岡山医学会Acta Medica Okayama0030-155812122009急性心筋梗塞における冠微小循環障害の病態と治療戦略9198ENHiroshiItoNo potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6342009No-reflow Phenomenon in Patients with Acute Myocardial Infarction:Its Pathophysiology and Clinical Implications161168ENHiroshiItoReview10.18926/AMO/31817<p>For patients with acute myocardial infarction (MI), the immediate therapeutic goal is to establish the patency of the infarct-related artery. Prolonged myocardial ischemia, however, often breaks down the coronary microvasculature, and the flow to the infarct myocardium may be markedly reduced. This is called the no-reflow phenomenon. This phenomenon is important not solely because it correlates with infarct size but because it provides additional prognostic information. With recent advances in imaging modalities, the no-reflow phenomenon is observed more frequently than when clinical judgment alone is used. Patients with this phenomenon are associated with poor functional and clinical outcomes. Now, the no-reflow phenomenon can be a parameter with which to predict high-risk patients. The focus of reperfusion therapy has shifted toward the improvement of myocardial perfusion. The improvement of myocardial perfusion could promote the functional recovery of viable muscle and reduce infarct expansion, which is associated with favorable clinical outcomes. For this purpose, pharmacological interventions and catheter-based devices to retrieve embolic materials have been proposed. Advances in our understanding of the pathophysiology of microvascular dysfunction would aid the development of therapeutic strategies for its prevention and treatment.</p>No potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812412012慢性心不全治療ガイドライン7173ENKazufumiNakamuraHiroshiItoNo potential conflict of interest relevant to this article was reported.岡山医学会Acta Medica Okayama0030-155812532013外科的手術が不可能な慢性血栓塞栓性肺高血圧症に対する 内科的バルーン肺動脈形成術の新手法211216ENHirokiMizoguchiAikoOgawaMitsuruMunemasaHiroshiMikouchiHiroshiItoHiromiMatsubaraNo 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.Hindawi Publishing CorporationActa Medica Okayama20132013Dual Antiplatelet Therapy Can Be Discontinued at Three Months after Implantation of Zotarolimus-Eluting Stent in Patients with Coronary Artery DiseaseENTadashiWadaMakotoNakahamaHironobuTodaAtsuyukiWatanabeKatsushiHashimotoRitsukoTerasakaKazufumiNakamuraNobuyukiYamadaHiroshiItoDual antiplatelet therapy (DAPT) after percutaneous coronary intervention increases the risk of bleeding. We studied the safety and clinical outcomes of switching from DAPT to aspirin monotherapy at 3 months after ZES implantation. We retrospectively evaluated 168 consecutive patients with coronary artery disease who had been implanted with a ZES from June 2009 through March 2010. After excluding 40 patients according to exclusion criteria such as myocardial infarction, 128 patients were divided into a 3-month DAPT group (67 patients, 88 lesions) and a 12-month conventional DAPT group (61 patients, 81 lesions). Coronary angiographic followup and clinical followup were conducted at more than 8 months and at 12 months after ZES implantation, respectively. Minor and major bleeding events, stent thrombosis (ST), and major adverse cardiac events (MACE) (death, myocardial infarction, cerebrovascular accident, target lesion revascularization, and target vessel revascularization) were evaluated. There were no statistically significant differences in the incidences of ST and MACE between the two groups. The incidence of bleeding events was significantly lower in the 3-month group than in the 12-month group (1.5% versus 11.5%, ). DAPT can be safely discontinued at 3 months after ZES implantation, which reduces bleeding risk.No potential conflict of interest relevant to this article was reported.Public Library ScienceActa Medica Okayama1932-6203822013A Decreased Level of Serum Soluble Klotho Is an Independent Biomarker Associated with Arterial Stiffness in Patients with Chronic Kidney DiseaseENMasashiKitagawaHitoshiSugiyamaHiroshiMorinagaTatsuyukiInoueKeiichiTakiueAyuOgawaToshioYamanariYokoKikumotoHaruhito AdamUchidaShinjiKitamuraYoheiMaeshimaKazufumiNakamuraHiroshiItoHirofumiMakinoBackground: Klotho was originally identified in a mutant mouse strain unable to express the gene that consequently showed shortened life spans. In humans, low serum Klotho levels are related to the prevalence of cardiovascular diseases in community-dwelling adults. However, it is unclear whether the serum Klotho levels are associated with signs of vascular dysfunction such as arterial stiffness, a major determinant of prognosis, in human subjects with chronic kidney disease (CKD).
Methods: We determined the levels of serum soluble Klotho in 114 patients with CKD using ELISA and investigated the relationship between the level of Klotho and markers of CKD-mineral and bone disorder (CKD-MBD) and various types of vascular dysfunction, including flow-mediated dilatation, a marker of endothelial dysfunction, ankle-brachial pulse wave velocity (baPWV), a marker of arterial stiffness, intima-media thickness (IMT), a marker of atherosclerosis, and the aortic calcification index (ACI), a marker of vascular calcification.
Results: The serum Klotho level significantly correlated with the 1,25-dihydroxyvitamin D level and inversely correlated with the parathyroid hormone level and the fractional excretion of phosphate. There were significant decreases in serum Klotho in patients with arterial stiffness defined as baPWV >= 1400 cm/sec, atherosclerosis defined as maximum IMT >= 1.1 mm and vascular calcification scores of ACI>0%. The serum Klotho level was a significant determinant of arterial stiffness, but not endothelial dysfunction, atherosclerosis or vascular calcification, in the multivariate analysis in either metabolic model, the CKD model or the CKD-MBD model. The adjusted odds ratio of serum Klotho for the baPWV was 0.60 (p = 0.0075).
Conclusions: Decreases in the serum soluble Klotho levels are independently associated with signs of vascular dysfunction such as arterial stiffness in patients with CKD. Further research exploring whether therapeutic approaches to maintain or elevate the Klotho level could improve arterial stiffness in CKD patients is warranted.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.Acta Medica Okayama0735-109763202014Electrocardiographic Parameters and Fatal Arrhythmic Events in Patients With Brugada Syndrome21312138ENKojiTokiokaKengo F.KusanoHiroshiMoritaDaijiMiuraNobuhiroNishiiSatoshiNagaseKazufumiNakamuraKunihisaKohnoHiroshiItoTohruOheObjectives This study aimed to determine the usefulness of the combination of several electrocardiographic markers on risk assessment of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS).
Background Detection of high-/low-risk BrS patients using a noninvasive method is an important issue in the clinical setting. Several electrocardiographic markers related to depolarization and repolarization abnormalities have been reported, but the relationship and usefulness of these parameters in VF events are unclear.
Methods Baseline characteristics of 246 consecutive patients (236 men; mean age, 47.6 +/- 13.6 years) with a Brugada-type electrocardiogram, including 13 patients with a history of VF and 40 patients with a history of syncope episodes, were retrospectively analyzed. During the mean follow-up period of 45.1 months, VF in 23 patients and sudden cardiac death (SCD) in 1 patient were observed. Clinical/ genetic and electrocardiographic parameters were compared with VF/SCD events.
Results On univariate analysis, a history of VF and syncope episodes, paroxysmal atrial fibrillation, spontaneous type 1 pattern in the precordial leads, and electrocardiographic markers of depolarization abnormalities (QRS duration >= 120 ms, and fragmented QRS [f-QRS]) and those of repolarization abnormalities (inferolateral early repolarization [ER] pattern and QT prolongation) were associated with later cardiac events. On multivariable analysis, a history of VF and syncope episodes, inferolateral ER pattern, and f-QRS were independent predictors of documented VF and SCD (odds ratios: 19.61, 28.57, 2.87, and 5.21, respectively; p < 0.05). Kaplan-Meier curves showed that the presence/ absence of inferolateral ER and f-QRS predicted a worse/better prognosis (log-rank test, p < 0.01).
Conclusions The combination of depolarization and repolarization abnormalities in BrS is associated with later VF events. The combination of these abnormalities is useful for detecting high-and low-risk BrS patients.No potential conflict of interest relevant to this article was reported.Public Library ScienceActa Medica Okayama1932-6203972014Directed Differentiation of Patient-Specific Induced Pluripotent Stem Cells Identifies the Transcriptional Repression and Epigenetic Modification of NKX2-5, HAND1, and NOTCH1 in Hypoplastic Left Heart SyndromeENJunkoKobayashiMasashiYoshidaSuguruTaruiMasatakaHirataYusukeNagaiShingoKasaharaKeijiNaruseHiroshiItoShunjiSanoHidemasaOhThe genetic basis of hypoplastic left heart syndrome (HLHS) remains unknown, and the lack of animal models to reconstitute the cardiac maldevelopment has hampered the study of this disease. This study investigated the altered control of transcriptional and epigenetic programs that may affect the development of HLHS by using disease-specific induced pluripotent stem (iPS) cells. Cardiac progenitor cells (CPCs) were isolated from patients with congenital heart diseases to generate patient-specific iPS cells. Comparative gene expression analysis of HLHS- and biventricle (BV) heart-derived iPS cells was performed to dissect the complex genetic circuits that may promote the disease phenotype. Both HLHS- and BV heart-derived CPCs were reprogrammed to generate disease-specific iPS cells, which showed characteristic human embryonic stem cell signatures, expressed pluripotency markers, and could give rise to cardiomyocytes. However, HLHS-iPS cells exhibited lower cardiomyogenic differentiation potential than BV-iPS cells. Quantitative gene expression analysis demonstrated that HLHS-derived iPS cells showed transcriptional repression of NKX2-5, reduced levels of TBX2 and NOTCH/HEY signaling, and inhibited HAND1/2 transcripts compared with control cells. Although both HLHS-derived CPCs and iPS cells showed reduced SRE and TNNT2 transcriptional activation compared with BV-derived cells, co-transfection of NKX2-5, HAND1, and NOTCH1 into HLHS-derived cells resulted in synergistic restoration of these promoters activation. Notably, gain- and loss-of-function studies revealed that NKX2-5 had a predominant impact on NPPA transcriptional activation. Moreover, differentiated HLHS-derived iPS cells showed reduced H3K4 dimethylation as well as histone H3 acetylation but increased H3K27 trimethylation to inhibit transcriptional activation on the NKX2-5 promoter. These findings suggest that patient-specific iPS cells may provide molecular insights into complex transcriptional and epigenetic mechanisms, at least in part, through combinatorial expression of NKX2-5, HAND1, and NOTCH1 that coordinately contribute to cardiac malformations in HLHS.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X6932015Epoprostenol Therapy for Pulmonary Arterial Hypertension129136ENSatoshiAkagiKazufumiNakamuraHiromiMatsubaraAikoOgawaToshihiroSarashinaKentaroEjiriHiroshiItoReview10.18926/AMO/53519Pulmonary arterial hypertension (PAH) is characterized by elevation of pulmonary artery pressure caused by pulmonary vasoconstriction and vascular remodeling, which leads to right heart failure and death. Epoprostenol (prostaglandin I2) has a potent short-acting vasodilator property, and intravenous continuous epoprostenol is therefore used for treatment of PAH. Here we review evidence for the usefulness of intravenous continuous epoprostenol therapy in patients with PAH. Epoprostenol therapy is effective in idiopathic PAH patients and in patients with PAH associated with connective tissue disease, portal hypertension or congenital heart diseases, but it is not effective in patients with pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis. High-dose epoprostenol therapy markedly improved hemodynamics in some patients with PAH, possibly due to reverse remodeling of pulmonary arteries. This therapy has several side effects and complications such as headache, hypotension and catheter-related infections. Intravenous continuous epoprostenol is an effective treatment, but there are still some problems to be resolved.No potential conflict of interest relevant to this article was reported.Okayama University Medical SchoolActa Medica Okayama0386-300X7052016Feasibility of Repairing Defects Followed by Treatment with Pulmonary Hypertension-specific Drugs (Repair and Treat) in Patients with Pulmonary Hypertension Associated with Atrial Septal Defect: Study Protocol for Interventional Trial397400ENSatoshiAkagiDepartment 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 ScienceTeijiAkagiCardiac Intensive Care Unit, Okayama University HospitalKojiNakagawaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceYoichiTakayaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceToshihiroSarashinaDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceKentaroEjiriDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceHiroshiItoDepartment of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical ScienceClinical Study Protocols10.18926/AMO/54600A treatment strategy for patients with pulmonary hypertension (PH) and atrial septal defect (ASD) remains unclear. This study was designed to evaluate the effects of initial repair of ASD followed by treatment with PH-specific drugs in patients with PH and ASD. Eligible patients receive transcatheter ASD closure followed by treatment with bosentan and sildenafil. Right heart catheterization is performed at baseline and at 12, 24 and 48 weeks. The primary endpoint is change in pulmonary artery pressure and pulmonary vascular resistance from baseline to follow-up. This study should provide valuable information to establish a therapeutic strategy for PH and ASD.No potential conflict of interest relevant to this article was reported.