記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: 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.

DOI： 10.3390/jcdd10050193

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Exercise therapy following endovascular treatment (EVT) is important for patients with peripheral artery disease (PAD); however, continuous exercise therapy is difficult to be performed in clinical practice. This study aimed to investigate the association between the implementation of home-based exercise using pedometers after EVT and 1-year clinical outcomes. METHODS: This multicenter observational prospective cohort registry included patients with PAD complaining of intermittent claudication who underwent EVT for aortoiliac and/or femoropopliteal artery lesions between January 2016 and March 2019. Patients were instructed to perform home-based exercises using a specific pedometer after EVT. The study population was divided into good and poor recording groups according to the frequency of the pedometer measurements. The good recording group was defined as those who completed ≥50 % of the prescribed daily pedometer recording during the follow-up period. The poor recording group was defined as those with an inability to use a pedometer and/or who completed <50 % of the prescribed daily pedometer recordings. The primary outcome was 1-year major adverse events (MAE), defined as a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, target vessel revascularization, and major amputation of the target limb. RESULTS: The mean age was 74.4 years; 78 % were male. A total of 623 lesions were analyzed (58.7 % aortoiliac, 41.3 % femoropopliteal). At 1 year, a lower cumulative incidence of MAE was observed in the good recording group compared to that in the poor recording group [10/233 (4.3 %) vs. 35/267 (13.7 %) patients, respectively; p < 0.001]. Multivariate Cox regression analysis showed that patients in the good recording group had a lower hazard ratio for 1-year MAE (0.33; 95 % confidence interval, 0.16-0.68; p = 0.004) than that in the poor recording group. CONCLUSIONS: Good self-recording of pedometer measurements was associated with favorable prognosis in patients with PAD following EVT.

DOI： 10.1016/j.jjcc.2022.09.005

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.jacasi.2022.10.013

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Sodium-glucose cotransporter 2 inhibitors could reduce cardiovascular events in patients with heart failure irrespective of diabetes status. In this prespecified sub-analysis of randomised-controlled trial, we investigated the efficacy of luseogliflozin (2.5 mg daily), a sodium-glucose cotransporter 2 inhibitor, with that of voglibose (0.6 mg daily), an alpha-glucosidase inhibitor, on high-risk lipid profile and inflammatory markers in patients with type-2 diabetes and heart failure. Among the 157 patients studied, there were no significant differences in the mean malondialdehyde LDL or small-dense LDL cholesterol levels between the luseogliflozin and voglibose groups (percent change: 0.2% vs. - 0.6%, p = 0.93; - 1.7% vs. - 8.6%, p = 0.21) after 12 weeks in comparison to levels at the baseline. No significant difference was observed between the two groups in the adiponectin and high-sensitivity C-reactive protein levels after 12 weeks compared to the baseline levels (percent change, - 1.6% vs. - 4.0% and 22.5% vs. 10.0%; p = 0.52 and p = 0.55, respectively). In conclusion, in patients with type-2 diabetes and heart failure, compared to voglibose, luseogliflozin did not significantly improve the high-risk lipoprotein profile including malondialdehyde LDL and small-dense LDL cholesterol or the levels of inflammatory markers, including adiponectin and high-sensitivity C-reactive protein.Trial registration: Trial number: UMIN-CTR, UMIN000018395; Registered 23 July 2015; URL: https://www.umin.ac.jp/ctr/index.htm .

DOI： 10.1038/s41598-022-19371-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Dual-energy computed tomography (DECT) is a promising technique for the assessment of the lung perfused blood volume (LPBV) in the lung parenchyma. This study was performed to compare the LPBV by DECT of patients with pulmonary hypertension (PH) and controls and to evaluate the association between the LPBV and the perfusion ratio derived by lung perfusion scintigraphy. This study involved 45 patients who underwent DECT (25 patients with PH and 20 controls). We measured the total LPBV and distribution of the LPBV in each lung. The total LPBV was significantly lower in the PH group than the control group (38 ± 9 vs. 45 ± 8 HU, p = 0.024). Significant differences were observed between the LPBV of the upper lung of the PH and control groups (34 ± 10 vs. 47 ± 10, p = 0.021 and 37 ± 10 vs. 47 ± 8, p &lt; 0.001). A significant correlation was observed between the LPBV and the lung perfusion scintigraphy. A lower total LPBV and lower LPBV of the upper lung as detected by DECT might be specific findings of PH.

DOI： 10.3390/life12050684

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掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

There is a close relationship between diabetes mellitus and heart failure, and diabetes is an independent risk factor for heart failure. Diabetes and heart failure are linked by not only the complication of ischemic heart disease, but also by metabolic disorders such as glucose toxicity and lipotoxicity based on insulin resistance. Cardiac dysfunction in the absence of coronary artery disease, hypertension, and valvular disease is called diabetic cardiomyopathy. Diabetes-induced hyperglycemia and hyperinsulinemia lead to capillary damage, myocardial fibrosis, and myocardial hypertrophy with mitochondrial dysfunction. Lipotoxicity with extensive fat deposits or lipid droplets is observed on cardiomyocytes. Furthermore, increased oxidative stress and inflammation cause cardiac fibrosis and hypertrophy. Treatment with a sodium glucose cotransporter 2 (SGLT2) inhibitor is currently one of the most effective treatments for heart failure associated with diabetes. However, an effective treatment for lipotoxicity of the myocardium has not yet been established, and the establishment of an effective treatment is needed in the future. This review provides an overview of heart failure in diabetic patients for the clinical practice of clinicians.

DOI： 10.3390/ijms23073587

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Sodium glucose co-transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: This study was a post-hoc analysis of the MUSCAT-HF trial (UMIN000018395), a multicentre, prospective, open-label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed-effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group-difference -6.43% [95% confidence interval (CI): -9.11 to -3.74]}, at Week 12 [-8.73% (95%CI: -11.40 to -6.05)], and at Week 24 [-11.02% (95%CI: -13.71 to -8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log-transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019). CONCLUSIONS: Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF.

DOI： 10.1002/ehf2.13683

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Perioperative atrial fibrillation (POAF) after non-cardiac surgery is a risk factor for cardiovascular events including stroke and death. The aim of this subanalysis of the MAMACARI study, a multicenter randomized control study on the effectiveness of a bisoprolol transdermal patch for prevention of perioperative myocardial injury in high-risk patients undergoing non-cardiac surgery, was to identify the predictors of POAF after non-cardiac surgery in high-risk patients and to determine changes in blood pressure and heart rate during bisoprolol patch administration in the perioperative period. METHODS AND RESULTS: Patients aged over 60 years with hypertension and a high revised cardiac risk index (≥2) who were scheduled to undergo non-cardiac surgery were randomly assigned to a bisoprolol patch group (n = 120) or a control group (n = 120). We divided the patients into two groups: patients with POAF (POAF group; n = 16) and patients without POAF (non-POAF group; n = 206). Multivariate analysis showed that bisoprolol patch therapy (OR: 0.30, 95% CI: 0.092-0.978) and surgery time of 250 min or more (OR: 4.99, 95% CI: 1.37-18.2) were independently associated with POAF. Although systolic blood pressure did not differ significantly between the two groups throughout the perioperative period, treatment with a bisoprolol patch significantly reduced heart rate throughout the perioperative period compared with that in the control group. CONCLUSIONS: Low dose of a bisoprolol patch in the perioperative period was effective for prevention of POAF after non-cardiac surgery in high-risk patients, while long surgery time was an independent risk factor for POAF. It is expected that low dose of a bisoprolol patch can prevent POAF without causing hypotension.

DOI： 10.1016/j.jjcc.2021.05.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: This study aimed to investigate additional risk stratification benefits of hepatic steatosis (HS) concurrently assessed during coronary computed tomography angiography (CTA) in a large patient cohort with suspected stable coronary artery disease (CAD). METHODS AND RESULTS: In this prospective study, 1148 Japanese outpatients without a history of CAD who underwent coronary CTA for suspected stable CAD (mean age 64 ± 14 years) were included. HS, defined on CT as a hepatic-to-spleen attenuation ratio of <1.0, was examined just before the evaluation of adverse CTA findings, defined as obstructive and/or high-risk plaque. The major adverse cardiac events (MACE) were the composite of cardiac death, acute coronary syndrome, and late revascularization. The incremental predictive value of HS was evaluated using the global χ2 test and C-statistic. HS was identified in 247 (22%) patients. During a median follow-up of 3.9 years, MACE was observed in 40 (3.5%) patients. HS was significantly associated with MACE in a model that included adverse CTA findings (hazard ratio 4.01, 95% confidence interval 2.12-7.59, P < 0.001). By adding HS to the Framingham risk score and adverse CTA findings, the global χ2 score and C-statistic significantly increased from 29.0 to 49.5 (P < 0.001) and 0.74 to 0.81 (P = 0.026), respectively. In subgroup analyses in patients with diabetes mellitus and metabolic syndrome, HS had significant additive predictive value for MACE over the Framingham risk score and adverse CTA findings. CONCLUSION: In patients with suspected stable CAD, concurrent evaluation of HS during coronary CTA enables more accurate detection of patients at higher risk of MACE.

DOI： 10.1093/eurjpc/zwab120

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The receptor for advanced glycation end products (RAGE), a transmembrane receptor belonging to the immunoglobulin superfamily, is overexpressed in pulmonary artery smooth muscle cells (PASMCs) in patients with pulmonary arterial hypertension (PAH) and is implicated in the etiology of PAH. Recently, we reported that RAGE-aptamer, a short and single-stranded DNA directed against RAGE, inhibited an inappropriate increase in cultured PASMCs in PAH. The aim of this study was to determine the efficacy of RAGE-aptamer in monocrotaline-induced PAH in rats. METHODS AND RESULTS: Rats were assigned to either an untreated control group, a group that received continuous subcutaneous administration of RAGE-aptamer immediately after monocrotaline injection, or a group that received control-aptamer immediately after monocrotaline injection. All rats survived 21 days after injection of monocrotaline and control-aptamer or RAGE-aptamer. Injection of monocrotaline with continuous subcutaneous delivery of control-aptamer resulted in higher right ventricular systolic pressure compared with controls. This increase was attenuated by continuous subcutaneous delivery of RAGE-aptamer. The proportion of small pulmonary arteries with full muscularization was greater in the monocrotaline and control-aptamer group than in the control group. Continuous subcutaneous delivery of RAGE-aptamer significantly reduced the percentage of small pulmonary arteries with full muscularization. CONCLUSIONS: Continuous subcutaneous delivery of RAGE-aptamer suppresses development of monocrotaline-induced PAH in rats. Inhibition of RAGE ameliorates muscularization of small pulmonary arteries. Treatment with RAGE-aptamer might be a new therapeutic option for PAH.

DOI： 10.1016/j.jjcc.2020.12.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Oxidized high-density lipoprotein (oxHDL), unlike native HDL, is characterized by reduced cholesterol efflux capability and anti-inflammatory properties. The ratio of oxHDL to apolipoprotein A-I (oxHDL/apoAI) is a possible marker of dysfunctional HDL. The aim of this study was to evaluate the association between oxHDL/apoAI and coronary plaque characteristics that increase the likelihood of cardiovascular events as determined by coronary computed tomography (CT) angiography. METHODS: A total of 297 patients (mean age; 67 years, men; 63%) who underwent coronary CT angiography for suspected stable coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined by three characteristics: positive remodeling; low-density plaques; and spotty calcification. Significant stenosis was defined as a luminal narrowing of >70%. Serum concentrations of oxHDL were measured using an enzyme-linked immunosorbent assay. RESULTS: Patients with higher oxHDL/ApoAI showed significantly greater prevalence of HRP (p = 0.03) and significant stenosis (p < 0.01) compared with patients with low oxHDL/ ApoAI. The multivariate logistic analysis demonstrated that oxHDL/ApoAI significantly associated with the presence of HRP and significant coronary stenosis (p = 0.01 and < 0.01). In the follow-up study including 243 patients for a median period of 1.8 years, univariate cox regression analysis showed that oxHDL/ApoAI, HRP and significant stenosis were significant predictors of cardiovascular events. CONCLUSIONS: A high oxHDL/apoAI was associated with the presence of HRP and significant stenosis determined by coronary CT angiography, which can lead to cardiovascular events in patients with suspected stable CAD.

DOI： 10.1016/j.ijcard.2020.09.060

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Remote ischemic preconditioning (RIPC) is a promising strategy for protecting against ischemic reperfusion injury. This study is a secondary analysis of a randomized study that aimed to evaluate the effect of RIPC on the early increase in serum creatinine (SCr) following percutaneous coronary intervention (PCI), which is associ-ated with contrast-induced acute kidney injury. Patients with stable angina undergoing elective PCI were assigned to control, RIPC, and continuous infusion of nicorandil (nicorandil) groups. The endpoint of this study was the incidence of the early increase in SCr, a predictor of contrast-induced acute kidney injury, which was defined as either a > 20% or absolute increase by 0.3 mg/dl of SCr levels after 24 h of PCI. This study included 220 patients for whom a dataset of SCr values was available. The incidence of the early increase in SCr was significantly lower in the RIPC than in the control (1.3% vs 10.8%, p = 0.03) group, but was not significantly different between the nicorandil and control groups. In multivariate analysis, RIPC remained a significant fac-tor associated with a reduction in the incidence of early increase in SCr. RIPC reduces the incidence of early increase in SCr in patients with stable angina following elective PCI.

DOI： 10.18926/AMO/61433

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Risk stratification of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) has not been established. Coronary artery calcium score (CACS) and non-alcoholic fatty liver disease (NAFLD) are independently associated with cardiovascular events in T2DM patients. This study examined the incremental prognostic value of NAFLD assessed by non-enhanced computed tomography (CT) in addition to CACS and Framingham risk score (FRS) for cardiovascular events in T2DM patients. METHODS: This prospective pilot study included 529 T2DM outpatients with no history of cardiovascular disease who underwent CACS measurement because of suspected coronary artery disease. NAFLD was defined on CT images as a liver:spleen attenuation ratio < 1.0. Cardiovascular events were defined as cardiovascular death, nonfatal myocardial infarction, late coronary revascularization, nonfatal stroke, or hospitalization for heart failure. RESULTS: Among 529 patients (61% men, mean age 65 years), NAFLD was identified in 143 (27%). Forty-four cardiovascular events were documented during a median follow-up of 4.4 years. In multivariate Cox regression analysis, NAFLD, CACS, and FRS were associated with cardiovascular events (hazard ratios and 95% confidence intervals 5.43, 2.82-10.44, p < 0.001; 1.56, 1.32-1.86, p < 0.001; 1.23, 1.08-1.39, p = 0.001, respectively). The global χ2 score for predicting cardiovascular events increased significantly from 27.0 to 49.7 by adding NAFLD to CACS and FRS (p < 0.001). The addition of NAFLD to a model including CACS and FRS significantly increased the C-statistic from 0.71 to 0.80 (p = 0.005). The net reclassification achieved by adding CACS and FRS was 0.551 (p < 0.001). CONCLUSIONS: NAFLD assessed by CT, in addition to CACS and FRS, could be useful for identifying T2DM patients at higher risk of cardiovascular events.

DOI： 10.1186/s12933-020-01192-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background Effects of sodium-glucose cotransporter 2 inhibitors on reducing hospitalization for heart failure have been reported in randomized controlled trials, but their effects on patients with heart failure with preserved ejection fraction (HFpEF) are unknown. This study aimed to evaluate the drug efficacy of luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus and HFpEF. Methods and Results We performed a multicenter, open-label, randomized, controlled trial for comparing luseogliflozin 2.5 mg once daily with voglibose 0.2 mg 3 times daily in patients with type 2 diabetes mellitus suffering from HFpEF (left ventricular ejection fraction >45% and BNP [B-type natriuretic peptide] concentrations ≥35 pg/mL) in a 1:1 randomization fashion. The primary outcome was the difference from baseline in BNP levels after 12 weeks of treatment between the 2 drugs. A total of 173 patients with diabetes mellitus and HFpEF were included. Of these, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in BNP concentrations after 12 weeks from baseline between the 2 groups. The ratio of the mean BNP value at week 12 to the baseline value was 0.79 in the luseogliflozin group and 0.87 in the voglibose group (percent change, -9.0% versus -1.9%; ratio of change with luseogliflozin versus voglibose, 0.93; 95% CI, 0.78-1.10; P=0.26). Conclusion In patients with type 2 diabetes mellitus and HFpEF, there is no significant difference in the degree of reduction in BNP concentrations after 12 weeks between luseogliflozin and voglibose. Registration URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000018395.

DOI： 10.1161/JAHA.119.015103

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of transdermal β-blocker patches, which offer stable blood concentration and easy availability during operation, for prevention of perioperative myocardial injury (PMI) in high-risk patients.Methods and Results:In this randomized controlled trial, patients aged >60 years with hypertension and high revised cardiac risk index (≥2) undergoing non-cardiac surgery were randomly assigned to a bisoprolol patch or control group. Primary efficacy outcome was incidence of PMI, defined as postoperative high-sensitivity cardiac troponin T (hs-cTnT) >0.014ng/mL and relative hs-cTnT change ≥20%. Secondary efficacy outcomes were number of cardiovascular events and 30-day mortality. From November 2014 to February 2019, 240 patients from 5 hospitals were enrolled in this study. The incidence of PMI was 35.7% in the bisoprolol patch group and 44.5% in the control group (P=0.18). Incidence of major adverse cardiac events including non-critical myocardial infarction, strokes, decompensated heart failure and tachyarrhythmia was similar between the 2 groups. Tachyarrhythmia tended to be higher in the control group. There were no significant differences in safety outcomes including significant hypotension and bradycardia requiring any treatment between the 2 groups. CONCLUSIONS: Bisoprolol patches do not influence the incidence of PMI and cardiovascular events in high-risk patients undergoing non-cardiac surgery, but perioperative use of these patches is safe.

DOI： 10.1253/circj.CJ-19-0871

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Transition to pulmonary arterial hypertension (PAH)-specific drugs is considered in patients with PAH and chronic thromboembolic pulmonary hypertension who do not respond to combination therapy or who experience side effects to the combination drugs. Riociguat directly stimulates soluble guanylate cyclase independently of nitric oxide. Therefore, transition from a phosphodiesterase type 5 inhibitor (PDE5i), which requires nitric oxide to exert its effects, to riociguat might be effective. The length of time of washout periods for transition is important because haemodynamic instability sometimes occurs during these periods or during transition with no washout period. METHOD: We investigated the feasibility of transitioning from a PDE5i to riociguat without washout periods by monitoring haemodynamics under right heart catheterisation in six patients with PAH and one with chronic thromboembolic pulmonary hypertension who had already received dual- or triple-combination therapy. RESULTS: Reasons for transition were headache caused by a PDE5i in three patients, and an inadequate response to combination therapy in four. Transition was successful in all patients, with no haemodynamic instability observed. Pulmonary vascular resistance (from 797 ± 241 to 518 ± 230 dyne/s/cm-5) and systemic blood pressure (from 121 ± 13 to 100 ± 15 mmHg) were significantly reduced immediately after transition. There were no significant differences in the tricuspid regurgitation pressure gradient or systemic blood pressure during the post-transition and follow-up periods. Headaches caused by a PDE5i were diminished after transition to riociguat. CONCLUSIONS: Transition from a PDE5i to riociguat without a washout period is safe. This transition may be a viable option for patients with headaches caused by a PDE5i, or who have an inadequate response to combination therapy that includes a PDE5i.

DOI： 10.1016/j.hlc.2019.01.013

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Previous studies demonstrated that the incidence of atrial fibrillation (AF) was significantly increased when patients aged ≥40 years had surgical atrial septal defect (ASD) closure (sASD). However, limited information is available on such findings in transcatheter ASD closure (tASD). The purpose of this study was to investigate the incidence of newly developed AF after tASD in patients aged ≥40 years in whom preoperative AF or atrial flutter (AFL) had not been detected and to compare with the incidence after sASD. METHODS: The medical records of patients aged ≥40 years without a history of AF or AFL who underwent tASD (n = 281) or sASD (n = 24) were reviewed. Patients who had catheter ablation before the ASD closure were excluded. Patients with a patent foramen ovale were also excluded. The incidence of newly developed AF after ASD closure and the risk factors for that were evaluated statistically. RESULTS: Eleven patients had newly developed AF (5 in tASD and 6 in sASD) postoperatively including 6 persistent AF (3 each after tASD and sASD). The cumulative incidence of newly developed AF was 0.7% in tASD and 16.7% in sASD, and 2.7% and 20.8% at 1 and 5 years, respectively (p < 0.001). ASD diameter ≥30 mm and sASD were potential risk factors for newly developed AF after ASD closure and postoperative persistent AF. CONCLUSIONS: In patients aged ≥40 years without a history of AF or AFL, the incidence of newly developed AF after tASD closure was lower than that after sASD. A large ASD more than 30 mm diameter was a potential risk factor for development of AF even if it is closed by transcatheter procedure. Further long-term evaluation after tASD is required to clarify preventive benefit for new onset AF in adult ASD population.

DOI： 10.1016/j.jjcc.2020.01.008

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The waiting period for lung transplantation (LT) is approximately 3 years in Japan. The prognosis of patients with pulmonary arterial hypertension (PAH) awaiting LT is poor without LT. Patients at the present center often survive in the long term after registration for LT. The aim of this study was to elucidate why some patients survive in the long term by investigating changes in pulmonary artery pressure (PAP) after registration, and medication used.Methods and Results:This study involved 57 patients with PAH who were enrolled in a registry for LT at Okayama University Hospital. We divided patients into 3 groups according to outcome: LT (n=27); death without LT (n=21); and survival without LT (n=9). The median interval from PAH diagnosis to epoprostenol treatment was shorter in the survival group (58 days) than in the LT group (378 days) and death group (545 days). Eight patients in the survival group, 13 in the LT group, and 13 in the death group underwent right heart catheterization after registration. Percent change in mean PAP after registration was significantly greater in the survival group (-32%) than in the LT group (-13%) and death group (1%; P<0.01). CONCLUSIONS: Even after LT registration, patients who received epoprostenol infusion soon after diagnosis of PAH often had marked reduction in PAP and long-term survival without LT.

DOI： 10.1253/circj.CJ-19-0784

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

There are three critical pathways for the pathogenesis and progression of pulmonary arterial hypertension (PAH): the prostacyclin (prostaglandin I2) (PGI2), nitric oxide (NO), and endothelin pathways. The current approved drugs targeting these three pathways, including prostacyclin (PGI2), 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 (PGI2) 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.

DOI： 10.3390/ijms20235885

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記述言語：英語  

DOI： 10.1016/j.jjcc.2019.05.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a strong risk factor for coronary artery disease and heart failure, particularly heart failure with preserved ejection fraction (HFpEF). The aim of the ongoing MUSCAT-HF (It stands for Prospective Comparison of Luseogliflozin and Alpha-glucosidase on the Management of Diabetic Patients with Chronic Heart Failure and Preserved Ejection Fraction) trial is to evaluate the efficacy of luseogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, versus voglibose, an alpha-glucosidase inhibitor, using brain natriuretic peptide (BNP) as the index of therapeutic effect in T2DM patients with HFpEF. METHODS AND ANALYSIS: A total of 190 patients with T2DM and HFpEF (ejection fraction >45%) who are drug-naïve or taking any anti-diabetic agents will be randomised (1:1) to receive luseogliflozin 2.5 mg one time per day or voglibose 0.2 mg three times per day. The patients will be stratified by age (<65 years, ≥65 years), baseline haemoglobin A1c (<8.0%, ≥8.0%), baseline BNP (<100 pg/mL, ≥100 pg/mL), baseline renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2, <60 mL/min/1.73 m2), use of thiazolidine or not and presence or absence of atrial fibrillation and flutter at screening. After randomisation, participants will receive the study drug for 12 weeks in addition to their background therapy. The primary endpoint is the proportional change in baseline BNP after 12 weeks of treatment. The key secondary endpoints are the change from baseline in the ratio of early mitral inflow velocity to mitral annular early diastolic velocity, body weight and glycaemic control after 12 weeks of treatment. ETHICS AND DISSEMINATION: The study has been approved by the ethics committee and the patients will be included after informed consent. The results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000018395.

DOI： 10.1136/bmjopen-2018-026590

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Remote ischemic preconditioning (RIPC) is promising for preventing periprocedural myocardial damage (pMD) in patients undergoing percutaneous coronary intervention (PCI). However, the impact of RIPC on pMD on smokers is not well elucidated. The aim of this study was to investigate an association between tobacco smoking and RIPC on pMD in patients planning to undergo PCI. Methods: This study used data from a multicenter randomized controlled trial involving patients with stable angina who planned to undergo elective PCI. We analyzed data for 262 patients in the control (n = 133) and upper-limb RIPC (n = 129) groups, including 166 current or former smokers. The major outcome was the pMD incidence following PCI, with pMD defined as an elevated level of highly sensitive cardiac troponin T or a creatine kinase myocardial band 12 or 24 h after PCI. Results: The incidence of pMD was significantly lower in the upper-limb RIPC group than in the control group (28/83 patients [33.8%] vs. 43/83 patients [51.8%], respectively; p = 0.018). In a multiple logistic regression model, tobacco smoking was an independent predictor of interacting with and enhancing the effect of RIPC on reducing the incidence of pMD after PCI (regression coefficient, -0.4 [95% confidence interval, -0.74 to -0.082]; p = 0.015). Conclusions: Tobacco smoking may have a beneficial effect on RIPC against pMD after PCI.

DOI： 10.1016/j.ijcha.2018.12.005

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記述言語：英語  

BACKGROUND: Balloon pulmonary angioplasty (BPA) has become an alternative treatment for inoperable patients with chronic thromboembolic pulmonary hypertension. Lung injury (LI) is a major complication of BPA and may attenuate the benefits of BPA. Therefore, we conducted a retrospective study to evaluate the association between patient and procedural characteristics and LI in patients with chronic thromboembolic pulmonary hypertension. METHODS AND RESULTS: We reviewed 76 patients with chronic thromboembolic pulmonary hypertension who underwent BPA and multidetector computed tomography scanning pre- and post-BPA procedures. We performed BPA on 1247 vessels during 297 BPA procedures and reviewed 594 multidetector computed tomography scans. By comparing pre- and post-BPA multidetector computed tomography images, we diagnosed LI as follows: newly appeared ground-glass opacity, consolidation, and pleural effusion. LI was detected using multidetector computed tomography scans during 138 procedures (47%), and mechanical ventilation was required during 40 procedures (13%). Angiographic findings of extravasation with or without simultaneous clinical symptoms (BPA-related vascular injury) occurred during 50 procedures (17%). In mixed-effect logistic regression models, the BPA-related vascular injury was an independent predictor of LI after BPA, odds ratio, 20.1 (6.43-63.1). High mean pulmonary artery pressure before BPA procedure and BPA-related vascular injury were independent predictors of mechanical ventilation after BPA, odds ratio, 1.13 (1.03-1.24) and 10.8 (3.77-30.9), respectively. CONCLUSIONS: Vascular injury during BPA could be a triggering factor of LI after BPA, and its severity could be exacerbated by a high pulmonary artery pressure.

DOI： 10.1161/CIRCINTERVENTIONS.117.005884

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The effect of remote ischemic preconditioning (RIPC) on periprocedural myocardial damage (pMD) in patients undergoing percutaneous coronary intervention (PCI) is controversial. The aim of this study was to investigate the effect of RIPC or intravenous nicorandil on pMD following elective PCI in a subgroup of patients with complex coronary lesions from a multicenter randomized controlled trial.Methods and Results:Patients with stable angina who underwent elective PCI were assigned to 3 groups: control, upper-limb RIPC or intravenous nicorandil. The major outcome was pMD incidence following PCI, with pMD defined as an elevated level of high-sensitivity cardiac troponin T or creatine kinase myocardial band at 12 or 24 h after PCI. A total of 171 patients with complex coronary lesions (ACC-AHA coronary classification type B2 or C) were analyzed. The incidence of pMD following PCI was significantly lower in the RIPC group than in the control group (44.4% vs. 66.1%; P=0.023). The adjusted odds ratio (95% confidence interval) for pMD in the RIPC vs. the controls was 0.41 (0.18-0.94). The incidence of pMD in the nicorandil group was not significantly reduced compared with the control groups. CONCLUSIONS: This substudy suggested that RIPC prior to PCI prevented pMD in patients with complex coronary lesions. Further investigation in a multicenter prospective study is needed to confirm these results.

DOI： 10.1253/circj.CJ-17-1000

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Pulmonary artery (PA) dilatation is usually observed in patients with pulmonary hypertension (PH), but a PA aneurysm (PA diameter > 40mm) is rare. The difference between characteristics of patients with and those without progression of PA diameter remains poorly understood. We assessed the changes in PA diameter in patients with PH coexisting with and without a PA aneurysm. METHODS: We investigated the changes in PA diameter by multi-detector computed tomography performed twice with an interval of more than one year in 44 patients with PH. Seventeen patients had a PA aneurysm and 27 patients did not have a PA aneurysm at baseline. RESULTS: The median follow-up period was 3.6 years. All patients received medical or invasive treatment for PH. At baseline, main PA diameters were 52±15mm in patients with a PA aneurysm and 33±3mm in patients without a PA aneurysm. Mean PA pressure was higher in patients with a PA aneurysm than in those without a PA aneurysm (61±15mmHg vs. 51±16mmHg, p=0.04). At follow-up, mean PA pressure significantly decreased in both patients with a PA aneurysm (44±11mmHg) and patients without a PA aneurysm (41±18mmHg). Main PA diameter significantly increased in patients with a PA aneurysm (65±28mm, change ratio: 23.3%), while it did not increase in patients without a PA aneurysm (32±3mm, change ratio: -3.1%). CONCLUSIONS: PA dilatation progressed in patients with a PA aneurysm despite treatment of PH. The progression of PA dilatation is independent of reduction of PA pressure by PH treatment.

DOI： 10.1016/j.jjcc.2017.11.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Our previous study examined an effect of remote ischemic preconditioning (RIPC) or intravenous nicorandil on reduction of periprocedural myocardial injury (pMI) following percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD). We further investigated the effect of RIPC or nicorandil on pMI in older patients. METHODS: Patients with stable CAD who planned to undergo PCI were assigned to a 1:1:1 ratio to control, intravenous nicorandil, or upper-limb RIPC groups. This substudy analyzed patients aged >65 years (n = 282) from the principal cohort. The primary outcome was the incidence of pMI following PCI. We defined pMI as an elevated level of high-sensitive cardiac troponin T or creatine kinase myocardial band 12 or 24 hours after PCI. RESULTS: We found that pMI following PCI was significantly reduced in the nicorandil group compared with the control group (37.2% vs. 53.7%, multiplicity-adjusted p = 0.046), but not in the RIPC group compared with the control group (43.0% vs. 53.7%, multiplicity-adjusted p = 0.245). The adjusted odds ratios (95% confidence interval) for pMI in the RIPC and nicorandil groups versus the control group were 0.63 (0.34 to 1.16) and 0.51 (0.27 to 0.96), respectively. CONCLUSION: Intravenous nicorandil significantly reduces pMI following PCI in a subgroup of older patients with stable CAD. Phase 3 trials are required to validate our results. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000005607.

DOI： 10.1371/journal.pone.0194623

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Pulmonary vascular remodeling of pulmonary arterial hypertension (PAH) is characterized by an inappropriate increase of vascular cells. The receptor for advanced glycation end products (RAGE) is a type I single-pass transmembrane protein belonging to the immunoglobulin superfamily and is involved in a broad range of hyperproliferative diseases. RAGE is also implicated in the etiology of PAH and is overexpressed in pulmonary artery smooth muscle cells (PASMCs) in patients with PAH. We examined the role of RAGE in the inappropriate increase of PASMCs in patients with PAH. METHODS AND RESULTS: PASMCs were obtained from 12 patients with PAH including 9 patients with idiopathic PAH (IPAH) and 3 patients with heritable PAH (HPAH) (2 patients with BMPR2 mutation and one patient with SMAD9 mutation) who underwent lung transplantation. Western blot analysis and immunofluorescence staining revealed that RAGE and S100A8 and A9, ligands of RAGE, were overexpressed in IPAH and HPAH-PASMCs in the absence of any external growth stimulus. PDGF-BB (10 ng/mL) up-regulated the expression of RAGE in IPAH and HPAH-PASMCs. PAH-PASMCs are hyperplastic in the absence of any external growth stimulus as assessed by 3H-thymidine incorporation. This result indicates overgrowth characterized by continued growth under a condition of no growth stimulation in PAH-PASMCs. PDGF-BB stimulation caused a higher growth rate of PAH-PASMCs than that of non-PAH-PASMCs. AS-1, an inhibitor of TIR domain-mediated RAGE signaling, significantly inhibited overgrowth characterized by continued growth under a condition of no growth stimulation in IPAH and HPAH-PASMCs (P<0.0001). Furthermore, AS-1 significantly inhibited PDGF-stimulated proliferation of IPAH and HPAH-PASMCs (P<0.0001). CONCLUSIONS: RAGE plays a crucial role in the inappropriate increase of PAH-PASMCs. Inhibition of RAGE signaling may be a new therapeutic strategy for PAH.

DOI： 10.1371/journal.pone.0203046

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記述言語：英語  

DOI： 10.1016/j.ijcard.2017.04.075

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The effect of remote ischemic preconditioning (RIPC) and nicorandil on periprocedural myocardial injury (pMI) in patients with planned percutaneous coronary intervention (PCI) remains controversial. The aim of this randomized trial was to evaluate the effect of RIPC or nicorandil on pMI following PCI in patients with stable coronary artery disease (CAD) compared with a control group. METHODS: Patients with stable CAD who planned to undergo PCI were assigned to a 1:1:1 ratio to control, RIPC, or intravenous nicorandil (6mg/h). Automated RIPC was performed by a device, which performs intermittent arm ischemia through three cycles of 5min of inflation and 5min of deflation of a pressure cuff. The primary outcome was the incidence of pMI, determined by an elevation in high-sensitive troponin T or creatine kinase myocardial band at 12 or 24h after PCI. The secondary outcomes were ischemic events during PCI and adverse clinical events at 8months after PCI. RESULTS: A total of 391 patients were enrolled. The incidence of pMI following PCI was not significantly different between the control group (48.9%) and RIPC group (39.5%; p=0.14), or between the control group and nicorandil group (40.3%; p=0.17). There were no significant differences in ischemic events during PCI or adverse clinical events within 8months after PCI among the three groups. CONCLUSIONS: This study demonstrated moderate reductions in biomarker release and pMI by RIPC or intravenous nicorandil prior to the PCI consistently, but may have failed to achieve statistical significance because the study was underpowered.

DOI： 10.1016/j.ijcard.2017.02.028

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記述言語：英語  

DOI： 10.1016/j.jjcc.2017.02.002

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記述言語：日本語   出版者・発行元：(NPO)日本高血圧学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost) -incorporated nanoparticles and imatinib (a PDGF-receptor tyrosine kinase inhibitor) -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of pulmonary arterial hypertension (PAH) and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for the treatment of PAH.

DOI： 10.3390/jcm6050048

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

High diagnostic performance of noninvasive fractional flow reserve computed from CT (FFR-CT) was recently reported in prospective multicenter trials. The aims of this study were to evaluate the diagnostic accuracy of FFR-CT in clinical practice and to examine the lesion characteristics showing a mismatch between FFR-CT and invasive FFR. A total of 20 patients (29 vessels) with suspected coronary artery disease were included. All patients underwent invasive coronary angiography and invasive FFR according to coronary artery CT angiography (CCTA) findings. The same raw data used for CCTA were used to evaluate FFR-CT. Results from FFR-CT were compared with invasively measured FFR. A positive ischemia was defined as FFR <0.80. Analyses from three vessels in two patients were not evaluated because of severe calcification or motion artifacts. The diagnostic accuracy, sensitivity, and specificity of FFR-CT per-vessel basis were 81, 100, and 69 %, respectively. To find the reason for mismatch in positive ischemia, lesion characteristics determined with CCTA were compared between the matched group and the mismatched group. A significant difference in bifurcation lesions with positive remodeling was observed between the matched group and the mismatched group (p < 0.01). The high sensitivity of FFR-CT may provide an additional support to the use of CCTA, although particular attention should be paid when using FFR-CT in bifurcation lesions with positive remodeling.

DOI： 10.1007/s00380-016-0892-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Patients with pulmonary arterial hypertension (PAH) are currently treated with combination therapy of PAH-targeted drugs. Reverse right ventricular (RV) remodeling after lung transplantation (LTx) in patients with end-stage PAH despite combination therapy of PAH-targeted drugs has not been fully elucidated.Methods and Results:A total of 136 patients, including 32 with PAH, underwent LTx from 1998 to 2014. We enrolled 12 consecutive patients with PAH treated with combination therapy of PAH-targeted drugs who underwent LTx and retrospectively analyzed the temporal and serial changes in hemodynamics and echocardiography before LTx and at 3 and 12 months after LTx. Before LTx, the RV was markedly dilated with substantially reduced RV fractional area change (RVFAC). At 3 months after LTx, pulmonary artery pressure, pulmonary vascular resistance and RV stroke work index were significantly decreased, while left ventricular stroke work index was increased. RV size assessed by echocardiography also significantly decreased and RVFAC improved. At 12 months after LTx, RVFAC was further increased and RV wall thickness was decreased significantly. CONCLUSIONS: Although severe RV dysfunction and dilation were observed in patients with end-stage PAH despite combination therapy of PAH-targeted drugs, RV function and morphology were improved after reduction of RV pressure load by LTx.

DOI： 10.1253/circj.CJ-16-0838

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1161/CIRCIMAGING.116.005839

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

There were few reports regarding arrhythmias with idiopathic pulmonary arterial hypertension (IPAH). A 37-year-old woman was presented with a 6-year history of palpitations. She was diagnosed as IPAH at 25 years old and introduced continuous intravenous administration of PGI2 at 27 years old. Her electrocardiogram revealed paroxysmal supraventricular tachycardia (PSVT) and was referred for Catheter ablation. The electrophysiological study revealed dual pathway in AV and VA conduction. PSVT was induced by programmed atrial stimuli with jump up phenomenon under a small amount of isoproterenol. The tachycardia cycle length was from 460 ms to 560 ms, but earliest atrial potential was recorded at His and intra-atrial propagation was similar in any cycle lengths. The single-extra ventricular stimuli did not reset the tachycardia, so we diagnosed as common type AV nodal reentrant tachycardia. Fractionated potential so called slow pathway potential were recorded in broad posteroseptal area and junctional tachycardia was immediately obtained during the applications of radiofrequency current, but it was hard to eliminate the PSVT. After 12 deliveries of radiofrequency current, PSVT could not be induced by any programmed stimuli. © 2011, Japanese Heart Rhythm Society. All rights reserved.

DOI： 10.4020/jhrs.27.PJ2_074

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 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.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hypertrophic obstructive cardiomyopathy (HOCM) is cardiac hypertrophy of ventricular myocardium with left ventricular outflow tract obstruction. We report a pregnancy with HOCM after defibrillator implantation surgery. The patient was a 33-year-old nulligravida and was categorized as New York Heart Association class II. Her brain natriuretic peptide (BNP) level was 724.6 pg/dL at preconception. She received careful pregnancy management. However, because frequent uterine contractions were observed at 25 weeks and 6 days of pregnancy, she was hospitalized, and magnesium sulfate was started as a tocolytic agent. At 27 weeks and 5 days of pregnancy, she had respiratory discomfort and orthopnea with a sudden decrease in peripheral oxygen saturation. Cardiac ultrasonography showed a worsened condition of HOCM and her BNP level was 1418.0 pg/mL. We performed an emergent cesarean section and she delivered a boy weighing 999 g. The Apgar score was 8 and 9 points at 1 and 5 minutes, respectively. The mother's heart failure quickly improved after birth and she was discharged at 10 days postoperatively. Fluctuations in circulatory dynamics during pregnancy may sometimes exacerbate heart disease. Therefore, the risks should be fully explained and careful assessment of cardiac function should be performed during pregnancy in patients with severe HOCM.

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記述言語：英語  

DOI： 10.1016/j.jcin.2014.11.024

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pulmonary 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.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required.

DOI： 10.2147/VHRM.S50368

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記述言語：英語  

AIMS: Idiopathic/heritable pulmonary arterial hypertension (I/HPAH) carries a poor prognosis despite the therapeutic options available. Patient survival from Western countries has been reported, but data from Asia are scarce. MAIN METHODS: We retrospectively reviewed 56 patients with I/HPAH treated at a single referral center in Japan. Survival analyses were conducted using the Kaplan-Meier method with the log-rank test. Variables associated with survival were determined using a Cox proportional hazard model. KEY FINDINGS: There were 41 women (73%) and the mean age at the diagnosis was 32±17 years. Mean survival time from the diagnosis was 14.9±0.8 years (95% CI, 13.4-16.4 years), with 1-, 2-, 3-, 5- and 10-year survival rates of 98, 96, 96, 96 and 78%, respectively. In patients who underwent follow-up right-heart catheterization >3 months after initial catheterization, mean pulmonary arterial pressure (mPAP) was decreased significantly from 63±15 to 35±10 mm Hg with an improved cardiac index. Patients with high levels of brain natriuretic peptide (BNP) or low oxygen saturation at baseline showed worse survival. At follow-up, 98% of patients were on PAH-targeted drugs. WHO functional classes I and II, mPAP <42.5 mm Hg, cardiac index >2.5 L/min/m(2), BNP <52 pg/mL, and 6-min walk distance >347 m at follow-up were predictors of good prognosis in the univariate analysis. SIGNIFICANCE: The study revealed a long-term survival of Japanese patients with I/HPAH. Hemodynamic parameters improved significantly after treatment, which might be related to high prescription rates of PAH-targeted drugs. Multicenter studies are needed to reveal the prognostic factors for I/HPAH.

DOI： 10.1016/j.lfs.2014.01.077

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記述言語：英語  

DOI： 10.1016/j.jcin.2013.03.021

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記述言語：英語  

BACKGROUND: The long-term safety and efficacy of drug-eluting stents for patients with acute myocardial infarction (AMI) remain controversial. METHODS AND RESULTS: A total of 143 consecutive patients who presented between August 2004 and July 2006 with AMI and who underwent primary percutaneous coronary intervention (PCI) using sirolimus-eluting stents (SES), were compared with a historical control cohort of 129 consecutive patients who presented between August 2002 and July 2004 and who underwent primary PCI using bare metal stents (BMS). The rate of major adverse cardiovascular events at 3 years was significantly lower in the SES group than in the BMS group (20.3% vs. 33.1%, respectively; P=0.01). This reduction was mainly driven by a decrease in the rate of target vessel revascularization (12.3% vs. 22.4%, respectively; P=0.02). There was no significant difference in the rate of cardiovascular death (4.5% vs. 5.7%, respectively; P=0.67), non-fatal myocardial infarction (4.5% vs. 9.2%, respectively; P=0.16), coronary artery bypass grafting (2.3% vs. 2.5%, respectively; P=0.93), stroke (2.4% vs. 0.8%, respectively; P=0.35), and stent thrombosis (2.9% vs. 2.3%, respectively; P=0.80) between the 2 groups. CONCLUSIONS: SES can be used safely and effectively in patients with AMI.

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記述言語：英語  

BACKGROUND: The serum lipoprotein (a) [Lp(a)] level is genetically determined and remains consistent during a person's life. Previous cohort studies have reported that subjects with a high Lp(a) level are at high risk of cardiac events. METHODS AND RESULTS: This study consisted of 410 patients who underwent primary percutaneous coronary intervention within 24h of the onset of acute myocardial infarction (AMI). Lp(a) was measured 1 week after AMI and patients were divided into 2 groups based: high Lp(a) group (>40mg/dl, n=95) and low Lp(a) group (≤40mg/dl, n=315). A major adverse cardiac event (MACE) was defined as cardiac death, myocardial infarction and/or revascularization for new lesions. The incidence of MACE during 5 years was significantly higher in the high Lp(a) group than in the low Lp(a) group (34.7% vs. 16.5%, P<0.001). This difference was primarily driven by a higher incidence of new lesions requiring revascularization in the high Lp(a) group (31.6% vs. 15.2%, P<0.001). Multivariate analysis showed that Lp(a) was an independent predictor for MACE (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.31-2.06, P<0.001) and revascularization of a new lesion (OR 1.61, 95%CI 1.32-2.13, P<0.001). CONCLUSIONS: Lp(a) levels could predict the progression of the non-culprit coronary lesions after AMI.

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記述言語：英語  

AIM: Cardiopulmonary resuscitation (CPR) using extracorporeal life support (ECLS) for in-hospital cardiac arrest (IHCA) patients has been assigned a low-grade recommendation in current resuscitation guidelines. This study compared the outcomes of IHCA and out-of-hospital cardiac arrest (OHCA) patients treated with ECLS. METHODS: A total of 77 patients were treated with ECLS. Baselines characteristics and outcomes were compared for 38 IHCA and 39 OCHA patients. RESULTS: The time interval between collapse and starting ECLS was significantly shorter after IHCA than after OHCA (25 (21-43)min versus 59 (45-65)min, p<0.001). The weaning rate from ECLS (61% versus 36%, p=0.03) and 30-day survival (34% versus 13%, p=0.03) were higher for IHCA compared with OHCA patients. IHCA patients had a higher rate of favourable neurological outcome compared to OHCA patients, but the difference was not statistically significant (26% versus 10%, p=0.07). Kaplan-Meier analysis showed improved 30-day and 1-year survival for IHCA patients treated with ECLS compared to OHCA patients who had ECLS. However, multivariate stepwise Cox regression model analysis indicated no difference in 30-day (odds ratio 0.94 (95% confidence interval 0.68-1.27), p=0.67) and 1-year survival (0.99 (0.73-1.33), p=0.95). CONCLUSION: CPR with ECLS led to more favourable patient outcomes after IHCA compared with OHCA in our patient group. The difference in outcomes for ECLS after IHCA and OHCA disappeared after adjusting for patient factors and the time delay in starting ECLS.

DOI： 10.1016/j.resuscitation.2010.03.037

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記述言語：英語  

INTRODUCTION: The aim of the present study was to investigate the impact of the time interval from collapse to return of spontaneous circulation (CPA-ROSC) in cardiac arrest patients and the types of patients who will benefit from therapeutic hypothermia. METHODS: Four hundred witnessed adult comatose survivors of out-of-hospital cardiac arrest of cardiac etiology were enrolled in the study. The favorable neurological outcome was defined as category 1 or 2 on the five-point Pittsburgh cerebral performance scale at the time of hospital discharge. A matching process based on the propensity score was performed to equalize potential prognostic factors in the hypothermia and normothermia groups, and to formulate a balanced 1:1 matched cohort study. RESULTS: The rate of favorable neurological outcome was higher (P < 0.05) in the hypothermia group (n = 110) than in the normothermia group in patients with CPA-ROSC of 15 to 20 minutes (64% vs. 17%), 20 to 25 minutes (70% vs. 8%), 25 to 30 minutes (50% vs. 7%), 35 to 40 minutes (27% vs. 0%) and 40 to 45 minutes (29% vs. 2%). A similar association was observed in a propensity-matched cohort, but the differences were not significant. There was no significant difference in the rate of favorable neurological outcome between the hypothermia-matched group and the normothermia-matched group. In the patients whose CPA-ROSC was greater than 15 minutes, however, the rate of favorable neurological outcome was higher in the hypothermia-matched group than in the normothermia-matched group (27% vs. 4%, P < 0.001). In multivariate analysis, the CPA-ROSC was an independent predictor of favorable neurological outcome (every 1 minute: odds ratio = 0.89, 95% confidence interval = 0.85 to 0.92, P < 0.001). CONCLUSIONS: The CPA-ROSC is an independent predictor of neurological outcome. Therapeutic hypothermia is more beneficial in comatose survivors of cardiac arrest with CPA-ROSC greater than 15 minutes.

DOI： 10.1186/cc9225

PubMed

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：日本語   出版者・発行元：(有)科学評論社  

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記述言語：日本語   出版者・発行元：日本下肢救済・足病学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：日本成人先天性心疾患学会  

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記述言語：日本語   出版者・発行元：医歯薬出版(株)  

心不全において左室駆出率(LVEF)は予後に影響を与える重要な指標であることから、これまで心不全は大きく、(1)LVEFが低下している心不全(HFrEF)と、(2)LVEFが保持されている心不全(HFpEF)、に分類されてきた。一方で以前から、これら2つの分類の境界領域であるLVEF40〜49%のグループは疾患の特徴や治療に対する反応性という点で既存の2つのグループとの違いが指摘されていた。これを踏まえ、2016年にLVEF40〜49%のグループはLVEFが軽度低下した心不全(HFmrEF)としてあらたに分類された。HFmrEFはあらたな研究や治療対象として注目されているが、これまでの臨床研究ではHFpEFとして扱われており、いまだに十分なデータがないことから、その臨床像は明らかではない。本稿では、現時点で判明しているエビデンスをもとに、あらたな心不全分類の狙いから、HFmrEFの疾患概念、特徴、診断と治療、予後について論じる。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：日本語   出版者・発行元：日本下肢救済・足病学会  

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記述言語：日本語   出版者・発行元：(株)じほう  

＜Key Points＞わが国は心不全が爆発的に増加する"心不全パンデミック"時代を迎えることが予想されている。急性心不全とは何らかの原因により心機能が低下し、肺や腎臓、肝臓などの主要な臓器が循環不全を起こした状態である。急性心不全の診断と治療は身体所見や血液検査などの情報から総合的に判断して、病状に応じた治療を迅速に行うことが重要である。急性心不全の治療において薬物治療が果たす役割は大きいが、それのみでは対応が困難な場合には速やかに非薬物療法も用いて治療を行う。心不全治療において急性期から慢性期まで一貫して、多職種のチームで包括的に治療することが予後改善につながる。(著者抄録)

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：日本成人先天性心疾患学会  

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記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(株)最新医学社  

3系統の肺動脈性肺高血圧症に対する特異的治療薬は,基礎研究を経て臨床応用されている.これらについて最近も進行している基礎研究を含めて概説する.さらに,薬剤封入ナノ粒子を用いたドラッグデリバリーシステム(DDS)について紹介する.(著者抄録)

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：日本語   出版者・発行元：(株)日本臨床社  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本高血圧学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：日本語   出版者・発行元：医歯薬出版(株)  

高血圧症は心血管イベントのもっとも重要なリスクであるが、ほとんどの患者には自覚症状がない。そのため、患者そして医療従事者ともにそのリスクを実感できず、治療が手遅れになることも少なくない。われわれは、高血圧症の原因が生命予後を確実に悪化させる全身血管の動脈硬化であることを強く自覚しなければならない。動脈硬化の進行を評価するのに有用であるのが各種血管機能検査である。その検査から得られた各種指標は、いずれも患者の予後予測に有用であるが統一的な血管機能検査は存在しない。血管機能検査には評価する内容により多くの種類があり、それぞれ実臨床における役割も異なる。血管機能検査はともすれば余分な検査と誤解されやすいため、検査説明の段階で医療従事者および患者自身が検査の内容や有効性について理解しておくことが重要である。本稿では動脈硬化の病態生理から各種血管機能検査の特徴、高血圧診療への応用法について述べる。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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記述言語：日本語   出版者・発行元：(一社)日本超音波検査学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本超音波検査学会  

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その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2016&ichushi_jid=J03449&link_issn=&doc_id=20160601170205&doc_link_id=%2Fcw5jssng%2F2016%2F0041s1%2F0ce%2F5230-5230%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcw5jssng%2F2016%2F0041s1%2F0ce%2F5230-5230%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(NPO)日本高血圧学会  

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：(株)医学書院  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(株)先端医学社  

β遮断薬は交感神経系アドレナリン受容体のβ受容体を遮断することで陰性変時作用、陰性変力作用、レニン・アンジオテンシン・アルドステロン系(RAA系)抑制作用を発揮して降圧作用を示す。収縮不全による心不全に対してβ遮断薬は確立された治療であるが、その選択が重要である。生命予後改善効果が認められているのはβ1(心臓)選択性の高いビソプロロールとαβ遮断薬であるカルベジロールの2つのみである。最近、心房細動合併の収縮不全患者にβ遮断薬を導入しても、洞調律の患者と同様な予後改善効果は十分得られない可能性が指摘されている。昨年発表された米国高血圧合同委員会第8次報告(JNC-8)では、β遮断薬は高血圧に対する第一選択薬として推奨されていないが、高血圧は心不全の重要な基礎疾患であることは銘記すべきであると考える。収縮不全、左室肥大患者、冠動脈疾患を合併する患者、糖尿病やCKDを合併する患者では心不全予防のためにもβ遮断薬の適応を考慮するべきである。(著者抄録)

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記述言語：日本語   出版者・発行元：(株)文光堂  

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記述言語：日本語   出版者・発行元：(株)メジカルビュー社  

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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記述言語：日本語   出版者・発行元：(独)国立病院機構岡山医療センター  

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記述言語：日本語   出版者・発行元：(独)国立病院機構岡山医療センター  

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記述言語：日本語   出版者・発行元：(独)国立病院機構岡山医療センター  

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記述言語：日本語   出版者・発行元：(独)国立病院機構岡山医療センター  

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記述言語：日本語   出版者・発行元：(独)国立病院機構岡山医療センター  

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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記述言語：日本語   出版者・発行元：(株)メディカルレビュー社  

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J-GLOBAL

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：国立病院総合医学会  

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記述言語：日本語   出版者・発行元：(公社)日本超音波医学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本超音波検査学会  

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記述言語：日本語   出版者・発行元：(一社)日本呼吸器学会  

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記述言語：日本語   出版者・発行元：国立病院総合医学会  

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記述言語：日本語   出版者・発行元：(一社)日本老年医学会  

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記述言語：日本語   出版者・発行元：国立病院総合医学会  

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記述言語：日本語   出版者・発行元：国立病院総合医学会  

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記述言語：日本語   出版者・発行元：国立病院総合医学会  

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記述言語：日本語   出版者・発行元：ライフサイエンス出版(株)  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：英語   出版者・発行元：JAPANESE CIRCULATION SOC  

Web of Science

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記述言語：日本語   出版者・発行元：(一社)日本内科学会  

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記述言語：日本語   出版者・発行元：国立病院総合医学会  

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記述言語：日本語   出版者・発行元：国立病院総合医学会  

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記述言語：日本語   出版者・発行元：国立病院総合医学会  

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記述言語：日本語   出版者・発行元：国立病院総合医学会  

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記述言語：日本語   出版者・発行元：国立病院総合医学会  

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記述言語：日本語   出版者・発行元：(一社)日本脈管学会  

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

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記述言語：日本語   出版者・発行元：広島医学会  

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

74歳女性。感冒症状を主訴に近医を受診、胸部造影CTにて肺動脈内の腫瘤影が指摘され、血栓性肺塞栓症の疑いで、著者らの施設へ転院となった。来院時、経胸壁心臓超音波検査では表面がやや不整で、内部構造不均一な腫瘤が右室中隔に認められ、肺動脈内に突出し、肺動脈内は腫瘍側方に加速血流がみられた。また、MRIでは腫瘤はT1強調で筋肉と同等信号、T2強調では淡い高信号を示していた。以上、これらの所見により、本症例は右室腫瘍の肺動脈伸展と診断され、腫瘍摘出術を施行したところ、右室中隔から広基性にかけて4×3×8cmの腫瘍が認められ、腫瘍は肺動脈弁から肺動脈内まで伸展していた。尚、術後の病理検査結果は血管肉腫で、更に腫瘍塞栓による肺高血圧に加え、呼吸器関連肺炎を合併しており、患者は手術から28日目に死亡となった。

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記述言語：日本語   出版者・発行元：広島医学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

Web of Science

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記述言語：日本語   出版者・発行元：広島医学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：広島医学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

症例は23歳、男性。12歳時に失神し、てんかんとして他院に数年間の通院歴あり。机に座って仕事中、心肺停止状態となり、救急隊の到着時に心室細動を認め、電気的除細動が計2回施行されたが心拍は再開せず、当院に搬送された。来院後、心肺蘇生により心拍が再開し、冠動脈造影上は特記すべき異常を認めず、低体温療法を施行し、明らかな神経学的障害を認めない程度に回復した。心電図上、δ波を認め、電気生理学的検査を施行、左室のKent束に対して高周波カテーテルアブレーションを施行し、成功した。アセチルコリン負荷試験、ピルジカイニド負荷試験は陰性で、電気生理学的検査により心室細動・心室頻拍は誘発されなかった。特発性心室細動の可能性も否定しきれなかったが、本人の希望で植込み型除細動器(ICD)は移植せず、退院した。心肺停止の原因としてWPW症候群が考えられ、救命し、アブレーションのみ行い、ICDを移植せず経過をみた症例を経験したので報告する。(著者抄録)

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

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記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

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記述言語：日本語   出版者・発行元：(一社)日本不整脈心電学会  

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記述言語：日本語   出版者・発行元：広島医学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

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記述言語：日本語   出版者・発行元：(NPO)日本冠疾患学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：(一社)日本心臓病学会  

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記述言語：日本語   出版者・発行元：広島医学会  

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