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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.

BackgroundLung 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.MethodsThis 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.ResultsThe 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

BackgroundWith 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.MethodsWe 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.ResultsIn 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.ConclusionReduced 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.

BackgroundChronic 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.MethodsThis 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.ResultsThe 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.ConclusionseGFR (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.

We investigated the relationship between basketball free-throw accuracy and anthropometry, physical fitness tests, and performance variables among 16 collegiate female basketball players. Each participant performed 20 basketball free throws. Anthropometric measures were height and weight; physical fitness tests were sit-and-reach, back strength, and grip strengths; other basketball performance variables were the phases of the pre-shoot routine: (a) time taken, (b) minimum angle when taking the ball back, (c) angle at ball release, (d) angular displacement during the forward arm swing, and (e) angular velocity at ball release on the elbow, shoulder, hip, knee, and ankle. We analyzed the correlation between free-throw accuracy and data on anthropometry and physical fitness, the time period and variability of the pre-shot routine, and kinematic data. There were negative correlations between free-throw accuracy and mean pre-shot time, and variability of the pre-shot time, indicating that participants with a shorter and less variable pre-shot time showed a higher free-throw accuracy. Angular displacement of the shoulder during the forward swing and angular velocity of the knee at ball release showed positive correlations with free-throw accuracy. There was also a negative correlation between free-throw accuracy and variability of angular displacement during the forward swing at the elbow, indicating that participants with smaller variability of angular displacement of the elbow showed higher free-throw accuracy. Some performance variables, including routine duration, angular displacement of the shoulder and elbow, and angular velocity of the knee, were related to free-throw accuracy.

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.

We examined the mechanisms for effects of luteolin on transcriptional regulation of the Niemann-Pick C1-Like 1 (NPC1L1) gene. Exposure of Caco-2 cells to luteolin for 48 h significantly attenuated the levels of NPC1L1 mRNA and protein. In phenomenon as well, cholesterol uptake to Caco-2 cells was decreased while they were exposed to lueolin for 48 h. Sterol-regulatory element-binding protein 2 (SREBP2) activated NPC1L1 transcription. Hepatocyte nuclear factor 4α (HNF4α) stimulated the transcription of NPC1L1 along with SREBP2. Reporter gene assays were performed using human NPC1L1 promoter and co-transfected SREBP2 and HNF4α constructs, with the result that the luciferase activity of NPC1L1 promoter was induced by co-transfection of SREBP2, and luteolin reduced this activity. Luteolin also decreased the SREBP2 and HNF4α expression. In conclusion, luteolin inhibited the expression of NPC1L1 by decreasing the expression of SREBP2 and HNF4α and by inhibiting SREBP2 access to the binding elements in the promoter region.

Niemann-Pick C1-Like 1 (NPC1L1) mediates cholesterol absorption, and ezetimibe is a potent NPC1L1 inhibitor applicable for medication of hypercholesterolemia. Epidemiological studies demonstrated that consumption of polyphenols correlates with a decreased risk for atherosclerosis due to their antioxidant effect. This activity can hardly be attributable to the antioxidant activity only, and we hypothesized that polyphenols inhibit intestinal transport of cholesterol. We elucidated the kinetic parameters of intestinal cholesterol absorption, screened several polyphenols for their ability to specifically inhibit intestinal cholesterol absorption, and determined the inhibitory effects of selected flavonoids in vitro and in vivo. The concentration-dependent uptake of cholesterol by Caco-2 cells obeyed a monophasic saturation process. This indicates the involvement of an active-passive transport, i.e., NPC1L1. Parameters of cholesterol uptake by Caco-2 cells were as follows: Jmax, Kt, and Kd were 6.89±2.96 19.03±11.58 µM, and 0.11±0.02 pmol/min/mg protein, respectively. Luteolin and quercetin inhibited cholesterol absorption by Caco-2 cells and human embryonic kidney 293T cells expressing NPC1L1. When preincubated Caco-2 cells with luteolin and quercetin before the assay, cholesterol uptake significantly decreased. The inhibitory effects of these flavonoids were maintained for up to 120 min. The level of inhibition and irreversible effects were similar to that of ezetimibe. Serum cholesterol levels significantly decreased more in rats fed both cholesterol and luteolin (or quercetin), than in those observed in the cholesterol feeding group. As quercetin induced a significant decrease in the levels of NPC1L1 mRNA in Caco-2 cells, the in vivo inhibitory effect may be due to the expression of NPC1L1. These results suggest that luteolin and quercetin reduce high blood cholesterol levels by specifically inhibiting intestinal cholesterol absorption mediated by NPC1L1.