Indexed aortic valve area using multimodality imaging for assessing the severity of bicuspid aortic stenosis.

BACKGROUND: The impact of various imaging modalities on discordance/concordance between indexed aortic valve area (iAVA) and catheterization-derived mean transaortic pressure gradient (mPGcath) is unclear in patients with bicuspid aortic valve (BAV). This study aimed to compare iAVA measurements obtained using four different methodologies in BAV and tricuspid aortic valve (TAV) patients, using mPGcath as a reference standard. METHODS: We retrospectively reviewed patients who underwent comprehensive assessment of AS, including two-dimensional (2D) transthoracic echocardiography (TTE), three-dimensional (3D) transesophageal echocardiography (TEE), multidetector computed tomography (MDCT), and catheterization, at our institution between 2019 and 2022. iAVA was measured using the continuity eq. (CE) with left ventricular outflow tract area obtained by 2D TTE, 3D TEE, and MDCT, as well as planimetric 3D TEE. RESULTS AND CONCLUSIONS: Among 564 patients (64 with BAV and 500 with TAV), 64 propensity-matched pairs of patients with BAV and TAV were analyzed. iAVACE(2DTTE) led to overestimation of AS severity (BAV, 23.4%; TAV, 28.1%) and iAVACE(MDCT) led to underestimation of AS severity (BAV, 29.3%; TAV, 16.7%), whereas iAVACE(3DTEE) and iAVAPlani(3DTEE) resulted in a reduction in the discordance of AS grading. A moderate correlation was observed between mPGcath and iAVACE(3DTEE) (BAV, r = -0.63; TAV, r = -0.68), with iAVACE(3DTEE) corresponding to the current guidelines' cutoff value (BAV, 0.58 cm2/m2; TAV, 0.60 cm2/m2). Discordance/concordance between iAVA and mPGcath in evaluating AS severity varies depending on the methodology and imaging modality used. The use of iAVACE(3DTEE) is valuable for reconciling the discordant AS grading in BAV patients as well as TAV.

Prognostic Implication of Right Ventricular Free Wall Longitudinal Strain and Right Atrial Pressure Estimated By Echocardiography in Patients With Severe Functional Tricuspid Regurgitation.

BACKGROUND: The interaction between right ventricular (RV) function and pulmonary hypertension is crucial for prognosis of patients with severe functional tricuspid regurgitation. RV free wall longitudinal strain (RVFWLS) has been reported to detect RV systolic dysfunction earlier than other conventional parameters. Although pulmonary artery systolic pressure measured by Doppler echocardiography is often underestimated in severe functional tricuspid regurgitation, right atrial pressure (RAP) estimated by echocardiography may be viewed as a prognostic factor. Impact of RAP and RVFWLS on outcome in patients with severe functional tricuspid regurgitation remains unclear. The aim of the present study was to investigate prognostic implication of RAP, RVFWLS, and their combination in this population. METHODS AND RESULTS: We retrospectively examined 377 patients with severe functional tricuspid regurgitation. RAP, pulmonary artery systolic pressure, RV fractional area change, and RVFWLS were analyzed. RAP of 15 mm Hg was classified as elevated RAP. All-cause death at 2-year follow-up was defined as the primary end point. RVFWLS provided better prognostic information than RV fractional area change by receiver operating characteristic curve analysis. In the multivariable Cox regression analysis, elevated RAP and RVFWLS of ≤18% were independent predictors of clinical outcome. Patients with RVFWLS of ≤18% had higher risk of all-cause death than those without by Kaplan-Meier curve analysis. Furthermore, when patients were stratified into 4 groups by RAP and RVFWLS, the group with elevated RAP and RVFWLS of ≤18% had the worst outcome. CONCLUSIONS: Elevated RAP and RVFWLS of ≤18% were independent predictors of all-cause death. The combination of elevated RAP and RVFWLS effectively stratified the all-cause death.

Impact of stroke volume assessment by three-dimensional transesophageal echocardiography on the classification of low-gradient aortic stenosis.

BACKGROUND: Accurate assessment of flow status is crucial in low-gradient aortic stenosis (AS). However, the clinical implication of three-dimensional transesophageal echocardiography (3DTEE) on flow status evaluation remains unclear. This study aimed to investigate the assessment of flow status using 3D TEE in low-gradient AS patients. METHODS: We retrospectively reviewed patients diagnosed with low-gradient AS and preserved ejection fraction at our institution between 2019 and 2022. Patients were categorized into low-flow/low-gradient (LF-LG) AS or normal-flow/low-gradient (NF-LG) AS based on two-dimensional transthoracic echocardiography (2DTTE). We compared the left ventricular outflow tract (LVOT) geometry between the two groups and reclassified them using stroke volume index (SVi) obtained by 3DTEE. RESULTS: Among 173 patients (105 with LF-LG AS and 68 with NF-LG AS), 54 propensity-matched pairs of patients were analyzed. 3DTEE-derived ellipticity index of LVOT was significantly higher in LF-LG AS patients compared to NF-LG AS patients (p = 0.012). We assessed the discordance in flow status classification between SVi2DTTE and SVi3DTEE in both groups using a cutoff value of 35 ml/m2. The LF-LG AS group exhibited a significantly higher discordance rate compared to the NF-LG AS group, with rates of 50% and 2%, respectively. The optimal cutoff values of SVi3DTEE for identifying low flow status, based on 2DTTE-derived cutoff values, were determined to be 43 ml/m2. CONCLUSIONS: LVOT ellipticity in low-gradient AS patients varies depending on flow status, and this difference contributes to discrepancies between SVi3DTEE and SVi2DTTE, particularly in LF-LG AS patients. Utilizing SVi3DTEE is valuable for accurately assessing flow status.

One-pot gram-scale rapid synthesis of MN4 complexes with 14-membered ring macrocyclic ligand as a precursor for carbon-based ORR and CO2RR catalysts.

Herein, CoN4, CuN4, and NiN4 complexes with a 14-membered ring hexaazamacrocycle ligand H2HAM were synthesised as precursors for ORR and CO2RR catalysts via a one-pot, gram-scale synthesis procedure, which involved microwave heating for only 10 min. Detailed structures of the obtained 14MR-MN4 complex were revealed by single-crystal X-ray diffraction measurements.

Echocardiographic Characteristics of Left and Right Ventricular Longitudinal Function in Patients With a History of Cardiac Surgery.

Previous studies have indicated a reduction in right ventricular (RV) longitudinal motion after cardiac surgery. However, the long-term effect of cardiac surgery on longitudinal motion and the involvement of left ventricular (LV) motion remains unclear. Therefore, this study aimed to comprehensively investigate the longitudinal function of the right ventricle and left ventricle in patients who underwent cardiac surgery. The study included patients who underwent comprehensive transthoracic echocardiography with 3-dimensional RV data sets. By propensity score matching of the clinical and echocardiographic variables, including LV and RV ejection fraction, the echocardiographic parameters were compared between patients with and without a history of cardiac surgery (the surgery and nonsurgery groups, respectively). In this study, the surgery group had significantly lower LV global longitudinal strain values than the nonsurgery group, despite having similar LV ejection fraction. The tricuspid annular plane systolic excursion (TAPSE), tricuspid annular velocity, and RV free wall longitudinal strain were also significantly smaller in the surgery group, whereas the RV ejection fraction was comparable between the 2 groups. In addition, a subgroup analysis based on the time from previous surgery to transthoracic echocardiography (≤1 and >1 year) revealed that TAPSE was reduced in both postoperative phases. In conclusion, LV and RV longitudinal parameters were reduced after cardiac surgery, despite preserved LV and RV global functions. Moreover, TAPSE was reduced even after a long time after cardiac surgery. These findings emphasize the need for careful interpretation of biventricular longitudinal motion in patients with a history of cardiac surgery.

Comparison of prognostic value among echocardiographic surrogates of right ventricular-pulmonary arterial coupling: A three-dimensional echocardiographic study.

OBJECTIVES: Right ventricular (RV)-pulmonary arterial (PA) coupling is important in various cardiac diseases. Recently, several echocardiographic surrogates for RV-PA coupling have been proposed and reported to be useful in predicting outcomes. However, it remains unclear which surrogate is the most clinically relevant. This study aimed to comprehensively compare the prognostic value of different echocardiographic RV-PA coupling surrogates. METHODS: We retrospectively reviewed 242 patients with various cardiac conditions who underwent comprehensive transthoracic echocardiography with three-dimensional RV data. In addition to conventional parameters including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and PA systolic pressure (PASP), we analyzed RV free wall and global longitudinal strain (FWLS and GLS). We also obtained RV ejection fraction (RVEF), stroke volume (SV), and end-systolic volume (ESV) using three-dimensional RV analysis. RV-PA coupling surrogates were calculated as TAPSE/PASP, FAC/PASP, FWLS/PASP, GLS/PASP, RVEF/PASP, and SV/ESV. The study endpoint was a composite outcome of all-cause death or cardiovascular hospitalization within 1 year. RESULTS: In multivariable analysis, all the RV-PA coupling surrogates were independent predictors of the outcome. Among the surrogates, the model with TAPSE/PASP showed the lowest prognostic value in model fit and discrimination ability, whereas the model with RVEF/PASP exhibited the highest prognostic value. The partial likelihood ratio test indicated that the model with RVEF/PASP was significantly better than the model with TAPSE/PASP (p < .024). CONCLUSION: All the RV-PA coupling surrogates were independent predictors of the outcome. Notably, RVEF/PASP had the highest prognostic value among the surrogates.

Long-Term Impact of Small Mitral Valve Orifice Area after Transcatheter Edge-to-Edge Mitral Valve Repair on Clinical Outcome: A Three-Dimensional Echocardiography Study.

BACKGROUND: Iatrogenic mitral stenosis is a complication associated with transcatheter edge-to-edge mitral valve repair. Some reports revealed the impact of mean transmitral pressure gradient after procedure on long-term clinical outcomes. However, the association between prognosis and mitral valve orifice area (MVA) after the procedure has been poorly studied. This study aimed to investigate the association between postprocedural small MVA, derived from three-dimensional (3D) transesophageal echocardiography (TEE), and long-term clinical outcomes in 2 cohorts: the degenerative mitral regurgitation (MR) cohort and the functional MR cohort. METHODS: This retrospective study assessed 279 consecutive patients with 3D TEE data during transcatheter edge-to-edge mitral valve repair between January 2010 and December 2016. Mitral valve orifice area after device implantation was measured by 3D planimetry. The patients with degenerative and functional MR were stratified separately into 2 groups according to postprocedural MVA: normal MVA (MVA > 1.5 cm2) group and small MVA (MVA ≤ 1.5 cm2) group. RESULTS: Of the 279 patients, 142 (51%) had degenerative MR and 137 (49%) had functional MR. The number of degenerative MR patients with small MVA was 38, whereas 42 patients were in the functional MR cohort. Patients with small MVA had higher rate of all-cause mortality in the degenerative MR group (log-rank test: P = .01) but not in the functional MR group (log-rank test: P = .52). In multivariate analysis small MVA was independently associated with all-cause mortality but not postprocedural transmitral pressure gradient. Neither small MVA nor transmitral pressure gradient was associated with all-cause mortality in patients with functional MR. CONCLUSION: Small MVA measured by 3D TEE after transcatheter mitral edge-to-edge repair was associated with poor prognosis in patients with degenerative MR.

Quantification of pulmonary perfusion using LSIM-CT correlates with pulmonary hemodynamics in patients with CTEPD.

Background: Lung subtraction iodine mapping (LSIM)-CT is a clinically useful technique that can visualize pulmonary mal-perfusion in patients with chronic thromboembolic pulmonary disease (CTEPD). However, little is known about the associations of LSIM images with hemodynamic parameters of patients with CTEPD. This study investigates a parameter of LSIM images associated with mean pulmonary arterial pressure (mPAP) and validates the association between pulmonary vascular resistance, right atrial pressure, cardiac index, and exercise capacity in patients with CTEPD. Methods: This single-center, prospective, observational study involved 30 patients diagnosed with CTEPD using lung perfusion scintigraphy. To examine the correlation of decreased pulmonary perfusion area (DPA) with mPAP, areas with 0-10, 0-15, 0-20, and 0-30 HU in lung subtraction images were adopted in statistical analysis. The DPA to total lung volume ratio (DPA ratio, %) was calculated as the ratio of each DPA volume to the total lung volume. To assess the correlation between DPA ratios of 0-10, 0-15, 0-20, and 0-30 HU and mPAP, Spearman's rank correlation coefficient was used. Results: The DPA ratio of 0-10 HU had the most preferable correlation with mPAP than DPA ratios of 0-15, 0-20, and 0-30 HU (ρ = 0.440, P = 0.015). The DPA ratio of 0-10 HU significantly correlates with pulmonary vascular resistance (ρ = 0.445, P = 0.015). The receiver operating characteristic curve analysis indicated that the best cutoff value of the DPA ratio of 0-10 HU for the prediction of an mPAP of ≥30 mmHg was 8.5% (AUC, 0.773; 95% CI, 0.572-0.974; sensitivity, 83.3%; specificity, 75.0%). Multivariate linear regression analysis, which was adjusted for the main pulmonary arterial to ascending aortic diameter ratio and right ventricular to left ventricular diameter ratio, indicated that the DPA ratio of 0-10 HU was independently and significantly associated with mPAP (B = 89.7; 95% CI, 46.3-133.1, P < 0.001). Conclusion: The DPA ratio calculated using LSIM-CT is possibly useful for estimating the hemodynamic status in patients with CTEPD.

Effect of right ventricular free wall longitudinal strain on all-cause death in patients with isolated severe tricuspid regurgitation and atrial fibrillation.

Background: With the aging population and advanced catheter-based therapy, isolated tricuspid regurgitation (TR) with atrial fibrillation (AF) has gained increased attention; however, data on the prognostic effect of isolated TR with AF are limited because of the small number of patients among those with severe TR. Recently, right ventricular (RV) longitudinal strain by two-dimensional speckle-tracking echocardiography has been reported as an excellent indicator of RV dysfunction in severe TR. However, the prognostic implications of RV longitudinal strain in isolated severe TR associated with AF remain unclear. Therefore, this study aimed to reveal the prognostic value of this index in this population. Methods: We retrospectively studied patients with severe isolated TR associated with AF in the absence of other etiologies in the Cedars-Sinai Medical Center between April 2015 and March 2018. Baseline clinical and echocardiographic data were studied including RV systolic function evaluated by RV free wall longitudinal strain (FWLS) and conventional parameters. All-cause death was defined as the primary endpoint. Results: In total, 53 patients (median age, 85 years; female, 60%) with a median follow-up of 433 (60-1567) days were included. Fourteen patients (26%) died, and 66% had right heart failure (RHF) symptoms. By multivariable analysis, reduced RVFWLS was independently associated with all-cause death. Patients with RVFWLS of ≤18% had higher risk of all-cause death adjusted for age (log-rank P = 0.030, adjusted hazard ratio 4.00, 95% confidence interval, 1.11-14.4; P = 0.034). When patients were stratified into four groups by RHF symptoms and RVFWLS, the group with symptomatic and reduced RVFWLS had the worst outcome. Conclusion: Reduced RVFWLS was independently associated with all-cause death in patients with isolated severe TR and AF. Our subset classification showed the worst outcome from the combination of RHF symptoms and reduced RVFWLS.

Tricuspid annular area and leaflets stretch are associated with functional tricuspid regurgitation - insights from three-dimensional transesophageal echocardiography.

BACKGROUND: The presence of functional tricuspid regurgitation (TR) is associated with mortality and morbidity. Although uniform management with a tricuspid annuloplasty ring is currently considered as a standard surgical procedure, high rates of residual TR despite annuloplasty are reported. Therefore, the identification of the TR mechanisms would be necessary to provide personalized treatment for each TR patient. METHODS: This study population consisted of 106 patients with mitral regurgitation (MR) who were scheduled for procedure. Transthoracic and transesophageal echocardiography were performed prior to mitral valve intervention. We performed three-dimensional quantitative assessment including tricuspid annular (TA) area and the distance between the three commissures of tricuspid valve. RESULTS: Significant TR, which is defined as moderate or greater TR, was detected in 23 (22%). TA area (P < 0.01), the distance of septal-leaflet length (SL) (P = 0.03) and posterior-leaflet length (PL) (p = 0.02) were significantly associated with significant TR, while TA diameter assessed by transthoracic echocardiography was not. When patients were divided into four groups according to SL and PL, the group with longer SL and PL had a significantly higher incidence of significant TR (P < 0.01). CONCLUSIONS: Greater stretch of the septal and posterior leaflet between commissures and larger TA area are associated with significant TR in patients with severe MR. In order to prevent TR recurrence, the intervention of the septal leaflet in tricuspid annuloplasty may be beneficial. The precise implement of three-dimensional transesophageal echocardiography of tricuspid valve is valuable for a personalized strategy of tricuspid annuloplasty.

Impact of cystatin C-derived glomerular filtration rate in patients undergoing transcatheter aortic valve implantation.

Background: Chronic kidney disease (CKD) impacts prognosis in patients undergoing transcatheter aortic valve implantation (TAVI). While estimated glomerular filtration rate (eGFR) calculated from serum creatinine [eGFR (creatinine)] is affected by body muscle mass which reflects frailty, eGFR calculated from serum cystatin C [eGFR (cystatin C)] is independent of body composition, resulting in better renal function assessment. Methods: This study included 390 consecutive patients with symptomatic severe aortic stenosis (AS) who underwent TAVI, and measured cystatin C-based eGFR at discharge. Patients were divided into two groups, with or without CKD estimated with eGFR (cystatin C). The primary endpoint of this study was the 3-year all-cause mortality after TAVI. Results: The median patient age was 84 years, and 32.8% patients were men. Multivariate Cox regression analysis indicated that eGFR (cystatin C), diabetes mellitus, and liver disease were independently associated with 3-year all-cause mortality. In the receiver-operating characteristic (ROC) curve, the predictive value of eGFR (cystatin C) was significantly higher than that of eGFR (creatinine). Furthermore, Kaplan-Meier estimates revealed that 3-year all-cause mortality was higher in the CKD (cystatin C) group than that in the non-CKD (cystatin C) group with log-rank p = 0.009. In contrast, there was no significant difference between the CKD (creatinine) and non-CKD (creatinine) groups with log-rank p = 0.94. Conclusions: eGFR (cystatin C) was associated with 3-year all-cause mortality in patients who underwent TAVI, and it was superior to eGFR (creatinine) as a prognostic biomarker.

Vaso reactivity test using inhaled nitric oxide for pulmonary arterial hypertension accompanied by severe interstitial lung disease attributed to systemic sclerosis: A case report.

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. .

Left atrial volume index predicts future improvement of B-type natriuretic peptide levels after transcatheter aortic valve replacement.

In patients with symptomatic severe aortic stenosis (AS), those who experienced readmission due to heart failure after transcatheter aortic valve replacement (TAVR) showed poor prognosis. Furthermore, poor B-type natriuretic peptide (BNP) improvement is associated with increased morbidity and mortality. However, little is known about the clinical parameters related to the change in BNP levels after TAVR procedure. This study population consisted of 127 consecutive patients of symptomatic severe AS with preserved ejection fraction (EF) who underwent transfemoral TAVR (TF-TAVR). Comprehensive transthoracic echocardiography was performed prior to the day of TF-TAVR. BNP was measured serially before and 1 year after TF-TAVR. The median BNP level was significantly decreased from 252.5 pg/ml to 146.8 pg/ml in all 127 patients 1 year after TF-TAVR (P < 0.01). However, the patients could be divided into 2 groups according to decrease (72%) or increase (28%) in plasma BNP level. Multivariate logistic regression analysis revealed that Aortic valve (AV) peak velocity, pre-procedural BNP, and larger left atrial volume index (LAVI) were found to be an independent predictor of increased BNP level 1 year after TAVR (OR 0.55, 95% CI 0.38-0.77; P < 0.01). LAVI were negatively correlated with the change in BNP level before and 1 year after TAVR (r = 0.47, P < 0.01). The ROC analysis demonstrated that 52.9 ml/m2 was the optimal cut-off value of LAVI for decreasing BNP 1 year after TAVR (area under the curve 0.69) with 64% sensitivity and 70% specificity. In addition to AV peak velocity and pre-procedural BNP, LAVI independently predicts future improvement of BNP levels 1 year after TAVR. Our findings indicate an additive predictive value of assessment of LAVI before TAVR procedure for risk stratification.

Kihon checklist is useful for predicting outcomes in patients undergoing transcatheter aortic valve implantation.

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. METHODS: This single-center prospective observational study included 280 consecutive patients with symptomatic severe aortic stenosis who underwent TAVI and evaluated pre-procedural physical performance focused on frailty at our institution. We assessed all patients' frailty by the KCL before TAVI, as described previously. We set the primary endpoint as the 3-year all-cause mortality after TAVI. RESULTS: The median patient age was 84 years (interquartile range, 81-87 years), and 31.1% were men. In the receiver operating characteristics curve, there were no significant differences between the KCL and Cardiovascular Health Study frailty index [area under the curve (AUC) 0.625 versus 0.628; p=0.93), KCL and Rockwood Clinical Frailty Scale (AUC 0.625 versus 0.542; p=0.15), and KCL and Short Physical Performance Battery (AUC 0.625 versus 0.612; p=0.91). The first and second tertiles of the total KCL score were 8 and 12, respectively. The multivariate Cox regression model indicated that the total KCL score [hazard ratio (HR), 1.104; 95% confidence interval (CI), 1.034-1.179; p=0.003], presence of diabetes mellitus (HR, 1.993; CI, 1.055-3.766; p=0.03), and presence of liver disease (HR, 3.007; CI, 1.067-8.477; p=0.04) were independently associated with 3-year all-cause mortality. CONCLUSIONS: The KCL is a simple and useful tool for evaluating frailty status and predicting 3-year all-cause mortality in patients undergoing TAVI.

Modulatory Effect of Theaflavins on Apical Sodium-Dependent Bile Acid Transporter (ASBT) Activity.

Inhibiting apical sodium-dependent bile acid transporter (ASBT) has been identified as a potential strategy to reduce plasma cholesterol levels. Thus, in this study, we aimed to identify polyphenols that inhibited ASBT activity and to elucidate their mechanism. ASBT is responsible for most of the taurocholic acid (TC) uptake in Caco-2 cells. Of the 39 polyphenols examined, theaflavin (TF)-3-gallate (TF2A) and theaflavin-3'-gallate (TF2B) have been found to significantly reduce TC uptake in Caco-2 cells to 37.4 ± 2.8 and 33.8 ± 4.0%, respectively, of that in the untreated cells. The results from the TC uptake assay using N-acetylcysteine suggested that the inhibitory effect of TF2A and TF2B was attributed to the oxidization of their benzotropolone rings and their covalent bonding with ASBT's cysteine. TC uptake was reduced in the COS-7 cells expressing recombinant ASBT whose cysteine residues were mutated to alanine. Finally, the substrate concentration-dependent TC uptake assay showed that TFs competitively inhibited TC uptake.

Novel assays to monitor gene expression and protein-protein interactions in rice using the bioluminescent protein, NanoLuc.

Luciferases have been widely utilized as sensitive reporters to monitor gene expression and protein-protein interactions. Compared to firefly luciferase (Fluc), a recently developed luciferase, Nanoluciferase (NanoLuc or Nluc), has several superior properties such as a smaller size and stronger luminescence activity. We compared the reporter properties of Nluc and Fluc in rice (Oryza sativa). In both plant-based two-hybrid and split luc complementation (SLC) assays, Nluc activity was detected with higher sensitivity and specificity than that with Fluc. To apply Nluc to research involving the photoperiodic regulation of flowering, we made a knock-in rice plant in which the Nluc coding region was inserted in-frame with the OsMADS15 gene, a target of the rice florigen Hd3a. Strong Nluc activity in response to Hd3a, and in response to change in day length, was detected in rice protoplasts and in a single shoot apical meristem, respectively. Our results indicate that Nluc assay systems will be powerful tools to monitor gene expression and protein-protein interaction in plant research.

Academic Research Consortium High Bleeding Risk Criteria associated with 2-year bleeding events and mortality after transcatheter aortic valve replacement discharge: a Japanese Multicentre Prospective OCEAN-TAVI Registry Study.

Aims: To investigate the ability of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria and ARC-HBR score to predict 2-year bleeding and mortality in patients undergoing transcatheter aortic valve replacement (TAVR). Methods and results: We enrolled 2514 patients who underwent successful TAVR during 2013-17. In this study, we used the ARC-HBR score for further HBR-risk stratification, and the ARC-HBR score was calculated as follows: each major criterion was 2 points and each minor criterion was 1 point. The impact of the ARC-HBR criteria and increasing ARC-HBR score on the incidence of moderate/severe bleeding events, mortality, and ischaemic stroke in the first 2 years were evaluated. We used survival classification and regression tree (CART) analysis for 2-year moderate or severe bleeding events, and patients were statistically classified into HBR low- (ARC-HBR score ≤1), intermediate- (ARC-HBR score = 2-4), or high-risk (ARC-HBR score ≥5) groups, and 91.4% were at HBR (ARC-HBR score ≥2). The rates of 2-year moderate/severe bleeding events and all-cause mortality were higher in the ARC-HBR group and highest in the HBR high-risk group. An increased HBR score was significantly associated with moderate/severe bleeding events [hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.07-1.31; P = 0.001] and all-cause mortality (adjusted HR 1.24, 95% CI 1.17-1.32; P < 0.001). Conclusions: The ARC-HBR criteria identify patients at HBR after TAVR; an increased ARC-HBR score is associated with 2-year moderate/severe bleeding events and mortality.

Presence of mitral stenosis is a risk factor of new development of acute decompensated heart failure early after transcatheter aortic valve implantation.

AIMS: Acute decompensated heart failure (ADHF) can occur early after transcatheter aortic valve implantation (TAVI), but the risk factors or mechanisms associated with it have not been fully determined. This hypothesis-generating study aimed to investigate the clinical indices associated with the development of ADHF within 72 hours after TAVI and to improve procedural approaches for TAVI. METHOD AND RESULTS: In this single-centre hypothesis generating prospective observational study, we enrolled 156 consecutive patients with severe aortic stenosis who underwent TAVI between January 2016 and February 2018 at our institution. We set the primary endpoint as the new development of ADHF within 72 hours after TAVI, and clinical indices associated with it were evaluated using a multivariable logistic model. The median age of the patients was 83 (quartile range 80-86) years, 48 (30.8%) were men and the median Society of Thoracic Surgery-Predicted Risk of Mortality was 7.1 (range 5.2-10.4). Mitral stenosis (MS), defined as mean transmitral valve pressure gradient ≥5 mm Hg, was present in 15 (9.6%) patients. After TAVI, the invasive mean transaortic valve pressure gradient (mAVPG) decreased from 48 (36-66) to 7 (5-11) mm Hg, and 12 (7.7%) patients developed ADHF within 72 hours after TAVI. Multivariable logistic regression analysis showed that MS (adjusted OR, 14.227; 95% CI 2.654 to 86.698; p=0.002) and greater decreases in mAVPG (1.038; 1.003 to 1.080; p=0.044) were associated with ADHF. CONCLUSIONS: MS and drastic improvement of mAVPG were associated with new development of ADHF within 72 hours after TAVI.

Short-term mastication after weaning upregulates GABAergic signalling and reduces dendritic spine in thalamus.

Mastication enhances brain function and mental health, but little is known about the molecular mechanisms underlying the effects of mastication on neural development in early childhood. Therefore, we analysed the gene expression in juvenile neural circuits in rats fed with a soft or chow diet immediately after weaning. We observed that the gene expression patterns in the thalamus varied depending on the diet. Furthermore, gene ontology analysis revealed that two terms were significantly enhanced: chemical synaptic transmission and positive regulation of dendritic spine morphogenesis. With respect to chemical synaptic transmission, glutamate decarboxylase and GABA receptors were upregulated in the chow diet group. The related genes, including vesicular GABA transporter, were also upregulated, suggesting that mastication activates GABAergic signalling. With respect to dendritic spine morphogenesis, Ingenuity Pathway Analysis predicted fewer extension of neurites and neurons and fewer number of branches in the chow diet group. The numbers of spines in the ventral posterolateral and posteromedial regions were significantly decreased. These results suggest that mastication in the early developing period upregulates GABAergic signalling genes, with a decrease of spines in the thalamus.