The Effect of Antihypertensive Therapy on Skeletal Muscle Mass and Bone Mineral Density in Patients With End-Stage Kidney Disease.

OBJECTIVE: Sarcopenia and osteoporosis substantially influence health and lifespan. However, the variables affecting skeletal muscle mass (SMM) or bone mineral density (BMD) remain unknown. DESIGN AND METHODS: From August 1, 2018 to July 31, 2019, we conducted a single-center, observational cohort study with 291 Japanese adult patients on maintenance hemodialysis due to end-stage kidney disease, who had their femoral neck BMD measured using dual-energy X-ray absorptiometry. After 1-year follow-up, we measured annual changes of BMD (ΔBMD) and SMM (ΔSMM), which were calculated through a modified creatinine index (mg/kg/day) using age, sex, serum creatinine, and single-pooled Kt/V for urea. The factors associated with ΔSMM/ΔBMD or progressive loss of SMM/BMD, defined as ΔSMM/ΔBMD < 0 per year, respectively, were analyzed with multivariable, linear regression or logistic regression models. RESULTS: The median age of the patients was 66 years and 33% were female. Dialysis vintage and ß-blocker-use were inversely correlated to ΔSMM. In comparison to nonusers, ß-blockers users had 2.5-fold higher SMM loss odd ratios [95% confidence interval, 1.3-4.8]. The risk for SMM loss caused by ß-blockers was not increased in users of renin-angiotensin system inhibitors. The ΔBMD was negatively correlated to the usage of calcium channel blockers. The risk of developing osteosarcopenia, which was defined as annual loss of both SMM and BMD, increased in calcium channel blockers users. CONCLUSIONS: The use of ß-blockers is associated with an elevated risk of developing sarcopenia, whereas renin-angiotensin system inhibitors may minimize this effect in patients with end-stage kidney disease. Use of calcium channel blocker therapy was associated with a faster decline of BMD.

Deep learning-based model detects atrial septal defects from electrocardiography: a cross-sectional multicenter hospital-based study.

Background: Atrial septal defect (ASD) increases the risk of adverse cardiovascular outcomes. Despite the potential for risk mitigation through minimally invasive percutaneous closure, ASD remains underdiagnosed due to subtle symptoms and examination findings. To bridge this diagnostic gap, we propose a novel screening strategy aimed at early detection and enhanced diagnosis through the implementation of a convolutional neural network (CNN) to identify ASD from 12-lead electrocardiography (ECG). Methods: ECGs were collected from patients with at least one recorded echocardiogram at 3 hospitals from 2 continents (Keio University Hospital from July 2011 to December 2020, Brigham and Women's Hospital from January 2015 to December 2020, and Dokkyo Medical University Saitama Medical Center from January 2010 and December 2021). ECGs from patients with a diagnosis of ASD were labeled as positive cases while the remainder were labeled as negative. ECGs after the closure of ASD were excluded. After randomly splitting the ECGs into 3 datasets (50% derivation, 20% validation, and 30% test) with no patient overlap, a CNN-based model was trained using the derivation datasets from 2 hospitals and was tested on held-out datasets along with an external validation on the 3rd hospital. All eligible ECGs were used for derivation and validation whereas the earliest ECG for each patient was used for the test and external validation. The discrimination of ASD was assessed by the area under the receiver operating characteristic curve (AUROC). Multiple subgroups were examined to identify any heterogeneity. Findings: A total of 671,201 ECGs from 80,947 patients were collected from the 3 institutions. The AUROC for detecting ASD was 0.85-0.90 across the 3 hospitals. The subgroup analysis showed excellent performance across various characteristics Screening simulation using the model greatly increased sensitivity from 80.6% to 93.7% at specificity 33.6% when compared to using overt ECG abnormalities. Interpretation: A CNN-based model using 12-lead ECG successfully identified the presence of ASD with excellent generalizability across institutions from 2 separate continents. Funding: This work was supported by research grants from JST (JPMJPF2101), JSR corporation, Taiju Life Social Welfare Foundation, Kondou Kinen Medical Foundation, Research fund of Mitsukoshi health and welfare foundation, Tokai University School of Medicine Project Research and Internal Medicine Project Research, Secom Science and Technology Foundation, and Grants from AMED (JP23hma922012 and JP23ym0126813). This work was partially supported by One Brave Idea, co-funded by the American Heart Association and Verily with significant support from AstraZeneca and pillar support from Quest Diagnostics.

De-escalation of Oxygen Therapy and Medication in Patients With Chronic Thromboembolic Pulmonary Hypertension After Balloon Pulmonary Angioplasty.

BACKGROUND: There is no consensus on the adjustment of home oxygen therapy (HOT) and pulmonary hypertension (PH)-specific medications after balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to examine the status of de-escalation and discontinuation of HOT and PH-specific medications post-BPA and clarify its effect on hemodynamics, biomarkers, and long-term outcomes. METHODS: From November 2012 to May 2018, 135 consecutive patients with CTEPH who underwent BPA at a single university hospital were enrolled (age, 63.5 ± 13.5 years; World Health Organization functional class (WHO-FC) II, III, IV; 34, 92, 9). RESULTS: The mean pulmonary arterial pressure decreased from 37.7 ± 11.3 to 20.4 ± 5.1 mm Hg 1 year post-BPA (P < 0.01). The proportion of patients who required HOT and combination medical therapy (≥ 2 PH-specific medications) decreased 1 year post-BPA (from 58.5% to 7.4% and from 40.0% to 10.4%, respectively). Baseline factors influencing the requirement of HOT and combination medical therapy post-BPA were almost identical (ie, lower exercise capacity and pulmonary diffusion capacity and worse hemodynamics). Regardless of their discontinuation, the improved hemodynamics, functional capacity (WHO-FC), and biomarkers (B-type natriuretic peptide and high-sensitivity troponin T) were almost maintained, and no adverse 1-year clinical outcomes (all-cause death and PH-related hospitalization) were observed. CONCLUSIONS: Most patients with CTEPH discontinued HOT and PH-specific combination medical therapy post-BPA, which was not associated with the deterioration of hemodynamics, functional capacity, or biomarkers. No long-term adverse outcomes were observed.

Development of non-bias phenotypic drug screening for cardiomyocyte hypertrophy by image segmentation using deep learning.

The number of patients with heart failure and related deaths is rapidly increasing worldwide, making it a major problem. Cardiac hypertrophy is a crucial preliminary step in heart failure, but its treatment has not yet been fully successful. In this study, we established a system to evaluate cardiomyocyte hypertrophy using a deep learning-based high-throughput screening system and identified drugs that inhibit it. First, primary cultured cardiomyocytes from neonatal rats were stimulated by both angiotensin II and endothelin-1, and cellular images were captured using a phase-contrast microscope. Subsequently, we used a deep learning model for instance segmentation and established a system to automatically and unbiasedly evaluate the cardiomyocyte size and perimeter. Using this system, we screened 100 FDA-approved drugs library and identified 12 drugs that inhibited cardiomyocyte hypertrophy. We focused on ezetimibe, a cholesterol absorption inhibitor, that inhibited cardiomyocyte hypertrophy in a dose-dependent manner in vitro. Additionally, ezetimibe improved the cardiac dysfunction induced by pressure overload in mice. These results suggest that the deep learning-based system is useful for the evaluation of cardiomyocyte hypertrophy and drug screening, leading to the development of new treatments for heart failure.

The complement C3-complement factor D-C3a receptor signalling axis regulates cardiac remodelling in right ventricular failure.

Failure of the right ventricle plays a critical role in any type of heart failure. However, the mechanism remains unclear, and there is no specific therapy. Here, we show that the right ventricle predominantly expresses alternative complement pathway-related genes, including Cfd and C3aR1. Complement 3 (C3)-knockout attenuates right ventricular dysfunction and fibrosis in a mouse model of right ventricular failure. C3a is produced from C3 by the C3 convertase complex, which includes the essential component complement factor D (Cfd). Cfd-knockout mice also show attenuation of right ventricular failure. Moreover, the plasma concentration of CFD correlates with the severity of right ventricular failure in patients with chronic right ventricular failure. A C3a receptor (C3aR) antagonist dramatically improves right ventricular dysfunction in mice. In summary, we demonstrate the crucial role of the C3-Cfd-C3aR axis in right ventricular failure and highlight potential therapeutic targets for right ventricular failure.

Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan.

BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

DOCK8-expressing T follicular helper cells newly generated beyond self-organized criticality cause systemic lupus erythematosus.

Pathogens including autoantigens all failed to induce systemic lupus erythematosus (SLE). We, instead, studied the integrity of host's immune response that recognized pathogen. By stimulating TCR with an antigen repeatedly to levels that surpass host's steady-state response, self-organized criticality, SLE was induced in mice normally not prone to autoimmunity, wherein T follicular helper (Tfh) cells expressing the guanine nucleotide exchange factor DOCK8 on the cell surface were newly generated. DOCK8+Tfh cells passed through TCR re-revision and induced varieties of autoantibody and lupus lesions. They existed in splenic red pulp and peripheral blood of active lupus patients, which subsequently declined after therapy. Autoantibodies and disease were healed by anti-DOCK8 antibody in the mice including SLE-model (NZBxNZW) F1 mice. Thus, DOCK8+Tfh cells generated after repeated TCR stimulation by immunogenic form of pathogen, either exogenous or endogenous, in combination with HLA to levels that surpass system's self-organized criticality, cause SLE.

Reduction of Atrial Septal Defect Size After Catheter Ablation for Atrial Tachyarrhythmia and Its Predictive Factors.

The prevalence of atrial tachyarrhythmia is high in patients with atrial septal defect (ASD), and catheter ablation (CA) is often performed before percutaneous ASD closure. We aimed to clarify the effect of CA on the ASD size. We analysed 16 patients with secundum ASD who had a history of CA for atrial tachyarrhythmia and underwent ASD size evaluation before and after CA. The size of ASD significantly decreased after CA. Younger age and lower tricuspid regurgitation pressure gradients and pulmonary arterial systolic pressures were associated with size reduction. These factors are crucial for making strategies of percutaneous ASD closure.

La prévalence de la tachyarythmie auriculaire est élevée chez les patients qui présentent une communication interauriculaire (CIA), et l'on pratique souvent une ablation par cathéter avant la fermeture percutanée de la CIA. Notre objectif consistait à éclaircir l'effet de l'ablation par cathéter sur la taille de la CIA. Pour ce faire, nous avons analysé 16 patients présentant une CIA de type ostium secundum, ayant déjà subi une ablation par cathéter et chez qui la taille de la CIA a été évaluée avant et après l'intervention. La taille de la CIA a diminué de manière significative après l'ablation par cathéter. Les facteurs associés à la réduction de la taille de la communication comprennent un âge plus jeune, des gradients de pression plus faibles pour l'insuffisance tricuspidienne et une pression artérielle systolique moins élevée. Il est crucial de tenir compte de ces facteurs lors de l'établissement d'une stratégie pour la fermeture percutanée d'une CIA.

Predictors of New-Onset Atrial Tachyarrhythmias After Transcatheter Atrial Septal Defect Closure in Adults.

BACKGROUND: New-onset atrial tachyarrhythmia (ATA) often develops after atrial septal defect (ASD) closure. Its development raises some potential concerns such as stroke and bleeding complications caused by anticoagulant therapy and limited access to the left atrium for catheter ablation. Although it is essential to identify the risk factors of new-onset ATA, few studies have examined these factors. This study investigated unknown risk factors for the development of new-onset ATA after transcatheter ASD closure in patients without a history of ATA. METHODS: A total of 238 patients without a history of ATA, aged ≥18 years and who underwent transcatheter ASD closure at the current hospital were reviewed. Patient characteristics were compared between the groups with and without new-onset ATA. The factors associated with new-onset ATA were examined using univariate and multivariable analyses. RESULTS: Thirteen (13) (5.5%) patients experienced ATA during follow-up (mean, 21±14 months). Compared with patients without new-onset ATA, patients with new-onset ATA were older (48±18 vs 66±11 years; p<0.001) and had high brain natriuretic peptide (BNP) levels (36±36 vs 177±306 pg/mL; p<0.001). On multivariable analysis, BNP ≥40 pg/mL before ASD closure was associated with new-onset ATA after adjusting for age (OR, 4.91; 95% CI, 1.22-19.8; p=0.025). CONCLUSION: Patients with BNP levels >40 pg/mL before transcatheter ASD closure may have a higher risk of developing new-onset ATA.

Relationship between Cyst Fluid Concentrations of Iron and Severity of Dysmenorrhea in Patients with Ovarian Endometrioma.

OBJECTIVES AND DESIGN: Endometriosis-related pain can be caused by anatomical distortions as well as environmental factors such as inflammation and oxidative stress. The aim of this study is to investigate the relationship between the severity of dysmenorrhea in patients with ovarian endometrioma (OMA) and cyst fluid (CF) concentrations of irons, including total iron, heme iron, and free iron. METHOD: Eighty-three patients who were histologically diagnosed with OMA were enrolled in the Department of Gynecology, Nara Medical University Hospital, between 2013 and 2019. The patients were divided into 4 groups according to the severity of dysmenorrhea: no pain, mild, moderate, and severe. Iron concentration was measured by the inductively coupled plasma optical emission spectrometry method. RESULTS: There were no significant differences among the 4 groups in variables such as age at diagnosis, preoperative CA125, preoperative CA19-9, cyst size, and tumor laterality (unilateral or bilateral). There was a positive correlation between the severity of dysmenorrhea and total iron (p < 0.001) and heme iron (p = 0.016) concentrations. Multiple regression analyses revealed that the CF concentration of total iron (hazard ratio 18.75, 95% confidence interval: 2.26-155.35, p = 0.007) was a significant independent variable associated with the severity of dysmenorrhea. A receiver operating characteristic curve analysis showed that a total iron exceeding 290.8 mg/L was associated with severe dysmenorrhea with a sensitivity of 90.9% and a specificity of 65.7%. LIMITATIONS: This study excluded patients with adenomyosis, superficial endometriosis, or deep endometriosis, resulting in a smaller number of cases. Iron levels could not be compared to the endometriosis stage using the r-ASRM score. CONCLUSIONS: There is no clear evidence that iron predicts the severity of endometriosis-related pain. However, iron may be closely associated with dysmenorrhea.

Nonhormonal Treatment for Endometriosis Focusing on Redox Imbalance.

The aim of this review is to investigate the oxidant/antioxidant status and its regulatory mechanisms in patients with endometriosis and to summarize the antioxidant therapy as an alternative to hormonal therapy for endometriosis. Each keyword alone or in combination was used to search from PubMed and Embase by applying the filters of the title and the publication years between January 2000 and March 2020. Endometriosis is a chronic inflammatory disease characterized by repeated episodes of hemorrhage. Methemoglobin in repeated hemorrhage produces large amounts of superoxide anion via the autoxidation of hemoglobin. Excessive free-radical production causes redox imbalance, leading to inadequate antioxidant defenses and damage to endometrial cells, but may contribute to endometrial cell growth and survival through activation of various signaling pathways. In addition, to overcome excessive oxidative stress, estradiol participates in the induction of antioxidants such as superoxide dismutase in mitochondria. Several antioxidants that suppress free radicals may be effective in endometriosis-related pain. We searched for 23 compounds and natural substances that could reduce the pain caused by superoxide/reactive oxygen species in basic research and animal models. Next, we built a list of 16 drugs that were suggested to be effective against endometriosis other than hormone therapy in preclinical studies and clinical trials. Of the 23 and 16 drugs, 4 overlapping drugs could be potential candidates for clinically reducing endometriosis-related pain caused by superoxide anion/reactive oxygen species. These drugs include polyphenols (resveratrol and polydatin), dopamine agonists (cabergoline), and statins (simvastatin). However, no randomized controlled trials have evaluated the efficacy of these drugs. In conclusion, this review summarizes the following 2 points: superoxide anion generation by methemoglobin is enhanced in endometriosis, resulting in redox imbalance; and some compounds and natural substances that can suppress free radicals may be effective in endometriosis-related pain. Further randomized clinical trials based on larger series are mandatory to confirm the promising role of antioxidants in the nonhormonal management of endometriosis.

Revisiting estrogen-dependent signaling pathways in endometriosis: Potential targets for non-hormonal therapeutics.

Endometriosis is an estrogen-dependent gynecologic disease. Endometriotic cells survive in oxidative stress and hypoxic environments. The aim of this review is to reconsider new therapeutic strategies for endometriosis by focusing on estrogen signaling, ROS production and scavenging, and mitochondrial metabolism. Each keyword alone or in combination was used to search from PubMed and Embase by applying the filters of the title and the publication years between January 2000 and May 2020. Abnormal epigenetic marks of estrogen receptors (ERs) in endometriosis cause overexpression of ERß, progesterone resistance, inflammation, anti-apoptosis, and mitochondrial metabolic modification. In addition to hormonal action, estrogen is involved in various functions such as mitochondrial biosynthesis and energy metabolism. Estrogen works with its downstream target genes to modulate mitochondrial gene expression, regulate ROS production, and affect mitochondrial biology, including ATP production, antioxidant defenses, mitochondrial biosynthesis, quality control, and energy-transducing capacity. Endometriosis can shift mitochondrial metabolism from oxidative phosphorylation to aerobic glycolysis. This metabolic conversion suppresses ROS production and thus activates the survival signal of endometriotic cells. Therefore, molecules associated with aerobic glycolysis and mitochondrial metabolism are considered therapeutic targets for endometriosis. In conclusion, estrogen downstream target genes involved in mitochondrial metabolic biosynthesis may be potential targets for non-hormonal treatment of endometriosis.

Anti-senescent drug screening by deep learning-based morphology senescence scoring.

Advances in deep learning technology have enabled complex task solutions. The accuracy of image classification tasks has improved owing to the establishment of convolutional neural networks (CNN). Cellular senescence is a hallmark of ageing and is important for the pathogenesis of ageing-related diseases. Furthermore, it is a potential therapeutic target. Specific molecular markers are used to identify senescent cells. Moreover senescent cells show unique morphology, which can be identified. We develop a successful morphology-based CNN system to identify senescent cells and a quantitative scoring system to evaluate the state of endothelial cells by senescence probability output from pre-trained CNN optimised for the classification of cellular senescence, Deep Learning-Based Senescence Scoring System by Morphology (Deep-SeSMo). Deep-SeSMo correctly evaluates the effects of well-known anti-senescent reagents. We screen for drugs that control cellular senescence using a kinase inhibitor library by Deep-SeSMo-based drug screening and identify four anti-senescent drugs. RNA sequence analysis reveals that these compounds commonly suppress senescent phenotypes through inhibition of the inflammatory response pathway. Thus, morphology-based CNN system can be a powerful tool for anti-senescent drug screening.

Independent and cumulative association of clinical and morphological heart failure with long-term outcome after percutaneous coronary intervention.

BACKGROUND: Heart failure (HF) is a risk factor for adverse post-procedural outcome after revascularization; however, it is unclear how left ventricular systolic dysfunction (LVSD) and clinical HF symptoms affect percutaneous coronary intervention (PCI) outcomes. We investigated the characteristics and long-term outcomes of patients with clinical HF or LVSD after PCI. METHODS: This was a Japanese multicenter registry study of adult patients receiving PCI. Among 4689 consecutive patients who underwent PCI at 15 hospitals from January 2009 to December 2012, we analyzed 2634 (56.2%) with documented left ventricular ejection fraction (LVEF). They were divided into four groups based on clinical HF (symptoms or HF hospitalization) and LVEF [≥35% and <35% (HF due to LVSD)]. The primary outcome was major adverse cardiovascular events (MACE), comprising all-cause death, acute coronary syndrome, HF hospitalization, performance of coronary artery bypass grafting, and stroke within 2 years after the initial PCI. RESULTS: Our findings revealed 354 patients (13.4%) with HF (clinical HF, n = 173, 48.9%; LVSD, n = 132, 37.3%; both, n = 49; 13.8%). The incidence of MACE was higher in patients with clinical HF or LVSD, and was largely due to higher non-cardiac death and HF hospitalization. After adjustment, clinical HF (hazard ratio 2.16, 95% confidence interval; 1.49-3.14) and lower LVEF (per 10%, hazard ratio 0.89, 95% confidence interval; 0.81-0.99) were independently associated with higher MACE risk. CONCLUSIONS: Clinical HF and LVSD were independently associated with adverse long-term clinical outcomes, particularly with non-cardiac death and HF readmission, in patients treated with PCI.

Clinical Significance of Guanylate Cyclase Stimulator, Riociguat, on Right Ventricular Functional Improvement in Patients with Pulmonary Hypertension.

BACKGROUND: Riociguat is a soluble guanylate cyclase stimulator that improves hemodynamics in patients with pulmonary hypertension (PH). Accumulating evidence implicates the additional effect of riociguat on the increase in cardiac output. However, its mechanisms have not been fully understood. This study aimed to investigate whether riociguat could ameliorate right ventricular (RV) contraction as well as hemodynamics. METHODS: We studied 45 patients with pulmonary arterial hypertension (14) or chronic thromboembolic pulmonary hypertension (31) and evaluated hemodynamics, using right-sided heart catheterization, before and after the administration of riociguat. RV function was assessed by echocardiography, including speckle-tracking echocardiography. RESULTS: Riociguat significantly improved the WHO functional class and reduced the mean pulmonary arterial pressure and vascular resistance. In addition, the cardiac index increased. RV remodeling was ameliorated after riociguat administration as assessed by the echocardiographic parameters, such as RV diameter and RV area index. RV function, including RV fractional area change and RV global longitudinal strain, also significantly improved, and their improvement was even observed in patients with mild PH after pulmonary endarterectomy or balloon pulmonary angioplasty. Furthermore, covariance analysis revealed that RV global longitudinal strain and RV fractional area change improved after riociguat administration, even with the same mean pulmonary arterial pressure, implicating the improvement of RV contractile function by riociguat, regardless of RV loading. CONCLUSIONS: Riociguat not only improved the hemodynamics of patients with PH but also ameliorated the echocardiographic parameters with RV function. RV strain could detect the subtle improvement in mild PH, and riociguat may have a benefit even after intervention, as assessed by speckle-tracking echocardiography.

Appropriate device selection for transcatheter atrial septal defect closure using three-dimensional transesophageal echocardiography.

Detail morphological evaluation for ASD is essential to achieve successful transcatheter closure. Three-dimensional transesophageal echocardiography (3D-TEE) is emerging, but few studies have comprehensively verified the usefulness of 3D-TEE. We divided 329 patients who underwent transcatheter ASD closure at our university hospital into 157 in the Conventional group evaluated with 2-dimensional transesophageal echocardiography and balloon sizing (BS), and 172 in the 3D-TEE group evaluated with 3D-TEE additionally. We assessed usefulness of 3D-TEE and consider appropriate device selection procedure. Overall, the percentage with re-sizing of device tended to be lower in the 3D-TEE group than in the Conventional group (10.1% vs 6.0%, p = 0.187). Among preprocedural modalities, the device size was mainly decided based on the BS diameter. A logistic regression analysis demonstrated that large atrial septum aneurysms (ASA) were associated with a ≥ 2 mm discrepancy of the BS diameter from the preprocedural 3D-TEE diameter (p < 0.05). Compared to the Amplatzer Septal Occluder, the differences in device size and the preprocedural ASD measurement were greater when using the Occlutech Figulla Flex II Occluder (FFII). Particularly, among the patients implanted with FFIIs, the discrepancies of the device size from the 3D-TEE measurement were greater in patients with large ASA than those with small ASA. Preprocedural 3D-TEE is useful to select the appropriate device size. Particularly, it is necessary to select a much larger device than that derived from the preprocedural 3D-TEE measurement when using FFII in patients with a septal aneurysm.

Regional Right Ventricular Abnormalities Implicate Distinct Pathophysiological Conditions in Patients With Chronic Thromboembolic Pulmonary Hypertension.

Background Right ventricular (RV) dysfunction is a prognostic factor for cardiovascular disease. However, its mechanism and pathophysiology remain unknown. We investigated RV function using RV-specific 3-dimensional (3D)-speckle-tracking echocardiography (STE) in patients with chronic thromboembolic pulmonary hypertension. We also assessed regional wall motion abnormalities in the RV and chronological changes during balloon pulmonary angioplasty (BPA). Methods and Results Twenty-nine patients with chronic thromboembolic pulmonary hypertension who underwent BPA were enrolled and underwent right heart catheterization and echocardiography before, immediately after, and 6 months after BPA. Echocardiographic assessment of RV function included both 2-dimensional-STE and RV-specific 3D-STE. Before BPA, global area change ratio measured by 3D-STE was significantly associated with invasively measured mean pulmonary artery pressure and pulmonary vascular resistance (r=0.671 and r=0.700, respectively). Dividing the RV into the inlet, apex, and outlet, inlet area change ratio showed strong correlation with mean pulmonary artery pressure and pulmonary vascular resistance before BPA (r=0.573 and r=0.666, respectively). Only outlet area change ratio was significantly correlated with troponin T values at 6 months after BPA (r=0.470), and its improvement after BPA was delayed compared with the inlet and apex regions. Patients with poor outlet area change ratio were associated with a delay in RV reverse remodeling after treatment. Conclusions RV-specific 3D-STE analysis revealed that 3D RV parameters were novel useful indicators for assessing RV function and hemodynamics in pulmonary hypertension and that each regional RV portion presents a unique response to hemodynamic changes during treatment, implicating that evaluation of RV regional functions might lead to a new guide for treatment strategies.

Relationship between adenomyosis and endometriosis; Different phenotypes of a single disease?

Adenomyosis and endometriosis are common gynecological disorders, but their pathophysiology is still under debate. The aim of this review is to discuss whether adenomyosis and endometriosis represent two different entities or different phenotypes of a single disease. We searched PubMed electronic databases published between January 2000 and April 2020. Endometriosis is classified into three phenotypes; superficial peritoneal disease (SUP), ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) lesions. Adenomyosis presents several different subtypes, including intrinsic adenomyosis, extrinsic adenomyosis, adenomyosis externa and focal adenomyosis located in the outer myometrium (FAOM). Human uterus is embryologically composed of archimetra, originating from the Müllerian duct, and neometra, arising from the non-Müllerian duct, and adenomyosis and endometriosis are diseases of archimetra. The outer myometrial layer of the uterus is composed of highly differentiated smooth muscle cells (SMCs), while the inner myometrial cells are immature. Inappropriate uterine contractions can cause retrograde menstruation and chronic inflammation in the pelvic cavity, then influencing the development of pelvic endometriosis. Furthermore, hyperperistalsis results in physiological and pathological changes to the endometrial-myometrial junctional barrier, allowing invagination of the normal endometrial tissue into the inner myometrial layer. This can trigger the development of intrinsic adenomyosis. There are insufficient data available to draw conclusions, but extrinsic adenomyosis may result from pelvic endometriosis and FAOM from rectal and bladder DIE/adenomyosis externa. In conclusions, this paper contributes to the debate in the possibility that adenomyosis and endometriosis represent different phenotypes of a single disease.