Search

Previously, we showed that augmented O-linked N-acetylglucosaminylation (O-GlcNAcylation) mitigates cardiac remodeling in O-GlcNAc transferase-transgenic (Ogt-Tg) mice exposed to acute (2-week) intermittent hypoxia (IH) by suppressing nuclear factor of activated T cells (NFAT) and nuclear factor kappa B (NF-κB) via the O-GlcNAcylation of glycogen synthase kinase 3 beta (GSK-3β) and NF-κB p65. Because this effect is time dependent, we exposed Ogt-Tg mice to IH for 4 weeks (IH4W) in the present study. O-GlcNAcylation was significantly enhanced in Ogt-Tg mice vs. wild-type (WT) mice exposed to normoxia and IH4W. Total O-GlcNAcylation levels were significantly increased in WT and Ogt-Tg mice after IH4W vs. normoxia. After IH4W, Ogt-Tg mice displayed significantly exacerbated signs of cardiac hypertrophy and fibrosis in the right ventricles (RVs) but not the left ventricles (LVs). Echocardiography revealed IH4W-induced right ventricular dysfunction. Phosphorylated GSK-3β levels were increased in Ogt-Tg mice vs. WT mice after IH4W, whereas phosphorylated NF-κB p65 levels were unaffected. Mitophagy, which is associated with cardiac dysfunction, was increased in the RVs of Ogt-Tg mice after IH4W. Furthermore, the levels of phosphorylated dynamin-related protein 1 (p-Drp1) were significantly increased, and the expression of mitofusin-2 (MFN2) was significantly decreased. In human embryonic kidney cells, mitochondrial uncoupler-induced mitochondrial dysfunction was accelerated in Ogt-overexpressing cells. In addition to increasing the levels of phosphorylated Smad2, IH4W promoted cardiac fibrosis in the RVs of Ogt-Tg mice. Thus, augmented O-GlcNAcylation may aggravate IH4W-induced right ventricular dysfunction and remodeling by promoting hypertrophy, mitophagy, and fibrosis via GSK-3β inactivation, an increased p-Drp-1/MFN2 ratio, and Smad2 activation, respectively.

Aims To examine the effects of a 24-month treatment with ipragliflozin on carotid intima-media thickness (IMT) in type 2 diabetes patients. Methods and results In this multicenter, prospective, randomized, open-label, and blinded-endpoint investigator-initiated clinical trial, adults with type 2 diabetes and haemoglobin A1C (HbA1c) of 6.0–10.0% (42–86 mmol/mol) were randomized equally to ipragliflozin (50 mg daily) and non-sodium-glucose cotransporter-2 (SGLT2) inhibitor use of standard-care (control group) for type 2 diabetes and were followed-up to 24 months. The primary endpoint was the change in mean common carotid artery IMT (CCA-IMT) from baseline to 24 months. A total of 482 patients were equally allocated to the ipragliflozin (N = 241) and control (N = 241) groups, and 464 patients (median age 68 years, female 31.7%, median type 2 diabetes duration 8 years, median HbA1c 7.3%) were included in the analyses. For the primary endpoint, the changes in the mean CCA-IMT from baseline to 24 months were 0.0013 [95% confidence interval (CI), −0.0155–0.0182] mm and 0.0015 (95% CI, −0.0155–0.0184) mm in the ipragliflozin and control groups, respectively, with an estimated group difference (ipragliflozin-control) of −0.0001 mm (95% CI, −0.0191–0.0189; P = 0.989). A group difference in HbA1c change at 24 months was also non-significant between the treatment groups [−0.1% (95% CI, −0.2–0.1); P = 0.359]. Conclusion Twenty-four months of ipragliflozin treatment did not affect carotid IMT status in patients with type 2 diabetes recruited in the PROTECT study, relative to the non-SGLT2 inhibitor-use standard care for type 2 diabetes.

The number of patients on maintenance hemodialysis (HD) diagnosed with sarcopenia has been increasing through as individuals age. Recent focus is on the condition termed, "dynapenia," which reduces only muscle function, as opposed to sarcopenia, which reduces both muscle mass and function. However, the association between dynapenia and cardio-cerebrovascular (CV) events in patients undergoing HD is largely unknown. The purpose of this study was to evaluate whether sarcopenia and dynapenia are associated with the onset of CV events in patients undergoing HD. We retrospectively analyzed 342 patients undergoing HD between January and December 2018. Patients who underwent HD thrice per week for 3 months were included in the analysis. We adopted the Asian Working Group on Sarcopenia criteria for the diagnosis of sarcopenia and dynapenia. In this study, 244 patients undergoing HD were enrolled. The prevalence of sarcopenia was 38.5%. Sarcopenia was determined to be an independent contributor to CV events in patients undergoing HD. To investigate the clinical relevance of dynapenia in patients with HD, patients without sarcopenia were further divided into dynapenia and non-dynapenia groups. Among 150 patients without sarcopenia, 46 were diagnosed with dynapenia. In the Kaplan-Meier analysis, the rate of CV events was significantly different among the three groups in a stratified manner, with the highest rate in the sarcopenia group and the lowest rate in the non-sarco-dynapenia group. Both patients with sarcopenia and dynapenia had significantly increased CV events compared to those with non-sarco-dynapenia (HR 8.00; 95% CI 2.73-34.1; p 0.0001 vs. HR 4.85; 95% CI 1.28-23.0; p 0.02). Both sarcopenia and dynapenia resulted in significantly higher CV events than non-sarco-dynapenia in patients undergoing HD. Therefore, clinicians should evaluate muscle function in addition to muscle quantity to estimate CV events in patients undergoing HD.

研究グループは、大腿部の筋肉内脂肪が非虚血性心筋症による心不全の予後に影響を与えることを初めて明らかにしました。本研究成果により、大腿部の筋肉内脂肪を測定することで心不全の予後を推測できる可能性が示されました。皮下脂肪や内臓脂肪以外の脂肪組織のことを異所性脂肪と呼び、主なものとしては心臓周囲脂肪や筋肉内脂肪があります。異所性脂肪の一つである心臓周囲脂肪が狭心症や心筋梗塞といった冠動脈疾患や心房細動を引き起こすとの報告はありましたが、身体の他の部位の異所性脂肪が心不全に与える影響についての報告は今までほとんどありませんでした。大腿部の筋肉内脂肪が糖尿病など生活習慣病の発症に影響を与えているという報告は既にあったため、今回、大腿部の筋肉内脂肪が心不全患者の予後に関係するかを調査しました。本研究グループは、2017年9月から2020年1月に大阪公立大学医学部附属病院で、心機能が低下した心不全の精査目的に入院し冠動脈疾患が否定された連続93例を対象とし、CTで大腿部のスキャンを行い、筋肉量と筋肉内脂肪を測定して筋肉内脂肪比を算出しました。筋肉内脂肪比を中央値で2群に分類し、それぞれの群で心血管死もしくは心血管系の病気による予期しない入院の発生率に差があるか検討を行いました。その結果、筋肉内脂肪比が高い群の方が発生率が高く、筋肉内脂肪比が独立した予後規定因子であることが明らかになりました。, Skeletal muscle atrophy is an independent prognostic predictor for patients with chronic heart failure, and the concept of sarcopenia is drawing attention. Furthermore, the importance of not only muscle mass but also ectopic fat has been pointed out. However, ......

A 70-year-old man with severe interstitial pneumonia attributed to limited cutaneous systemic sclerosis was referred to our institution because of worsening dyspnea. High-resolution computed tomography did not show considerable progression compared with previous images, whereas transthoracic echocardiography showed severe right ventricular dysfunction. Oxygen saturation was decreased to 84% at room air. A blood test showed an increase in the plasma brain natriuretic peptide level (289.4 pg/mL). Right heart catheterization (RHC) showed a remarkably high mean pulmonary arterial pressure (mPAP) of 48 mmHg at room air. A vaso reactivity test using inhaled nitric oxide showed improvement of mPAP, pulmonary vascular resistance (PVR), and partial pressure of arterial oxygen. These findings suggested that the patient responded to pulmonary hypertension (PH)-targeted drugs. We then prescribed tadalafil 10 mg and inhaled iloprost 5 µg six times daily. Three weeks after initiating PH-targeted drugs, RHC indicated hemodynamic improvement similar to hemodynamic changes in the vaso reactivity test (mPAP: 28 mmHg; PVR: 4.2 W.U.). He was discharged with improved symptoms. Inhaled nitric oxide during RHC might be helpful to consider the treatment strategy when patients have PH comorbid systemic sclerosis and severe interstitial lung disease.

BACKGROUND Thickening of Achilles tendon (≥9 mm on radiography) is one of the diagnostic criteria for familial hypercholesterolemia (FH). Since FH is associated with premature coronary artery disease (CAD) including acute coronary syndrome (ACS), measurement of Achilles tendon thickness (ATT) is important for early diagnosis of FH. However, clinical significance of mild thickening of Achilles tendon in non-FH patients with CAD is unclear. The present study investigated the association of ATT with coronary lesion severity in early-onset ACS without clinically diagnosed FH. METHODS From outpatients who had a history of ACS under 60 years old, 76 clinically non-FH subjects (71 men and 5 women; mean age at the onset of ACS, 50.5 years) with maximum ATT of

研究グループは、TAVI施術者に対する基本チェックリストによるフレイルの評価が経カテーテル大動脈弁留置術(TAVI)後3年の総死亡の予測因子として有用であることを明らかにしました。本研究成果により、基本チェックリストがフレイルを簡便かつ客観的に評価し、適切な治療方針の決定に役立つと期待できます。フレイルの指標とTAVIとの関連性はこれまでに報告されていますが、それらの指標は検査を多く要するものや、簡便であっても客観性に欠けるものがあります。今回、本研究グループは、2016年1月から2020年12月に本学医学部附属病院でTAVIを施行した280例を対象とし、従来のフレイルの指標に加えて基本チェックリストによるフレイルの評価を行いました。その結果、基本チェックリストにより算出したフレイルの指標は、従来のフレイルの指標と比較し同等であり、生存時間分析でTAVI後3年の死亡の独立した因子であることが分かりました。また、基本チェックリストの総スコア(25点満点)で3群に分類して解析したところ、フレイル群(13～25点)でTAVI後3年の死亡が有意に高いことが分かりました。, Background: Frailty is a major risk factor for death and disability following transcatheter aortic valve implantation (TAVI). The Kihon checklist (KCL) is a simple self-reporting yes/no survey consisting of 25 questions and is used as a screening tool to identify frailty in the primary care setting. No clinical studies have focused on frailty calculated by the KCL in the TAVI cohort. We investigated the 3-year prognostic impact of frailty evaluated by the KCL in patients who underwent TAVI. ......

A 48-year-old woman without any medical history visited an outpatient clinic with a chief complaint of cough persisting for more than 1 year and was diagnosed with organizing pneumonia. Computed tomography showed wall thickening with luminal stenosis of the main branch vessels of the aorta, and a detailed examination including fluorodeoxyglucose-positron emission tomography revealed Takayasu arteritis. There have been some reports of combined organizing pneumonia in similar vasculitis cases, but Takayasu arteritis and organizing pneumonia have not been reported to be associated. This case can be referred to when considering the association of lung lesions with Takayasu arteritis.

The present study investigated the clinical value of myocardial contrast-delayed enhancement (DE) with multidetector computed tomography (MDCT) without iodine re-injection immediately after primary percutaneous coronary intervention (PCI) for predicting future cardiovascular events after acute myocardial infarction (AMI). We performed a prospective study in which 263 consecutive patients with first AMI successfully treated with primary PCI were enrolled. Sixty-four-slice MDCT without the re-injection of contrast medium was performed immediately after PCI. Myocardial DE was considered to be transmural when involving myocardial thickness ≥ 75% (Group A; n = 104), subendocardial (

Pulmonary arterial hypertension (PAH) is a progressive condition that frequently results in right ventricular (RV) remodeling. The objectives of this study are to investigate effects of rivaroxaban on RV remodeling in a rat model of PAH, created with Sugen5416 and chronic hypoxia, and the in vitro effects of rivaroxaban on human cardiac microvascular endothelial cells (HCMECs). To create the PAH model, male Sprague-Dawley rats were subcutaneously injected with Sugen5416 (20 mg/kg) and exposed to 2 weeks of hypoxia (10% O2), followed by 2 weeks of exposure to normoxia. The animals were then divided into 2 groups with or without administration of rivaroxaban (1.2 mg/kg/day) for a further 4 weeks. HCMECs were cultured under hypoxic conditions (37°C, 1% O2, 5% CO2) with Sugen5416 and with or without rivaroxaban. In the model rats, RV systolic pressure and Fulton index increased by hypoxia with Sugen5416 were significantly decreased when treated with rivaroxaban. In HCMECs, hypoxia with Sugen5416 increased the expression of protease-activated receptor-2 (PAR-2) and the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NF-κB), while treatment with rivaroxaban significantly suppressed the expression of these proteins. Rivaroxaban attenuated RV remodeling in a rat model of PAH by reducing ERK, JNK and NF-κB activation. Rivaroxaban has the possibility of providing additive effects on RV remodeling in patients with PAH.

BACKGROUND AND OBJECTIVES: Vitamin D receptor activators and calcimimetics (calcium-sensing receptor agonists) are two major options for medical treatment of secondary hyperparathyroidism. A higher serum calcification propensity (a shorter T(50) value) is a novel surrogate marker of calcification stress and mortality in patients with CKD. We tested a hypothesis that a calcimimetic agent etelcalcetide is more effective in increasing T(50) value than a vitamin D receptor activator maxacalcitol. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A randomized, multicenter, open-label, blinded end point trial with active control was conducted in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. Patients were randomly assigned to receive intravenous etelcalcetide 5 mg thrice weekly (etelcalcetide group) or intravenous maxacalcitol 5 or 10 µg thrice weekly (maxacalcitol group). The primary, secondary, and tertiary outcomes were changes in T(50) value, handgrip strength, and score of the Dementia Assessment Sheet for Community-Based Integrated Care System from baseline to 12 months, respectively. RESULTS: In total, 425 patients from 23 dialysis centers were screened for eligibility, 326 patients were randomized (etelcalcetide, n=167; control, n=159), and 321 were included in the intention-to-treat analysis (median age, 66 years; 113 women [35%]). The median (interquartile range) of T(50) value was changed from 116 minutes (interquartile range, 90–151) to 131 minutes (interquartile range, 102–176) in the maxacalcitol group, whereas it was changed from 123 minutes (interquartile range, 98–174) to 166 minutes (interquartile range, 127–218) in the etelcalcetide group. The increase in T(50) value was significantly greater in the etelcalcetide group (difference in change, 20 minutes; 95% confidence interval, 7 to 34 minutes; P=0.004). No significant between-group difference was found in the change in handgrip strength or in the Dementia Assessment Sheet for Community-Based Integrated Care System score. CONCLUSIONS: Etelcalcetide was more effective in increasing T(50) value than maxacalcitol among patients on hemodialysis with secondary hyperparathyroidism. There was no difference in handgrip strength or cognition between the two drugs. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: VICTORY; UMIN000030636 and jRCTs051180156

Background Subcutaneous implantable cardioverter–defibrillator (S-ICD) represents an efficient alternative to transvenous ICD in patients who do not require pacing. The intraoperative defibrillation test (DFT) is recommended during S-ICD implantation to confirm appropriate sensing and successful 65-J termination of induced ventricular fibrillation (VF). However, few cases of oversensing of noise inhibiting therapies have been reported. Case summary We report the case of a 50-year-old man who underwent S-ICD implantation for secondary prevention of sudden cardiac death. Immediately after S-ICD implantation, VF was induced using a 50-Hz burst; however, shock was not delivered owing to sustained noise on the electrogram in the primary vector. Therefore, an external rescue shock was needed at 150 J. We changed the sensing vector from primary to secondary and performed a second DFT. The S-ICD could deliver an appropriate shock and was able to successfully terminate VF without noise markers in the secondary vector. During the second DFT, one back-up pacing was delivered after the shock; the sensing vector then automatically switched from the secondary to the alternate vector. However, noise was observed in the alternate vector despite sinus rhythm restoration. Discussion The present case demonstrated that noise was recorded in two different vectors during DFT, possibly supporting the hypothesis that the muscle spasm of the diaphragm induced by the 50-Hz burst causes oversensing of noise by the S-ICD.

Eicosapentaenoic acid (EPA) has been reported to reduce cardiovascular risk in patients with hypertriglyceridemia. Although several mechanisms underlying the effects of EPA have been demonstrated, those responsible for its beneficial role in patients with hypertriglyceridemia without evidence of coronary artery disease (CAD) have not been fully elucidated. We sought to clarify the main factors associated with EPA administration that led to improved endothelial function.Forty-seven consecutive patients with mild hypertriglyceridemia (mean age, 59 ± 13 years) without evidence of CAD were prospectively enrolled and administered purified EPA (1800 mg/day). Forty-four patients who were not administered EPA were enrolled as age- and sex-matched controls. Clinical variables and flow-mediated dilation (FMD) were examined before and after 6 months of treatment. Univariate and multivariate regression analyses were performed between FMD changes and clinical variables.EPA treatment decreased triglyceride levels (from 224.6 ± 58.8 to 151.8 ± 54.5 mg/dl, p 0.001) and increased FMD (from 4.21% ± 1.91% to 6.21% ± 2.30%, p 0.001). Multivariate analysis showed that the change in FMD was associated with the baseline high-density lipoprotein cholesterol (HDL-C) level (β = -0.331, p = 0.027) and the change in EPA/arachidonic acid (AA) ratio (β = 0.301, p = 0.048).EPA treatment improved triglyceride levels and FMD in patients with mild hypertriglyceridemia and without evidence of CAD. The baseline HDL-C level and the change in EPA/AA ratio predicted FMD improvement. The beneficial effects of EPA on triglyceride-rich lipoproteins and vascular endothelium may help improve endothelial function.

Subcutaneous implantable cardioverter-defibrillator implantation is known to be a safe procedure. However, inappropriate lead insertion can lead to serious complications. We present a case where an inappropriate lead placement resulted in puncturing the lung parenchyma, and successful management of the lead-related pneumothorax through thoracoscopic lead removal and partial lung resection. (Level of Difficulty: Intermediate.), Graphical abstract, Subcutaneous implantable cardioverter-defibrillator implantation is known to be a safe procedure. However, inappropriate lead insertion can lead to serious…

The blood levels of atrial and brain natriuretic peptides (ANP and BNP) are both increased markedly in hemodialysis patients, but the kinetics of the two are not always parallel. The present study investigated the association of changes in ANP and BNP levels before and after dialysis with changes in cardiac function in hemodialysis patients. A total of 57 patients (mean age 64 years, 47 males and 10 females) on maintenance hemodialysis with sinus rhythm were enrolled. Blood samples were taken at the beginning and end of dialysis, and plasma levels of ANP and BNP were measured. Changes in cardiac function during dialysis were examined by echocardiography performed just before and after dialysis. Both plasma ANP and BNP concentrations decreased significantly after hemodialysis, but the rate of decrease in BNP [mean ± SD, 555 ± 503 to 519 ± 477 pg/mL (- 6.4%), P = 0.011] was much smaller than that in ANP [233 ± 123 to 132 ± 83 pg/mL (- 43.4%), P 0.001]. As for the relation to the changes in echocardiographic parameters before and after dialysis, the decrease in inferior vena cava diameter had a close correlation with the decrease in ANP (r = 0.528, P 0.001), but not BNP. In contrast, the decrease in left ventricular end-diastolic volume index was correlated only with the decrease in BNP (r = 0.297, P = 0.035). The peak velocity ratio of early diastolic to atrial filling decreased with preload reduction by dialysis, and its decrease was more strongly correlated with the decrease in BNP (r = 0.407, P = 0.002) than that in ANP (r = 0.273, P = 0.040). These results demonstrated that in hemodialysis patients, the decrease in plasma ANP by a single dialysis was essentially caused by blood volume reduction, while BNP decrease was mainly induced by the reduction of left ventricular overload. Our findings indicate that the kinetics of both peptides during dialysis are regulated by different cardiac and hemodynamic factors.

PURPOSE: To develop an artificial intelligence–based model to detect mitral regurgitation on chest radiographs. MATERIALS AND METHODS: This retrospective study included echocardiographs and associated chest radiographs consecutively collected at a single institution between July 2016 and May 2019. Associated radiographs were those obtained within 30 days of echocardiography. These radiographs were labeled as positive or negative for mitral regurgitation on the basis of the echocardiographic reports and were divided into training, validation, and test datasets. An artificial intelligence model was developed by using the training dataset and was tuned by using the validation dataset. To evaluate the model, the area under the curve, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were assessed by using the test dataset. RESULTS: This study included a total of 10 367 images from 5270 patients. The training dataset included 8240 images (4216 patients), the validation dataset included 1073 images (527 patients), and the test dataset included 1054 images (527 patients). The area under the curve, sensitivity, specificity, accuracy, positive predictive value, and negative predictive value in the test dataset were 0.80 (95% CI: 0.77, 0.82), 71% (95% CI: 67, 75), 74% (95% CI: 70, 77), 73% (95% CI: 70, 75), 68% (95% CI: 64, 72), and 77% (95% CI: 73, 80), respectively. CONCLUSION: The developed deep learning–based artificial intelligence model may possibly differentiate patients with and without mitral regurgitation by using chest radiographs. Keywords: Computer-aided Diagnosis (CAD), Cardiac, Heart, Valves, Supervised Learning, Convolutional Neural Network (CNN), Deep Learning Algorithms, Machine Learning Algorithms Supplemental material is available for this article. © RSNA, 2022

研究グループは、血管内視鏡で大腿膝窩動脈に観察される潰瘍性プラークで生じる血栓が膝下動脈の塞栓源であることを初めて明らかにしました。本研究成果は、下肢閉塞性動脈硬化症に適した薬物療法の決定に寄与できると期待されます。下肢閉塞性動脈硬化症の患者において、膝下動脈の閉塞狭窄病変の程度は予後と相関する重要な因子として知られています。近年の病理学的研究から上流からの血栓による塞栓が膝下動脈病変の形成機序の一つとして想定されていますが、血栓が生体内のどこで生じているのか未だ同定されていませんでした。そこで、本研究グループは、医学部附属病院の循環器内科において大腿膝窩動脈に対して経皮的下肢動脈形成術を施行した連続症例研究31例を対象とし、手技開始前に血管内視鏡を用いて膝下動脈の上流血管である大腿膝窩動脈を観察しました。その結果、血管内視鏡で潰瘍性プラークが観察された23人(74.2%)の患者のうち22人(95.7%)に血管壁に血栓像が観察され、これは潰瘍性プラークが観察されなかった群より高く(37.5%)、また、潰瘍性プラークは膝下動脈の閉塞狭窄の程度を示す指標(Angiographic runoff score)とも強い相関があることがわかりました。, Purpose: The aim of this study was to validate a hypothesis that there is a correlation between up-stream atherosclerosis in femoropopliteal arteries (FPA) assessed by angioscopy and poor angiographic runoff score (ARS). ……

Cholesterol crystals (CCs) are frequently found in high-risk plaques, such as thin-capped fibroatheromas. The purpose of this study was to investigate the associations of CCs, plaque morphologies, and post-stent optical frequency domain imaging (OFDI) findings with periprocedural cardiac troponin (cTn) elevation in patients treated with percutaneous coronary intervention (PCI). This study consists of 119 patients with stable coronary artery disease (CAD) with normal cTn levels who underwent OFDI-guided PCI. Periprocedural cTn elevation was defined as an elevation of cTn ≥ × 5 times the upper reference limit after PCI. Pre- and post-stent OFDI findings, including fibrous cap thickness (FCT), presence of CCs, and parameters for lipid and calcification were analyzed. A total of 37 (31%) patients were classified into the periprocedural cTn elevation group. Compared with lesions without CCs, lesions exhibiting CCs had thinner FCT, larger lipid arc, and longer lipid length, and were more likely to have irregular protrusion and in-stent thrombus (all p

INTRODUCTION The electrocardiograms (ECG) criteria to anchor the lead to the right ventricular septum have not been established. This study aimed to identify ECG criteria of pacing at the right ventricular mid septum (RVMS) and investigate whether the paced QRS duration (pQRSd) from the RVMS was narrow. METHODS AND RESULTS In 42 patients, ECG pacing at the basal anterior wall (BA), mid-anterior wall (MA), apex (AP), and mid septum (MS) was recorded. The pacing sites were validated by using right ventriculography and computed tomography. We estimated the ECG parameters and compared them among the four pacing sites. The combination of simple four paced-ECG parameters could reliably confirm the pacing at the RVMS. The area under the receiver-operating characteristics curve for the number of positive findings among the following: (a) positive QRS in lead aVL, (b) QRS notching in lead I, (c) precordial leads transition at less than V5, and (d) presence of isoelectric QRS in the inferior leads was 0.95 (95% confidence interval, 0.91-0.98) and the number of positive findings (≥3) had a sensitivity of 83.3% and a specificity of 93.7% for discriminating MS from the other sites. The pQRSd with three or more positive findings was significantly narrower than that with less than three positive findings (≥3: 137.4 ± 9.2 ms

Type 2 diabetes mellitus (T2DM) has been reported to be associated with cardiac remodeling. Although O-GlcNAcylation is known to be elevated in diabetic and ischemic hearts, the effects of O-GlcNAcylation on cardiac remodeling induced by intermittent hypoxia (IH), such as sleep apnea syndrome (SAS), remain unknown. To evaluate the effects, we induced IH in wild-type (WT) and transgenic O-GlcNAc transferase (Ogt-Tg) mice. Two weeks of IH increased O-GlcNAcylation in the heart tissues of both strains of mice, whereas O-GlcNAcylation in Ogt-Tg mice was significantly higher than that in WT mice under both normoxic and IH conditions. WT mice exhibited cardiac remodeling after IH, whereas cardiac remodeling was significantly attenuated in Ogt-Tg mice. Oxidative stress and apoptosis increased after IH in both strains of mice, whereas the rate of increase in these processes in Ogt-Tg mice was significantly lower than that in WT mice. To examine the mechanism of cardiac remodeling attenuation in Ogt-Tg mice after IH, the effects of O-GlcNAcylation on the activities of the master regulators nuclear factor of activated T cells (NFAT) and NF-κB were determined. The O-GlcNAcylation of GSK-3β, a negative regulator of NFAT, was significantly increased in Ogt-Tg mice, whereas the phosphorylation of GSK-3β was reciprocally reduced. The same result was observed for NF-κB p65. An in vitro reporter assay showed that the augmentation of O-GlcNAcylation by an O-GlcNAcase inhibitor suppressed NFAT and NF-κB promoter activity. These data suggest that augmented O-GlcNAcylation mitigates IH-induced cardiac remodeling by suppressing NFAT and NF-κB activities through the O-GlcNAcylation of GSK-3β and NF-κB p65.

BACKGROUND The implantation of leads in the right atrial septum (RAS) or the right ventricular septum (RVS) is technically challenging, and dislodgement occurs occasionally. This study aims to determine a predictor for the dislodgement of leads implanted in the RAS or RVS. METHODS This retrospective cohort study enrolled 137 consecutive patients who underwent the cardiac implantable electronic devices implantation, using active fixation leads in the RAS and RVS. We compared the pacing threshold, R- or P-wave amplitude, slew rate, and presence of the current of injury (COI) between dislodged and nondislodged leads. RESULTS We performed lead fixation for 74 and 125 times in the RAS and RVS, respectively. Atrial lead dislodgement occurred five times (6.8%) intraoperatively and five times (6.8%) postoperatively, whereas ventricular lead dislodgement occurred eight times (6.4%) intraoperatively and three times (2.4%) postoperatively. Although there were no lead parameters that showed a significant difference common to RAS lead and RVS lead, the presence of the COI was significantly different between nondislodged and dislodged leads in both the RAS and RVS (atrial leads: 57.8% vs 0%, P

Dipeptidyl peptidase-4 (DPP-4) inhibitors not only improve impaired glucose tolerance in diabetes, but also have pleiotropic extra-pancreatic effects such as preconditioning effect for myocardial ischemia-reperfusion injury. Here, we investigated the anti-remodeling effects of linagliptin, a DPP-4 inhibitor, by use of DPP-4-deficient rats.After the induction of myocardial infarction (MI), Fischer 344 rats with inactivating mutation of DPP-4 were orally administrated with a DPP-4 inhibitor, linagliptin (5 mg kg−1·day−1), or vehicle in drinking water for 4 weeks. Linagliptin did not affect hemodynamic status, body weight, and infarct size. In echocardiography, linagliptin tended to improve left ventricular (LV) systolic function, and significantly improved LV diastolic function, surprisingly. Interstitial fibrosis in marginal region and macrophage infiltration were significantly lower in the linagliptin group than those in the vehicle group. Fibrosis-related gene expressions, such as collagen I and transforming growth factor-β1 (TGF-β1), and inflammation-related expressions, such as macrophage chemotactic protein 1 and matrix metalloproteinase-2 (MMP-2), were significantly suppressed in marginal area of the linagliptin-treated rats compared with the vehicle rats. The TGF-β1 and MMP-2 protein levels were attenuated by linagliptin in DPP-4-deficient cardiac fibroblasts.Linagliptin can attenuate MI-induced cardiac remodeling via a DPP-4-independent pathway. Keywords: Dipeptidyl peptidase-4, Fibrosis, Left ventricular diastolic function, Macrophage, Myocardial infarction

Background Although careful monitoring of asymptomatic severe aortic stenosis (AS) is recommended to prevent missing the optimal timing of surgical or transcatheter aortic valve replacement, prophylactic treatment that could extend the asymptomatic period remains unknown. In a hypertensive population, high blood pressure (BP) measured at the doctor's office is known to be associated with B-type natriuretic peptide (BNP) level, a surrogate marker for symptomatic deterioration in AS. Little is known regarding the association between nocturnal BP variables and BNP in severe AS with preserved ejection fraction (EF). Methods and Results: The subjects consisted of 78 severe AS patients (mean age, 79±6 years) with preserved EF. Nocturnal BP was measured hourly using a home BP monitoring device. On multiple regression analysis, nocturnal mean systolic BP (SBP) remained independently associated with BNP after adjustment for age, sex, body mass index, estimated glomerular filtration rate, antihypertensive medication class, early diastolic mitral annular velocity, and left ventricular mass index (P=0.03), whereas diastolic BP (DBP) and variables of BP variability were not. Conclusions Higher nocturnal SBP rather than DBP or indices of BP variability was independently associated with BNP in AS patients with preserved EF. Intervention for nocturnal SBP may therefore extend the asymptomatic period and improve prognosis.