokaze Cardiovascular Medicine and Diabetes CareSatoshiAkagiOkayama University Graduate School of Medicine, Density and Pharmaceutical SciencesSatoruSakuragiDepartment of Cardiovascular Medicine, Iwakuni Clinical CenterTaroMinagawaDepartment of Internal Medicine, Minagawa Cardiovascular ClinicYusukeKawaiDepartment of Cardiovascular Medicine, Okayama City HospitalNobuhiroNishiiOkayama University Graduate School of Medicine, Density and Pharmaceutical SciencesSoichiroFukeDepartment of Cardiovascular Medicine, Japanese Red Cross Okayama HospitalMasakiYoshikawaDepartment of Cardiology, Fukuyama City HospitalKazufumiNakamuraOkayama University Graduate School of Medicine, Density and Pharmaceutical SciencesHiroshiItoOkayama University Graduate School of Medicine, Density and Pharmaceutical SciencesBackground</br>
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.</br>
Methods and Results</br>
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).</br>
Conclusion</br>
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.BMCActa Medica Okayama1475-28401912020Correction to: Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl/salt-sensitive rats fed a high-salt and high-fat diet213ENMasatokiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKaoruAkazawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomonariKimuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroakiOhtsukaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoOhnoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDaijiMiuraDepartment of Basic and Clinical Medicine, Nagano College of NursingHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNo potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1475-28402012021Prognostic value of non-alcoholic fatty liver disease for predicting cardiovascular events in patients with diabetes mellitus with suspected coronary artery disease: a prospective cohort study2021ENKeishiIchikawaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToruMiyoshiDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKazuhiroOsawaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineTakashiMikiDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHironobuTodaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKentaroEjiriDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasatokiYoshidaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineYusukeNanbaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasashiYoshidaDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineKazufumiNakamuraDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHiroshiMoritaDepartment of Cardiovascular Therapeutics, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHiroshiItoDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineBackground</br>
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.</br>
Methods</br>
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.</br>
Results</br>
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 2 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).</br>
Conclusions</br>
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.MDPIActa Medica Okayama2072-66431312021Secular Decreasing Trend in Plasma Eicosapentaenoic and Docosahexaenoic Acids among Patients with Acute Coronary Syndrome from 2011 to 2019: A Single Center Descriptive Study 253ENTomoakiOkadaDepartment of Cardiology, Kagawa Prefectural Central HospitalToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasayukiDoiDepartment of Cardiology, Kagawa Prefectural Central HospitalKosukeSeiyamaDepartment of Cardiology, Kagawa Prefectural Central HospitalWataruTakagiDepartment of Cardiology, Kagawa Prefectural Central HospitalMasahiroSogoDepartment of Cardiology, Kagawa Prefectural Central HospitalKazumasaNosakaDepartment of Cardiology, Kagawa Prefectural Central HospitalMasahikoTakahashiDepartment of Cardiology, Kagawa Prefectural Central HospitalKeisukeOkawaDepartment of Cardiology, Kagawa Prefectural Central HospitalHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDespite intensive lipid-lowering interventions, patients treated with statins develop atherosclerotic cardiovascular disease (ASCVD), and these patients have an increased risk of developing recurrent cardiovascular events during follow-up. Therefore, there is a need to focus on the residual risks in patients in statin therapy to further reduce ASCVD. The aim of this study was to retrospectively investigate the 10-year trend (2011-2019) regarding changes in polyunsaturated fatty acids (PUFAs) in patients with acute coronary syndrome (ACS) in a single center. We included 686 men and 203 women with ACS admitted to Kagawa Prefectural Central Hospital. Plasma PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-gamma-linolenic acid (DGLA), were measured at admission for suspected ACS. A secular decreasing trend in the levels of EPA and DHA and the EPA/AA ratio, but not of AA and DGLA, was observed. The analyses based on age (>70 or <70 years) and sex showed that the decreasing trend in the levels of EPA and DHA did not depend on age and remained significant only in men. Further studies are needed to obtain robust evidence to justify that the administration of n-3 PUFA contributes to the secondary prevention of ACS.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2072-66431322021High Plasma Docosahexaenoic Acid Associated to Better Prognoses of Patients with Acute Decompensated Heart Failure with Preserved Ejection Fraction371ENNaoakiMatsuoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsushiTakaishiDepartment of Cardiovascular Medicine, Mitoyo General HospitalTakaoKishinoueDepartment of Cardiovascular Medicine, Mitoyo General HospitalKentaroYasuharaDepartment of Cardiovascular Medicine, Mitoyo General HospitalMasafumiTanimotoDepartment of Cardiovascular Medicine, Mitoyo General HospitalYukariNakanoNakano Cardiovascular ClinicNobuhikoOnishiDepartment of Cardiovascular Medicine, Mitoyo General HospitalMasayukiUeedaUeeda Cardiovascular ClinicHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe clinical relevance of polyunsaturated fatty acids (PUFAs) in heart failure remains unclear. The aim of this study was to investigate the association between PUFA levels and the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). This retrospective study included 140 hospitalized patients with acute decompensated HFpEF (median age 84.0 years, 42.9% men). The patients' nutritional status was assessed, using the geriatric nutritional risk index (GNRI), and their plasma levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-gamma-linolenic acid (DGLA) were measured before discharge. The primary outcome was all-cause mortality. During a median follow-up of 23.3 months, the primary outcome occurred in 37 patients (26.4%). A Kaplan-Meier analysis showed that lower DHA and DGLA levels, but not EPA or AA levels, were significantly associated with an increase in all-cause death (log-rank; p < 0.001 and p = 0.040, respectively). A multivariate Cox regression analysis also revealed that DHA levels were significantly associated with the incidence of all-cause death (HR: 0.16, 95% CI: 0.06-0.44, p = 0.001), independent of the GNRI. Our results suggest that low plasma DHA levels may be a useful predictor of all-cause mortality and potential therapeutic target in patients with acute decompensated HFpEF.No potential conflict of interest relevant to this article was reported.ElsevierActa Medica Okayama091450877812020Inhibitory effects of RAGE-aptamer on development of monocrotaline-induced pulmonary arterial hypertension in rats1216ENKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakiyoSakaguchiDepartment of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaofumiAmiokaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesLuh Oliva SaraswatiSuastikaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYuichiroHigashimotoDepartment of Chemistry, Kurume University School of MedicineKeiFukamiDivision of Nephrology, Department of Medicine, Kurume University School of MedicineHiromiMatsubaraDepartment of Cardiology, National Hospital Organization Okayama Medical CenterHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: 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.<br><br>
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.ElsevierActa Medica Okayama0914-50877812021Efficacy of shear wave elastography for evaluating right ventricular myocardial fibrosis in monocrotaline-induced pulmonary hypertension rats1723ENRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKaoruKobayashiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoOhnoKawasaki University of Medical WelfareNaofumiAmiokaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiIto Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Right ventricular (RV) function is important for outcomes in pulmonary hypertension. Evaluation of RV myocardial characteristics is useful to assess the disease severity. Shear wave elastography (SWE) provides information of shear wave (SW) elasticity, which is related to tissue hardness, and SW dispersion slope, which reflects tissue viscosity. This study aimed to test the hypothesis that SW elasticity is increased and SW dispersion slope is decreased in the right ventricle of monocrotaline (MCT)-induced pulmonary hypertension rats. <br>
<br>
Methods: Rats were divided into MCT-induced pulmonary hypertension group (n = 10) and control group (n = 10). SW elasticity and SW dispersion slope were measured on excised hearts. Myocardial fibrosis was evaluated histologically. <br>
<br>
Results: RV hypertrophy was observed in the MCT group. SW elasticity of right ventricle was higher in the MCT group than in the control group (3.5 } 0.9 kPa vs. 2.5 } 0.4 kPa, p < 0.01). SW dispersion slope of right ventricle was lower in the MCT group than in the control group (5.3 } 1.7 m/s/kHz vs. 7.7 } 1.5 m/s/kHz, p < 0.01). The fibrosis area of right ventricle was increased in MCT group compared with control group (18 } 5% vs. 8 } 3%, p < 0.01), and was positively related to SW elasticity and negatively related to SW dispersion slope. <br>
<br>
Conclusions: Higher SW elasticity and lower SW dispersion slope were observed in the fibrotic myocardium of right ventricle in MCT-induced pulmonary hypertension rats. SWE may have the potential to evaluate RV function by assessing myocardial characteristics. No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2077-03831072021Increased Circulating Malondialdehyde-Modified Low-Density Lipoprotein Level Is Associated with High-Risk Plaque in Coronary Computed Tomography Angiography in Patients Receiving Statin Therapy1480ENKeishiIchikawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOsawaDepartment of Cardiovascular Medicine, Japanese Red Cross Okayama HospitalTakashiMikiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesObjective: To evaluate the association of serum malondialdehyde low-density lipoprotein (MDA-LDL), an oxidatively modified LDL, with the prevalence of high-risk plaques (HRP) determined with coronary computed tomography angiography (CTA) in statin-treated patients. Methods: This study was a single-center retrospective cohort comprising 268 patients (mean age 67 years, 58% men) with statin therapy and who underwent coronary CTA for suspected stable coronary artery disease. Patients were classified into two groups according to median MDA-LDL level or median LDL-C level. Coronary CTA-verified HRP was defined when two or more characteristics, including positive remodeling, low-density plaques, and spotty calcification, were present. Results: Patients with HRP had higher MDA-LDL (p = 0.011), but not LDL-C (p = 0.867) than those without HRP. High MDA-LDL was independently associated with HRP (odds ratio 1.883, 95% confidential interval 1.082-3.279) after adjustment for traditional risk factors. Regarding incremental value of MDA-LDL for predicting CTA-verified HRP, addition of serum MDA-LDL levels to the baseline model significantly increased global chi-square score from 26.1 to 32.8 (p = 0.010). Conclusions: A high serum MDA-LDL level is an independent predictor of CTA-verified HRP, which can lead to cardiovascular events in statin-treated patients.No potential conflict of interest relevant to this article was reported.Public Library ScienceActa Medica Okayama1932-62031642021Lack of collagen alpha 6(IV) chain in mice does not cause severe-to-profound hearing loss or cochlear malformation, a distinct phenotype from nonsyndromic hearing loss with COL4A6 missense mutatione0249909ENShaoyingTangDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomokoYonezawaDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukihideMaedaDepartment of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMitsuakiOnoDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroMaebaDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRyusukeMomotaDepartment of Human Morphology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYasukoTomonoDivision of Molecular and Cell Biology, Shigei Medical Research InstituteToshitakaOohashiDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesCongenital hearing loss affects 1 in every 1000 births, with genetic mutations contributing to more than 50% of all cases. X-linked nonsyndromic hereditary hearing loss is associated with six loci (DFNX1-6) and five genes. Recently, the missense mutation (c.1771G>A, p.Gly591Ser) in COL4A6, encoding the basement membrane (BM) collagen alpha 6(IV) chain, was shown to be associated with X-linked congenital nonsyndromic hearing loss with cochlear malformation. However, the mechanism by which the COL4A6 mutation impacts hereditary hearing loss has not yet been elucidated. Herein, we investigated Col4a6 knockout (KO) effects on hearing function and cochlear formation in mice. Immunohistochemistry showed that the collagen alpha 6(IV) chain was distributed throughout the mouse cochlea within subepithelial BMs underlying the interdental cells, inner sulcus cells, basilar membrane, outer sulcus cells, root cells, Reissner's membrane, and perivascular BMs in the spiral limbus, spiral ligament, and stria vascularis. However, the click-evoked auditory brainstem response analysis did not show significant changes in the hearing threshold of Col4a6 KO mice compared with wild-type (WT) mice with the same genetic background. In addition, the cochlear structures of Col4a6 KO mice did not exhibit morphological alterations, according to the results of high-resolution micro-computed tomography and histology. Hence, loss of Col4a6 gene expression in mice showed normal click ABR thresholds and normal cochlear formation, which differs from humans with the COL4A6 missense mutation c.1771G>A, p.Gly591Ser. Therefore, the deleterious effects in the auditory system caused by the missense mutation in COL4A6 are likely due to the dominant-negative effects of the alpha 6(IV) chain and/or alpha 5 alpha 6 alpha 5(IV) heterotrimer with an aberrant structure that would not occur in cases with loss of gene expression.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2047-998010162021Predictive Value of the Cardio-Ankle Vascular Index for Cardiovascular Events in Patients at Cardiovascular Riske020103ENToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKohjiShiraiDepartment of Internal Medicine, Mihama HospitalShigeoHorinakaDepartment of Cardiovascular Medicine, Dokkyo Medical UniversityJitsuoHigakiDepartment of Cardiology, South Matsuyama HospitalShigeoYamamuraFaculty of Pharmaceutical Sciences, Josai International UniversityAtsuhitoSaikiCenter of Diabetes, Endocrine and Metabolism, Toho University Sakura Medical Center, Sakura-CityMaoTakahashiDivision of Cardiovascular Medicine (Sakura), Department of Internal Medicine, Faculty of Medicine, Toho UniversityMitsuruMasakiDivision of Clinical Laboratory Medicine, Department of Cardiovascular and Renal Medicine, Hyogo College of MedicineTakafumiOkuraDepartment of Cardiology, Yawatahama City General HospitalKazuhikoKotaniDivision of Community and Family Medicine, Jichi Medical UniversityTakuroKubozonoDepartment of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima UniversityRyoYoshiokaDepartment of Cardiovascular Medicine, The Sakakibara Heart Institute of OkayamaHajimeKiharaDepartment of Internal Medicine, Kihara Cardiovascular ClinicKojiHasegawaDivision of Translational ResearchNorikoSatoh-AsaharaDepartment of Endocrinology, Metabolism, and Hypertension ResearchHajimeOrimoClinical Research Institute, National Hospital Organization Kyoto Medical CenterBACKGROUND: Arterial stiffness is an important predictor of cardiovascular events; however, indexes for measuring arterial stiffness have not been widely incorporated into routine clinical practice. This study aimed to determine whether the cardio-ankle vascular index (CAVI), based on the blood pressure-independent stiffness parameter beta and reflecting arterial stiffness from the origin of the ascending aorta, is a good predictor of cardiovascular events in patients with cardiovascular disease risk factors in a large prospective cohort. <br>
<br>
METHODS AND RESULTS: This multicenter prospective cohort study, commencing in May 2013, with a 5-year follow-up period, included patients (aged 40-74 years) with cardiovascular disease risks. The primary outcome was the composite of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. Among 2932 included patients, 2001 (68.3%) were men; the mean (SD) age at diagnosis was 63 (8) years. During the median follow-up of 4.9 years, 82 participants experienced primary outcomes. The CAVI predicted the primary outcome (hazard ratio, 1.38; 95% CI, 1.16-1.65; P<0.001). In terms of event subtypes, the CAVI was associated with cardiovascular death and stroke but not with myocardial infarction. When the CAVI was incorporated into a model with known cardiovascular disease risks for predicting cardiovascular events, the global chi(2) value increased from 33.8 to 45.2 (P<0.001), and the net reclassification index was 0.254 (P=0.024). <br>
<br>
CONCLUSIONS: This large cohort study demonstrated that the CAVI predicted cardiovascular events.No potential conflict of interest relevant to this article was reported.Lippincott Williams & WilkinsActa Medica Okayama0025-7974100342021Association between higher pericoronary adipose tissue attenuation measured by coronary computed tomography angiography and nonalcoholic fatty liver disease A matched case-control studye27043ENKeishiIchikawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOsawaDepartment of General Internal Medicine 3, Kawasaki Medical School General Medical CenterTakashiMikiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeMorimitsuDepartment of Medical technology, Okayama University HospitalNoriakiAkagiDepartment of Medical technology, Okayama University HospitalMitsutakaNakashimaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNon-alcoholic fatty liver disease (NAFLD) is a risk factor for cardiac mortality. Pericoronary adipose tissue (PCAT) attenuation, expressed by the fat attenuation index on coronary computed tomography angiography, reflects pericoronary inflammation. We aimed to investigate the association between PCAT attenuation and NAFLD. This is a single-center cohort study comprising of patients who underwent coronary computed tomography angiography for suspected stable coronary artery disease between January and December 2020. Patient characteristics and coronary computed tomography angiography findings were analyzed between patients with NAFLD (n = 78) and a propensity score-matched cohort of patients without NAFLD (n = 78). PCAT attenuation was assessed in Hounsfield units (HU) of proximal 40-mm segments of the left anterior descending artery (LAD) and right coronary artery. The mean PCAT attenuation in LAD and right coronary artery were significantly higher in patients with NAFLD than those without NAFLD. When patients were divided into 2 groups using the median LAD-PCAT attenuation of -72.5 HU, the high PCAT attenuation group had more males (82% vs 67%, P = .028) and NAFLD patients (63% vs 37%, P = .001) compared to the low PCAT attenuation group. No differences in age, body mass index, conventional cardiovascular risk factors, or the presence of high-risk plaque were observed between the 2 groups. In the multivariate logistic analysis, NAFLD was independently associated with high PCAT attenuation (odds ratio 2.912, 95% confidence interval 1.386 to 6.118, P = .005). NAFLD is associated with high PCAT attenuation on coronary computed tomography angiography. This finding suggests that pericoronary inflammation is involved in the increased cardiac mortality in NAFLD patients.No potential conflict of interest relevant to this article was reported.Wiley Periodicals, IncActa Medica Okayama2055-58222021Effects of luseogliflozin on estimated plasma volume in patients with heart failure with preserved ejection fractionENMitsutakaNakashimaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHajimeKiharaDepartment of Internal Medicine, Kihara Cardiovascular ClinicYoshikiHataDepartment of Cardiology, Minamino Cardiovascular HospitalToshihikoNaganoDepartment of Internal Medicine, Iwasa Hospital,AtsushiTakaishiDepartment of Cardiology, Mitoyo General HospitalHironobuTodaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeijiNanbaDepartment of Cardiology, Okayama Rosai HospitalYoichiNakamuraDepartment of Cardiovascular Medicine, Specified Clinic of Soyokaze CardioVascular Medicine and Diabetes Care, MatsuyamaSatoshiAkagiDepartment of Internal Medicine, Akaiwa Medical Association HospitalSatoruSakuragiDepartment of Cardiovascular Medicine, Iwakuni Clinical CenterTaroMinagawaDepartment of Internal Medicine, Minagawa Cardiovascular ClinicYusukeKawaiDepartment of Cardiovascular Medicine, Okayama City HospitalNobuhiroNishiiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSoichiroFukeDepartment of Cardiovascular Medicine, Japanese Red Cross Okayama HospitalMasakiYoshikawaDepartment of Cardiology, Fukuyama City HospitalKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMUSCAT-HF Study InvestigatorsAims<br>
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). <br>
Methods and results<br>
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). <br>
Conclusions<br>
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.Nature PortfolioActa Medica Okayama2045-23221112021Efficacy of shear wave elasticity for evaluating myocardial hypertrophy in hypertensive rats22812ENYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroakiOhtsukaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNaofumiAmiokaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKaoruAkazawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoOhnoKawasaki University of Medical WelfareKeishiIchikawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukihiroSaitoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesShear wave (SW) imaging is a novel ultrasound-based technique for assessing tissue characteristics. SW elasticity may be useful to assess the severity of hypertensive left ventricular (LV) hypertrophy. This study aimed to evaluate the efficacy of SW elasticity for assessing the degree of myocardial hypertrophy using hypertensive rats. Rats were divided into hypertension group and control group. SW elasticity was measured on the excised heart. Myocardial hypertrophy was assessed histologically. LV weight was greater in hypertension group. An increase in interventricular septum and LV free wall thicknesses was observed in hypertension group. SW elasticity was significantly higher in hypertension group than in control group (14.6 +/- 4.3 kPa vs. 6.5 +/- 1.1 kPa, P < 0.01). The cross-sectional area of cardiomyocytes was larger in hypertension group than in control group (397 +/- 50 mu m(2) vs. 243 +/- 14 mu m(2), P < 0.01), and SW elasticity was positively correlated with the cross-sectional area of cardiomyocytes (R = 0.96, P < 0.01). This study showed that SW elasticity was higher in hypertensive rats and was closely correlated with the degree of myocardial hypertrophy, suggesting the efficacy of SW elasticity for estimating the severity of hypertensive LV hypertrophy.No potential conflict of interest relevant to this article was reported.BMCActa Medica Okayama1475-28402112022High pericoronary adipose tissue attenuation on computed tomography angiography predicts cardiovascular events in patients with type 2 diabetes mellitus: post-hoc analysis from a prospective cohort study44ENKeishiIchikawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOsawaDepartment of General Internal Medicine 3, Kawasaki Medical School General Medicine CentreMitsutakaNakashimaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiMikiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroNishiharaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHironobuTodaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatokiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) is a non-invasive biomarker for pericoronary inflammation. We aimed to investigate the prognostic value of PCAT attenuation in patients with type 2 diabetes mellitus (T2DM). Methods We included 333 T2DM patients (mean age, 66 years; male patients, 211; mean body mass index, 25 kg/m(2)) who underwent clinically indicated coronary CTA and examined their CT findings, coronary artery calcium score, pericardial fat volume, stenosis (> 50% luminal narrowing), high-risk plaque features of low-attenuation plaque and/or positive remodelling and/or spotty calcification, and PCAT attenuation. We assessed PCAT attenuation in Hounsfield units (HU) of proximal 40-mm segments of the left anterior descending artery (LAD) and right coronary artery (RCA). Cardiovascular events were defined as cardiac death, hospitalisation for acute coronary syndrome, late coronary revascularisation, and hospitalisation for heart failure. Results During a median follow-up of 4.0 years, we observed 31 cardiovascular events. LAD-PCAT attenuation was significantly higher in patients with cardiovascular events than in those without (- 68.5 +/- 6.5 HU vs - 70.8 +/- 6.1 HU, p = 0.045), whereas RCA-PCAT attenuation was not (p = 0.089). High LAD-PCAT attenuation (> - 70.7 HU; median value) was significantly associated with cardiovascular events in a model that included adverse CTA findings, such as significant stenosis and/or high-risk plaque (hazard ratio; 2.69, 95% confidence interval; 1.17-0.20, p = 0.020). After adding LAD-PCAT attenuation to the adverse CTA findings, the C-statistic and global chi-square values increased significantly from 0.65 to 0.70 (p = 0.037) and 10.9-15.0 (p = 0.043), respectively. Conclusions In T2DM patients undergoing clinically indicated coronary CTA, high LAD-PCAT attenuation could significantly predict cardiovascular events. This suggests that assessing LAD-PCAT attenuation can help physicians identify high-risk T2DM patients.No potential conflict of interest relevant to this article was reported.Elsevier BVActa Medica Okayama0914-50877932022Fragmented QRS as a predictor of cardiac events in patients with cardiac sarcoidosis446452ENSoichiroOguraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMoritaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiNakagawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhiroNishiiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNorihisaTohDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAtsuyukiWatanabeDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesBackground: Multiple spikes within the QRS complex, known as fragmented QRS (fQRS),
are associated with the occurrences of ventricular arrhythmic events (VAEs) in patients with
Brugada syndrome and hypertrophic cardiomyopathy. However, the association between
fQRS and occurrence of VAEs in patients with cardiac sarcoidosis (CS) has not been
elucidated.<br>
Methods: We evaluated the associations between fQRS and cardiac events including VAEs
(non-sustained ventricular tachycardia [NSVT], sustained ventricular tachycardia [VT], and
ventricular fibrillation [VF]), hospitalization for heart failure, and all cause death in 68
patients with CS (30 patients with fQRS vs. 38 patients without fQRS) over a 5-year period.<br>
Results: Cardiac events occurred in 22 patients with fQRS and 18 patients without fQRS
(73% vs. 47%, P=0.009). Of the cardiac events that occurred in CS patients, VAEs occurred
more frequently in patients with fQRS than in patients without fQRS (VAEs: 70% vs. 45%,
P=0.017; NSVT: 70% vs. 45%, P=0.010; VT: 43% vs. 18%, P=0.011, and VF: 6.7% vs.
2.6%, P=0.34), whereas there was no significant difference in hospitalization for heart failure
or all-cause death between patients with and those without fQRS (hospitalization for heart
failure: 6.7% vs. 5.3%, P=0.75; all-cause death: 6.7% vs. 5.3%, P=0.64). Multivariate analysis
showed that fQRS in the baseline ECG was independently associated with VAEs (hazard ratio
[HR]: 2.21, 95% confidence interval [CI]: 1.15–4.25, P=0.017).<br>
Conclusion: fQRS is a predictor of VAEs in patients with CS.<br>No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-00672372022Pathophysiology and Treatment of Diabetic Cardiomyopathy and Heart Failure in Patients with Diabetes Mellitus3587ENKazufumiNakamuraDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruMiyoshiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasashiYoshidaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoshiAkagiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukihiroSaitoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKentaroEjiriDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaoakiMatsuoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeishiIchikawaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeiichiroIwasakiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakanoriNaitoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYusukeNambaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasatokiYoshidaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHirokiSugiyamaDepartment of Internal Medicine, Okayama Saiseikai General HospitalHiroshiItoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityThere 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.BMCActa Medica Okayama1757-65121312022Enhancement of pacing function by HCN4 overexpression in human pluripotent stem cell-derived cardiomyocytes141ENYukihiroSaitoDepartment of Cardiovascular Medicine, Okayama University HospitalKazufumiNakamuraDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineMasashiYoshidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Dentistry, and Pharmaceutical Science, Okayama University Graduate School of MedicineHirokiSugiyamaDepartment of Internal Medicine, Okayama Saiseikai General HospitalSatoshiAkagiDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineToruMiyoshiDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHiroshiMoritaDepartment of Cardiovascular Therapeutics, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineHiroshiItoDepartment of Cardiovascular Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of MedicineBackground The number of patients with bradyarrhythmia and the number of patients with cardiac pacemakers are increasing with the aging population and the increase in the number of patients with heart diseases. Some patients in whom a cardiac pacemaker has been implanted experience problems such as pacemaker infection and inconvenience due to electromagnetic interference. We have reported that overexpression of HCN channels producing a pacemaker current in mouse embryonic stem cell-derived cardiomyocytes showed enhanced pacing function in vitro and in vivo. The aim of this study was to determine whether HCN4 overexpression in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can strengthen the pacing function of the cells. Methods Human HCN4 was transduced in the AAVS1 locus of human induced pluripotent stem cells by nucleofection and HCN4-overexpressing iPSC-CMs were generated. Gene expression profiles, frequencies of spontaneous contraction and pacing abilities of HCN4-overexpressing and non-overexpressing iPSC-CMs in vitro were compared. Results HCN4-overexpressing iPSC-CMs showed higher spontaneous contraction rates than those of non-overexpressing iPSC-CMs. They responded to an HCN channel blocker and beta adrenergic stimulation. The pacing rates against parent iPSC line-derived cardiomyocytes were also higher in HCN4-overexpressing iPSC-CMs than in non-overexpressing iPSC-CMs. Conclusions Overexpression of HCN4 showed enhancement of I-f current, spontaneous firing and pacing function in iPSC-CMs. These data suggest this transgenic cell line may be useful as a cardiac pacemaker.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221212022LCZ696 ameliorates doxorubicin-induced cardiomyocyte toxicity in rats4930ENToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNaofumiAmiokaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityOmer F.HatipogluDepartment of Pharmacology, Kindai UniversityTomokoYonezawaDepartment of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceYukihiroSaitoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesDoxorubicin (DOX)-based chemotherapy induces cardiotoxicity, which is considered the main bottleneck for its clinical application. In this study, we investigated the potential benefit of LCZ696, an angiotensin receptor-neprilysin inhibitor against DOX-induced cardiotoxicity in rats and H9c2 cells and determined whether the mechanism underlying any such effects involves its antioxidant activity. Male Sprague-Dawley rats were randomly separated into four groups, each consisting of 15 rats (DOX (1.5 mg/kg/day intraperitoneally for 10 days followed by non-treatment for 8 days); DOX + valsartan (31 mg/kg/day by gavage from day 1 to day 18); DOX + LCZ696 (68 mg/kg/day by gavage from day 1 to day 18); and control (saline intraperitoneally for 10 days). DOX-induced elevation of cardiac troponin T levels on day 18 was significantly reduced by LCZ696, but not valsartan. The DOX-induced increase in myocardial reactive oxygen species (ROS) levels determined using dihydroethidium was significantly ameliorated by LCZ696, but not valsartan, and was accompanied by the suppression of DOX-induced increase in p47phox. LCZ696 recovered the DOX-induced decrease in phosphorylation of adenosine monophosphate-activated protein kinase and increased the ratio of Bax and Bcl-2. In H9c2 cardiomyocytes, LCZ696 reduced DOX-induced mitochondrial ROS generation and improved cell viability more than valsartan. Our findings indicated that LCZ696 ameliorated DOX-induced cardiotoxicity in rat hearts in vivo and in vitro, possibly by mediating a decrease in oxidative stress.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221212022Impact of shear wave dispersion slope analysis for assessing the severity of myocarditis8776ENNaofumiAmiokaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMegumiKondoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKaoruAkazawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukoOhnoKawasaki University of Medical WelfareKeishiIchikawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukihiroSaitoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMoritaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThis study aimed to elucidate the utility of a novel ultrasound-based technique, shear wave dispersion slope (SWDS) analysis, which estimates tissue viscosity, for evaluating the severity of myocardial inflammation. Experimental autoimmune myocarditis (EAM) at different disease phases [3-week (acute phase): n = 10, 5-week (subacute phase): n = 9, and 7-week (late phase): n = 11] were developed in male Lewis rats. SWDS was measured in the right and the left ventricular free walls (RVFW and LVFW) under a retrograde perfusion condition. Histological myocardial inflammation was evaluated by CD68 staining. The accumulation of CD68-positive cells was severe in the myocardium of the EAM 3-week group. The median (interquartile range) SWDS of RVFW was significantly higher in the EAM 3-week group [9.9 (6.5-11.0) m/s/kHz] than in the control group [5.4 (4.5-6.8) m/s/kHz] (P = 0.034). The median SWDS of LVFW was also significantly higher in the EAM 3-week group [8.1 (6.4-11.0) m/s/kHz] than in the control group [4.4 (4.2-4.8) m/s/kHz] (P = 0.003). SWDS and the percentage of CD68-positive area showed a significant correlation in RVFW (R-2 = 0.64, P < 0.001) and LVFW (R-2 = 0.73, P < 0.001). This study showed that SWDS was elevated in ventricular walls with acute inflammation and also significantly correlated with the degree of myocardial inflammation. These results suggest the potential of SWDS in estimating the histological severity of acute myocarditis.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2308-3425952022Effect of Early Initiation of Evolocumab on Lipoprotein(a) in Patients with Acute Myocardial Infarction: Sub-Analysis of a Randomized Controlled Trial153ENTomoakiOkadaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruMiyoshiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayukiDoiDepartment of Cardiology, Kagawa Prefectural Central HospitalKazumasaNosakaDepartment of Cardiology, Kagawa Prefectural Central HospitalRyuTsushimaDepartment of Cardiology, Kagawa Prefectural Central HospitalSatokoUgawaDepartment of Cardiology, Kagawa Prefectural Central HospitalWataruTakagiDepartment of Cardiology, Kagawa Prefectural Central HospitalMasahiroSogoDepartment of Cardiology, Kagawa Prefectural Central HospitalMasahikoTakahashiDepartment of Cardiology, Kagawa Prefectural Central HospitalHiroshiItoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityElevated circulating lipoprotein(a) levels are associated with an increased risk of cardiovascular events. We reported that early initiation of evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in addition to a statin substantially reduced the lipoprotein(a) levels in patients with acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PCI). This sub-analysis sought to investigate the effect of evolocumab on lipoprotein(a) based on baseline lipoprotein(a) levels and characteristics. This study was a prespecified analysis of a randomized controlled trial that enrolled 102 patients who underwent primary PCI for AMI. Patients received pitavastatin (2 mg/day) alone or pitavastatin and evolocumab 140 mg subcutaneously within 24 h and 2 weeks after the index PCI. The evolocumab group showed significantly suppressed lipoprotein(a) levels in patients with baseline lipoprotein(a) levels of <= 10 mg/dL, 10 < lipoprotein(a) <= 20 mg/dL, and >20 mg/dL compared with the control group, as well as similar reductions in lipoprotein(a) levels in all patient subgroups. Among these subgroups, evolocumab tended to show more favorable effects in patients with diabetes mellitus. In AMI patients, early initiation of evolocumab therapy within 24 h of primary PCI suppressed the increase in lipoprotein(a) levels within 4 weeks, regardless of baseline levels and characteristics.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2077-038311102022Association of Oxidized Low-Density Lipoprotein in Nonalcoholic Fatty Liver Disease with High-Risk Plaque on Coronary Computed Tomography Angiography: A Matched Case-Control Study2838ENTakahiroNishiharaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruMiyoshiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeishiIchikawaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazuhiroOsawaDepartment of General Internal Medicine 3, Kawasaki Medical School General Medicine CentreMitsutakaNakashimaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiMikiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiItoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNonalcoholic fatty liver disease (NAFLD) is a risk factor for the development of atherosclerotic cardiovascular diseases (CVDs), and oxidative stress has been proposed as a shared pathophysiological condition. This study examined whether oxidized low-density lipoprotein (LDL) is involved in the underlying mechanism that links coronary atherosclerosis and NAFLD. This study included 631 patients who underwent coronary computed tomography angiography (CTA) for suspected coronary artery disease. NAFLD was defined on CT images as a liver-to-spleen attenuation ratio of <1.0. Serum-malondialdehyde-modified LDL (MDA-LDL) and coronary CTA findings were analyzed in a propensity-score-matched cohort of patients with NAFLD (n = 150) and those without NAFLD (n = 150). This study analyzed 300 patients (median age, 65 years; 64% men). Patients with NAFLD had higher MDA-LDL levels and a greater presence of CTA-verified high-risk plaques than those without NAFLD. In the multivariate linear regression analysis, MDA-LDL was independently associated with NAFLD (beta = 11.337, p = 0.005) and high-risk plaques (beta = 12.487, p = 0.007). Increased MDA-LDL may be a mediator between NAFLD and high-risk coronary plaque on coronary CTA. Increased oxidative stress in NAFLD, as assessed using MDA-LDL, may be involved in the development of CVDs.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2050-09041072022Lotus root-like appearance in the left anterior descending artery treated with a drug-coated balloon angioplastye06028ENWataruTakagiDepartment of Cardiology, Kagawa Prefectural Central HospitalTomoakiOkadaDepartment of Cardiology, Kagawa Prefectural Central HospitalKazumasaNosakaDepartment of Cardiology, Kagawa Prefectural Central HospitalToruMiyoshiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasayukiDoiDepartment of Cardiology, Kagawa Prefectural Central HospitalA lotus root-like appearance of the coronary artery diagnosed by optical coherence tomography (OCT) is characterized by old coronary thrombi that form small lumen channels. Herein, serial OCT images of a left anterior descending artery with a lotus root-like appearance, treated with drug-coated balloon angioplasty are described.No potential conflict of interest relevant to this article was reported.Frontiers Media SAActa Medica Okayama2297-055X92022Pemafibrate Prevents Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms904215ENNaofumiAmiokaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruMiyoshiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTomokoYonezawaDepartment of Molecular Biology and Biochemistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMegumiKondoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoshiAkagiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasashiYoshidaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukihiroSaitoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazufumiNakamuraDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiItoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: Abdominal aortic aneurysm (AAA) is a life-threatening disease that lacks effective preventive therapies. This study aimed to evaluate the effect of pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPAR alpha) agonist, on AAA formation and rupture. <br>
Methods: Experimental AAA was induced by subcutaneous angiotensin II (AngII) infusion in ApoE(-)(/)(-) mice for 4 weeks. Pemafibrate (0.1 mg/kg/day) was administered orally. Dihydroethidium staining was used to evaluate the reactive oxygen species (ROS). <br>
Results: The size of the AngII-induced AAA did not differ between pemafibrate- and vehicle-treated groups. However, a decreased mortality rate due to AAA rupture was observed in pemafibrate-treated mice. Pemafibrate ameliorated AngII-induced ROS and reduced the mRNA expression of interleukin-6 and tumor necrosis factor-alpha in the aortic wall. Gelatin zymography analysis demonstrated significant inhibition of matrix metalloproteinase-2 activity by pemafibrate. AngII-induced ROS production in human vascular smooth muscle cells was inhibited by pre-treatment with pemafibrate and was accompanied by an increase in catalase activity. Small interfering RNA-mediated knockdown of catalase or PPAR alpha significantly attenuated the anti-oxidative effect of pemafibrate. <br>
Conclusion: Pemafibrate prevented AAA rupture in a murine model, concomitant with reduced ROS, inflammation, and extracellular matrix degradation in the aortic wall. The protective effect against AAA rupture was partly mediated by the anti-oxidative effect of catalase induced by pemafibrate in the smooth muscle cells.No potential conflict of interest relevant to this article was reported.Wiley Periodicals, IncActa Medica Okayama2055-58222022High platelet reactivity is a predictor of left ventricular remodelling in patients with acute myocardial infarctionENMasahiroTsujiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYusukeKawaiDepartment of Cardiovascular Medicine, Okayama City HospitalToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesEisukeSaitoDepartment of Cardiovascular Medicine, Okayama City HospitalKoheiKawamuraDepartment of Cardiovascular Medicine, Okayama City HospitalTamakiOnoDepartment of Cardiovascular Medicine, Okayama City HospitalKojiTokiokaDepartment of Cardiovascular Medicine, Okayama City HospitalTohruOheDepartment of Cardiovascular Medicine, Okayama City HospitalKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences HiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Aims Acute myocardial infarction (AMI) is associated with left ventricular remodelling (LVR), which leads to progressive heart failure. Platelets play a pivotal role in promoting systemic and cardiac inflammatory responses during the complex process of myocardial wound healing or repair following AMI. This study aimed to investigate the impact of platelet reactivity immediately after primary percutaneous coronary intervention (PCI) on LVR in AMI patients with ST-segment (STEMI) and nonST-segment elevation (NSTEMI). <br>
Methods and results This prospective, single-centre, observational study included 182 patients with AMI who underwent primary PCI (107 patient with STEMI and 75 patients with NSTEMI). Patients were administered a loading dose of aspirin plus prasugrel before the procedure, and platelet reactivity was assessed using the VerifyNow P2Y12 assay immediately after PCI. Echocardiography was performed before discharge and during the chronic phase (8 +/- 3 months after discharge). LVR was defined as a relative >= 20% increase in left ventricular end-diastolic volume index (LVEDVI). LVR in chronic phase was found in 34 patients (18.7%) whose platelet reactivity was significantly higher than those without LVR (259.6 +/- 61.5 and 213.1 +/- 74.8 P2Y12 reaction units [PRU]; P = 0.001). The occurrence of LVR did not differ between patients with STEMI and patients with NSTEMI (21.5% and 14.7%; P = 0.33). The optimal cut-off value of platelet reactivity for discriminating LVR was >= 245 PRU. LVEDVI significantly decreased at chronic phase in patients without high platelet reactivity (<245 PRU) (from 49.2 +/- 13.5 to 45.4 +/- 15.8 ml/m(2); P = 0.02), but not in patients with high platelet reactivity (>= d245 PRU) (P = 0.06). Multivariate logistic analysis showed that high platelet reactivity was an independent predictor of LVR after adjusting for LVEDVI before discharge (odds ratio, 4.13; 95% confidence interval, 1.85-9.79). <br>
Conclusions High platelet reactivity measured immediately after PCI was a predictor of LVR in patients with AMI during the chronic phase. The role of antiplatelet therapy on inflammation in the myocardium is a promising area for further research.No potential conflict of interest relevant to this article was reported.Japanese Circulation SocietyActa Medica Okayama1346-98438682022Overview of the 86th Annual Scientific Meeting of the Japanese Circulation Society@\ Cardiology Spreading Its Wings \13121318ENKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNorihisaTohDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYukihiroSaitoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatokiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiNakagawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKawadaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHironobuTodaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiMikiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesFumiYokohamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeishiIchikawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMakikoTaniyamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesNobuhiroNishiiDepartment of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTeijiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMoritaDepartment of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe 86th Annual Scientific Meeting of the Japanese Circulation Society was held in a web-based format on March 11-13, 2022. In accordance with the internationalization policy of the JCS, the meeting was held with the Asian Pacific Society of Cardiology Congress 2022. The main theme was "Cardiology Spreading its Wings". The number of patients with heart failure and other cardiovascular diseases is increasing dramatically, and the fields dealt with by cardiovascular medicine are also greatly expanding. This conference was both intellectually satisfying and exciting for all participants, who numbered over 14,900. The meeting was completed with great success, and the enormous amount of cooperation and support from all involved was greatly appreciated.No potential conflict of interest relevant to this article was reported.Nature PortfolioActa Medica Okayama2045-23221212022Effects of luseogliflozin and voglibose on high-risk lipid profiles and inflammatory markers in diabetes patients with heart failure15449ENKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHajimeKiharaDepartment of Internal Medicine, Kihara Cardiovascular ClinicYoshikiHataDepartment of Cardiology, Minamino Cardiovascular HospitalToshihikoNaganoDepartment of Internal Medicine, Iwasa HospitalAtsushiTakaishiDepartment of Cardiology, Mitoyo General HospitalHironobuTodaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeijiNambaDepartment of Cardiology, Okayama Rosai HospitalYoichiNakamuraDepartment of Cardiovascular Medicine, Specifed Clinic of Soyokaze Cardiovascular Medicine and Diabetes CareSatoshiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoruSakuragiDepartment of Cardiovascular Medicine, Iwakuni Clinical CenterTaroMinagawaDepartment of Internal Medicine, Minagawa Cardiovascular ClinicYusukeKawaiDepartment of Cardiovascular Medicine, Okayama City HospitalNobuhiroNishiiDepartment of Internal Medicine, Yoshinaga HospitalSoichiroFukeDepartment of Cardiovascular Medicine, Japanese Red Cross Okayama HospitalMasakiYoshikawaDepartment of Cardiology, Fukuyama City HospitalKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe MUSCAT-HF Study InvestigatorsSodium-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.MDPIActa Medica Okayama2308-34259102022The Association of Triglyceride to High-Density Lipoprotein Cholesterol Ratio with High-Risk Coronary Plaque Characteristics Determined by CT Angiography and Its Risk of Coronary Heart Disease329ENYujiKoideDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakahiroNishiharaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMitsutakaNakashimaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeishiIchikawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTakashiMikiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOsawaDepartment of General Internal Medicine 3, Kawasaki Medical School General Medicine CenterHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesThe triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is an independent risk index for cardiovascular events. This study aimed to evaluate the association between TG/HDL-C ratio and coronary plaque characteristics as seen on coronary computed tomography angiography (CCTA) and the corresponding increase in the likelihood of cardiovascular events. A total of 935 patients who underwent CCTA for suspected coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined based on three characteristics: positive remodeling, low-density plaques, and spotty calcification. Significant stenosis was defined as luminal narrowing of >70%. Patients with a higher TG/HDL-C ratio showed significantly greater prevalence of HRP and significant stenosis than patients with low TG/HDL-C ratios (p < 0.01). Multivariate logistic analysis demonstrated that the TG/HDL-C ratio was significantly associated with the presence of HRP (p < 0.01) but not with significant coronary stenosis (p = 0.24). During the median follow-up period of 4.1 years, 26 cardiovascular events including cardiovascular death and acute coronary syndrome occurred. The highest TG/HDL-C tertile was associated with cardiovascular events, with the lowest TG/HDL-C tertile as the reference (hazard ratio, 3.75; 95% confidence interval, 1.04-13.50). A high TG/HDL-C ratio is associated with the presence of CCTA-verified HRP, which can lead to cardiovascular events in patients with suspected CAD.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2308-34259112022Cardio-Ankle Vascular Index as an Arterial Stiffness Marker Improves the Prediction of Cardiovascular Events in Patients without Cardiovascular Diseases368ENYukoOkamotoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeishiIchikawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSeveral studies have reported that the cardio-ankle vascular index (CAVI), a non-invasive measurement of arterial stiffness, is associated with the incidence of cardiovascular events. We investigated whether adding CAVI to a risk score improves the prediction of cardiovascular events in the setting of primary prevention. This retrospective observational study included consecutive 554 outpatients with cardiovascular disease risk factors but without known cardiovascular disease (68 +/- 9 years, 64% men). The CAVI was measured using the VaSera vascular screening system. Major adverse cardiovascular events (MACE) included cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization. During a median follow-up of 4.3 years, cardiovascular events occurred in 65 patients (11.7%). Multivariate Cox analysis showed that abnormal CAVI (>9.0) was significantly associated with the incidence of MACE (hazard ratio 2.31, 95% confidence interval 1.27-4.18). The addition of CAVI to the Suita score, a conventional risk score for coronary heart disease in Japan, significantly improved the C statics from 0.642 to 0.713 (p = 0.04). In addition to a conventional risk score, CAVI improved the prediction of cardiovascular events in patients with cardiovascular disease risk factors but without known cardiovascular diseases.No potential conflict of interest relevant to this article was reported.WILEYActa Medica Okayama2050-09041022022Fulminant myocarditis after the second dose of COVID-19 mRNA vaccinatione05378ENAkihiroOkaDepartment of Cardiology, Kagawa Prefectural Central HospitalYuyaSudoDepartment of Cardiology, Kagawa Prefectural Central HospitalToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasatomoOzakiDepartment of Cardiology, Kagawa Prefectural Central HospitalYutaKimuraDepartment of Cardiology, Kagawa Prefectural Central HospitalWataruTakagiDepartment of Cardiology, Kagawa Prefectural Central HospitalSatokoUgawaDepartment of Cardiology, Kagawa Prefectural Central HospitalTomoakiOkadaDepartment of Cardiology, Kagawa Prefectural Central HospitalKazumasaNosakaDepartment of Cardiology, Kagawa Prefectural Central HospitalMasayukiDoiDepartment of Cardiology, Kagawa Prefectural Central HospitalMyocarditis is an adverse event associated with coronavirus disease 2019 (COVID-19) mRNA vaccination. A 50-year-old man presented with dyspnea and resting chest pain after receiving the second dose of the COVID-19 mRNA vaccine and developed cardiogenic shock. Fulminant myocarditis was diagnosed by endomyocardial biopsy and treated with intravenous corticosteroids.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-00672432023Microcalcification and Tc-99m-Pyrophosphate Uptake without Increased Bone Metabolism in Cardiac Tissue from Patients with Transthyretin Cardiac Amyloidosis1921ENAtsushiMoriDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukihiroSaitoDepartment of Cardiovascular Medicine, Okayama University HospitalKazufumiNakamuraDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshihiroIidaDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoshiAkagiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasashiYoshidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMakikoTaniyamaDepartment of General Medicine, Tamano Division, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruMiyoshiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiItoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTransthyretin cardiac amyloidosis (ATTR-CA) is characterized by high Tc-99m-labeled bone tracer uptake in the heart. However, the mechanism of bone tracer uptake into the heart remains controversial. Since bone tracer uptake into metastatic bone tumors is thought to be associated with increased bone metabolism, we examined Tc-99m-pyrophosphate (PYP) scintigraphy findings, endomyocardial biopsy (EMB) tissue findings, and the expression of bone metabolism-related genes in the EMB tissues in patients with ATTR-CA, amyloid light-chain cardiac amyloidosis (AL-CA), and noncardiac amyloidosis (non-CA) in this study. The uptake of Tc-99m-PYP in the heart was significantly higher in the ATTR-CA patients than in the AL-CA and non-CA patients. A higher percentage of ATTR-CA EMB tissue showed von Kossa-positive microparticles: ATTR-CA, 62%; AL-CA, 33%; and non-CA, 0%. Calcified microparticles were identified using transmission electron microscopy. However, none of the osteogenic marker genes, osteoclastic marker genes, or phosphate/pyrophosphate-related genes were upregulated in the EMB samples from ATTR-CA patients compared to those from AL-CA and non-CA patients. These results suggest that active calcification-promoting mechanisms are not involved in the microcalcification observed in the heart in ATTR-CA. The mechanisms explaining bone tracer uptake in the heart, which is stronger than that in the ribs, require further investigation.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2072-66431532023Association between Cardiovascular Disease and Liver Disease, from a Clinically Pragmatic Perspective as a Cardiologist748ENMitsutakaNakashimaDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazufumiNakamuraDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakahiroNishiharaDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKeishiIchikawaDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityRieNakayamaDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYoichiTakayaDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityNorihisaTohDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoshiAkagiDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruMiyoshiDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTeijiAkagiDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiItoDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityCardiovascular diseases and liver diseases are closely related. Non-alcoholic fatty liver disease has the same risk factors as those for atherosclerotic cardiovascular disease and may also be a risk factor for atherosclerotic cardiovascular disease on its own. Heart failure causes liver fibrosis, and liver fibrosis results in worsened cardiac preload and congestion. Although some previous reports regard the association between cardiovascular diseases and liver disease, the management strategy for liver disease in patients with cardiovascular diseases is not still established. This review summarized the association between cardiovascular diseases and liver disease. In patients with non-alcoholic fatty liver disease, the degree of liver fibrosis progresses with worsening cardiovascular prognosis. In patients with heart failure, liver fibrosis could be a prognostic marker. Liver stiffness assessed with shear wave elastography, the fibrosis-4 index, and non-alcoholic fatty liver disease fibrosis score is associated with both liver fibrosis in patients with liver diseases and worse prognosis in patients with heart failure. With the current population ageing, the importance of management for cardiovascular diseases and liver disease has been increasing. However, whether management and interventions for liver disease improve the prognosis of cardiovascular diseases has not been fully understood. Future investigations are needed.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama1422-00672432023Are Non-Invasive Modalities for the Assessment of Atherosclerosis Useful for Heart Failure Predictions?1925ENKazuhiroOsawaDepartment of General Internal Medicine 3, Kawasaki Medical School General Medical CenterToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHeart failure (HF) is becoming an increasingly common issue worldwide and is associated with significant morbidity and mortality, making its prevention an important clinical goal. The criteria evaluated using non-invasive modalities such as coronary artery calcification, the ankle-brachial index, and carotid intima-media thickness have been proven to be effective in determining the relative risk of atherosclerotic cardiovascular disease. Notably, risk assessments using these modalities have been proven to be superior to the traditional risk predictors of cardiovascular disease. However, the ability to assess HF risk has not yet been well-established. In this review, we describe the clinical significance of such non-invasive modalities of atherosclerosis assessments and examine their ability to assess HF risk. The predictive value could be influenced by the left ventricular ejection fraction. Specifically, when the ejection fraction is reduced, its predictive value increases because this condition is potentially a result of coronary artery disease. In contrast, using these measures to predict HF with a preserved ejection fraction may be difficult because it is a heterogeneous condition. To overcome this issue, further research, especially on HF with a preserved ejection fraction, is required.No potential conflict of interest relevant to this article was reported.Japan Atherosclerosis SocietyActa Medica Okayama1340-34783042023Association between High Pericoronary Adipose Tissue Computed Tomography Attenuation and Impaired Flow-Mediated Dilation of the Brachial Artery364376ENKeishiIchikawaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruMiyoshiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukoOhnoDepartment of Medical technology, Kawasaki University of Medical WelfareKazuhiroOsawaDepartment of General Internal Medicine 3, Kawasaki Medical School General Medicine CenterMitsutakaNakashimaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakahiroNishiharaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiMikiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHironobuTodaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasatokiYoshidaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiItoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityAims: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTA) is a noninvasive biomarker for pericoronary inflammation and is associated with cardiac mortality. We aimed to investigate the association between PCAT attenuation and endothelial dysfunction assessed using flow-mediated dilation (FMD).<br>
Methods: A total of 119 outpatients who underwent both coronary CTA and FMD measurements were examined. PCAT attenuation values were assessed at the proximal 40-mm segments of all three major coronary arteries on coronary CTA. Endothelial function was assessed using FMD. Patients were then classified into two groups: those with endothelial dysfunction (FMD 4%, n=44) and those without endothelial dysfunction (FMD ≥ 4%, n=75).<br>
Results: In all three coronary arteries, PCAT attenuation was significantly higher in patients with endothelial dysfunction than in those without endothelial dysfunction. Multivariate logistic regression analysis revealed that PCAT attenuation in the right coronary artery (odds ratio [OR]=1.543; 95% confidence interval [CI]=1.004–2.369, p=0.048) and left anterior descending artery (OR=1.525, 95% CI=1.004–2.369, p=0.049) was an independent predictor of endothelial dysfunction. Subgroup analysis of patients with adverse CTA findings (significant stenosis and/or high-risk plaque) and those with coronary artery calcium score 100 showed that high PCAT attenuation in all three coronary arteries was a significant predictor of endothelial dysfunction.<br>
Conclusion: High PCAT attenuation was significantly associated with FMD-assessed endothelial dysfunction in patients with suspected coronary artery disease. Our results suggest that endothelial dysfunction is one of the pathophysiological mechanisms linking pericoronary inflammation to cardiac mortality.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2308-34251052023Diagnostic Performance of Cardiac Computed Tomography for Detecting Patent Foramen Ovale: Evaluation Using Transesophageal Echocardiography and Catheterization as Reference Standards193ENTakashiMikiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKojiNakagawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKeishiIchikawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTomofumiMizunoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesRieNakayamaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatoshiKawadaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasakazuMiyamotoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesTeijiAkagiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiIto Department of General Internal Medicine 3, Kawasaki Medical SchoolBackground: Patent foramen ovale (PFO) is associated with various diseases such as cryptogenic stroke, migraine, and platypnea-orthodeoxia syndrome. This study aimed to evaluate the diagnostic performance of cardiac computed tomography (CT) for PFO detection. Materials and Methods: Consecutive patients diagnosed with atrial fibrillation and who underwent catheter ablation with pre-procedural cardiac CT and transesophageal echocardiography (TEE) were enrolled in this study. The presence of PFO was defined as (1) the confirmation of PFO using TEE and/or (2) the catheter crossing the interatrial septum (IAS) into the left atrium during ablation. CT findings indicative of PFO included (1) the presence of a channel-like appearance (CLA) on the IAS and (2) a CLA with a contrast jet flow from the left atrium to the right atrium. The diagnostic performance of both a CLA alone and a CLA with a jet flow was evaluated for PFO detection. Results: Altogether, 151 patients were analyzed in the study (mean age, 68 years; men, 62%). Twenty-nine patients (19%) had PFO confirmed by TEE and/or catheterization. The diagnostic performance of a CLA alone was as follows: sensitivity, 72.4%; specificity, 79.5%; positive predictive value (PPV), 45.7%; negative predictive value (NPV), 92.4%. The diagnostic performance of a CLA with a jet flow was as follows: sensitivity, 65.5%; specificity, 98.4%; PPV, 90.5%; NPV, 92.3%. The diagnostic performance of a CLA with a jet flow was statistically superior to that of a CLA alone (p = 0.045), and the C-statistics were 0.76 and 0.82, respectively. Conclusion: A CLA with a contrast jet flow in cardiac CT has a high PPV for PFO detection, and its diagnostic performance is superior to that of a CLA alone.No potential conflict of interest relevant to this article was reported.MDPIActa Medica Okayama2077-038312152023Evidence for Hypoxia-Induced Shift in ATP Production from Glycolysis to Mitochondrial Respiration in Pulmonary Artery Smooth Muscle Cells in Pulmonary Arterial Hypertension5028ENSatoshiAkagiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKazufumiNakamuraDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMegumiKondoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoshiHirohataDepartment of Medical Technology, Graduate School of Health Sciences, Okayama UniversityHeiichiroUdonoDepartment of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityMikakoNishidaDepartment of Immunology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama UniversityYukihiroSaitoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasashiYoshidaDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruMiyoshiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiItoDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityBackground: The metabolic state of pulmonary artery smooth muscle cells (PASMCs) from patients with pulmonary arterial hypertension (PAH) is not well understood. In this study, we examined the balance between glycolysis and mitochondrial respiration in non-PAH-PASMCs and PAH-PASMCs under normoxia and hypoxia. Methods: We investigated the enzymes involved in glycolysis and mitochondrial respiration, and studied the two major energy-yielding pathways (glycolysis and mitochondrial respiration) by measuring extracellular acidification rate (ECAR) and cellular oxygen consumption rate (OCR) using the Seahorse extracellular flux technology. Results: Under both normoxia and hypoxia, the mRNA and protein levels of pyruvate dehydrogenase kinase 1 and pyruvate dehydrogenase were increased in PAH-PASMCs compared with non-PAH-PASMCs. The mRNA and protein levels of lactate dehydrogenase, as well as the intracellular lactate concentration, were also increased in PAH-PASMCs compared with non-PAH-PASMCs under normoxia. However, these were not significantly increased in PAH-PASMCs compared with non-PAH-PASMCs under hypoxia. Under normoxia, ATP production was significantly lower in PAH-PASMCs (59 } 5 pmol/min) than in non-PAH-PASMCs (70 } 10 pmol/min). On the other hand, ATP production was significantly higher in PAH-PASMCs (31 } 5 pmol/min) than in non-PAH-PASMCs (14 } 3 pmol/min) under hypoxia. Conclusions: There is an underlying change in the metabolic strategy to generate ATP production under the challenge of hypoxia.No potential conflict of interest relevant to this article was reported.VM Media SP. zo.o VM Group SKActa Medica Okayama1898-018X2932021The number of circulating CD34-positive cells is an independent predictor of coronary artery calcification progression: Sub-analysis of a prospective multicenter study423431ENKeishiIchikawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical SciencesKazuhiroOsawaDepartment of Cardiovascular Medicine, Japanese Red Cross Okayama HospitalTakashiMikiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical SciencesKunihisaKohnoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical SciencesYasushiKoyamaDepartment of Cardiology, Sakurabashi Watanabe HospitalHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Density and Pharmaceutical SciencesBackground: Decreases in circulating CD34-positive cells are associated with increases in cardiovascular events. We investigated the association between the number of CD34-positive cells and the progression of coronary artery calcification (CAC), a marker of atherosclerosis, in patients with hypercholesteremia under statin therapy in a sub-analysis of a multicenter study.<br>
Methods: In the principal study, patients with CAC scores of 1–999 were treated with pitavastatin. Measurement of CAC by non-enhanced computed tomography and a blood test were performed at baseline and at 1-year follow-up. Patients were divided into two groups: CAC progression (change in CAC score > 0) and non-progression. The number of circulating CD34-positive cells was counted using flow cytometry.<br>
Results: A total of 156 patients (mean age 67 years, 55% men) were included in this sub-analysis. CD34 positive cell numbers at baseline as a continuous variable was inversely correlated with annual change in the log-transformed CAC score (r = –0.19, p = 0.02). When patients were divided into high and low CD34 groups based on the median value of 0.8 cells/L, the adjusted change in CAC score in the low-CD34 group was significantly greater than that in the high-CD34 group (54.2% vs. 20.8%, respectively, p = 0.04). In multiple logistic analysis, a low CD34-positive cell number was an independent predictor of CAC progression, with an odds ratio of 2.88 (95% confidence interval 1.28–6.49, p = 0.01).<br>
Conclusions: Low numbers of CD34-positive cells are associated with CAC progression in patients with hypercholesterolemia under statin therapy. The number of CD34-positive cells may help to identify patients at increased cardiovascular risk.No potential conflict of interest relevant to this article was reported.Oxford University Press (OUP)Acta Medica Okayama2047-487328182021Incremental prognostic value of non-alcoholic fatty liver disease over coronary computed tomography angiography findings in patients with suspected coronary artery disease20592066ENKeishiIchikawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazuhiroOsawaDepartment of General Internal Medicine 3, Kawasaki Medical School General Medical CenterTakashiMikiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHironobuTodaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesMasashiYoshidaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKazufumiNakamuraDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesHiroshiMoritaDepartment of Cardiovascular Therapeutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical ScienceHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAims@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).<br>
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 2 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 2 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.<br>
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.Frontiers MediaActa Medica Okayama2297-055X102023In vivo tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging1261330ENYukihiroSaitoDepartment of Cardiovascular Medicine, Okayama University HospitalNaokoNoseMolecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToshihiroIidaDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityKaoruAkazawaDepartment of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakayukiKannoMolecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityYukiFujimotoMolecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityTakanoriSasakiOkayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical SciencesMasaruAkehiOkayama Medical Innovation Center, Faculty of Medicine, Dentistry and Pharmaceutical SciencesTakahiroHiguchiMolecular Imaging Project of RECTOR Program, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversitySatoshiAkagiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityMasashiYoshidaDepartment of Chronic Kidney Disease and Cardiovascular Disease, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityToruMiyoshiDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiItoDepartment of General Internal Medicine 3, Kawasaki Medical SchoolKazufumiNakamuraDepartment of Cardiovascular Medicine, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityIntroduction: Transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established.<br>
Methods: In this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as 125I, 18F-tetrafluoroborate (TFB), and 99mTc-pertechnetate (99mTcO4|), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs.<br>
Results: To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by 99mTcO4| single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of 125I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using 99mTcO4| SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells.<br>
Discussion: Such functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions.No potential conflict of interest relevant to this article was reported.WileyActa Medica Okayama2055-58221042023Association of perivascular fat attenuation on computed tomography and heart failure with preserved ejection fraction24472457ENTakahiroNishiharaDepartment of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityToruMiyoshiDepartment of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityMitsutakaNakashimaDepartment of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityKeishiIchikawaDepartment of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityYoichiTakayaDepartment of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityRieNakayamaDepartment of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityTakashiMikiDepartment of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityHiroshiItoDepartment of Cardiovascular Medicine, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama UniversityAims@Heart failure with a preserved ejection fraction (HFpEF) is associated with chronic inflammation. We aimed to investigate the association between pericoronary adipose tissue attenuation (PCATA) on coronary computed tomography angiography as a novel noninvasive marker of pericoronary inflammation and the presence of HFpEF. <br>
Methods and results@This retrospective study included 607 outpatients (median age, 65 years; 50% male) who underwent both echocardiography and coronary computed tomography angiography. Patients with obstructive coronary artery disease were excluded from this study. PCATA was compared between patients with and without HFpEF, which was diagnosed according to the Heart Failure Association (HFA)-PEFF score. PCATA was assessed at the proximal 40-mm segments of all three major coronary arteries on coronary computed tomography angiography. Patients with HFpEF had higher PCATA in all coronary arteries compared to the control participants: left anterior descending artery (LAD), -65.2 +/- 6.9 Hounsfield units (HU) vs. -68.1 +/- 6.7 HU; left circumflex artery (LCX), -62.7 +/- 6.8 HU vs. -65.4 +/- 6.6 HU; and right coronary artery (RCA), -63.6 +/- 8.5 HU vs. -65.5 +/- 7.7 HU (P < 0.01). Multivariate logistic regression analysis, including conventional risk factors, revealed that PCATA per standard deviation in the LAD (odds ratio [OR], 1.449; 95% confidence interval [CI], 1.152-1.823), LCX (OR, 1.634; 95% CI, 1.283-2.081), and RCA (OR, 1.388; 95% CI, 1.107-1.740) were independently associated with HFpEF. The association between PCATA and HFpEF was mostly consistent across various patient clinical characteristics. The left ventricular mass and left atrial volume index showed a mild correlation with LAD-PCATA (rho = 0.13 [P rho = 0.24 [P < 0.01]) and LCX-PCATA (rho = 0.16 [P rho = 0.23 [P < 0.01]). <br>
Conclusions@High PCATA score was significantly associated with the presence of HFpEF. Our results suggest that inflammation in the pericoronary artery adipose tissue is one of the underlying mechanisms of HFpEF.No potential conflict of interest relevant to this article was reported.Japan Atherosclerosis SocietyActa Medica Okayama1340-347830122023Enhanced Production of EPA-Derived Anti-Inflammatory Metabolites after Oral Administration of a Novel Self-Emulsifying Highly Purified EPA Ethyl Ester Formulation (MND-2119)19271949ENToruMiyoshiDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesSatokoNaoeMedical Affairs Department, Mochida Pharmaceutical Co., Ltd.HiroyukiWakabayashiMedical Affairs Department, Mochida Pharmaceutical Co., Ltd.TakashiYanoMedical Affairs Department, Mochida Pharmaceutical Co., Ltd.TakuyaMoriClinical Research Department, Mochida Pharmaceutical Co., Ltd.ShingoKandaClinical Development Planning and Management Department, Mochida Pharmaceutical Co., Ltd.MakotoAritaLaboratory for Metabolomics, RIKEN Center for Integrative Medical SciencesHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesAims: MND-2119 is a novel once-daily dose self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (EPA-E) and is approved as an antihyperlipidemia agent in Japan. It has improved absorption and achieves higher plasma EPA concentrations at Cmax than conventional EPA-E. In the JELIS trial, concomitant use of EPA-E with statin therapy significantly reduced atherosclerotic cardiovascular disease (ASCVD) risks. As a potential mechanism of action of EPA, endogenous formation of EPA-derived anti-inflammatory metabolites is receiving greater attention. This study aims to investigate the endogenous formation of EPA-derived anti-inflammatory metabolites following single and multiple administrations of MND-2119.<br>
Methods: Healthy adult male subjects were randomly assigned to a nonintervention (control) group, MND-2119 2-g/day group, MND-2119 4-g/day group, or EPA-E 1.8-g/day group for 7 days (N=8 per group). Plasma fatty acids and EPA-derived metabolites were evaluated. Peripheral blood neutrophils were isolated, and the production of EPA-derived metabolites from in vitro stimulated neutrophils was evaluated.<br>
Results: After single and multiple administrations of MND-2119 2 g/day, there were significant increases in plasma EPA concentration, 18-hydroxyeicosapentaenoic acid (18-HEPE), and 17,18-epoxyeicosatetraenoic acid compared with those of EPA-E 1.8 g/day. They were further increased with MND-2119 4 g/day administration. In neutrophils, the EPA concentration in the MND-2119 2-g/day group was significantly higher compared with that in the EPA-E 1.8-g/day group after multiple administration, and 18-HEPE production was positively correlated with EPA concentration. No safety issues were noted.<br>
Conclusions: These results demonstrate that MND-2119 increases the plasma and cellular concentrations of EPA and EPA-derived metabolites to a greater extent than conventional EPA-E formulations.No potential conflict of interest relevant to this article was reported.