Non-classical 11ß-hydroxylase deficiency caused by a novel heterozygous mutation: a case report and review of the literature.

PURPOSE: 11ß-hydroxylase deficiency (11ß-OHD) constitutes a rare form of congenital adrenal hyperplasia (CAH), typically accounting for ~5-8% of CAH cases. Non-classical 11ß-OHD is reported even more rarely and frequently results in misdiagnosis or underdiagnosis due to its mild clinical symptoms. METHODS: A clinical, biochemical, radiological, and genetic study was conducted on a 9-year-old girl presenting with mild breast development, axillary hair growth, and advanced bone age. Additionally, a comprehensive review and synthesis of the literature concerning 11ß-OHD were conducted. RESULTS: The patient presented with breast enlargement, axillary hair development, and accelerated growth over the past year. Laboratory tests revealed levels of cortisol, luteinizing hormone, testosterone, and progesterone that were below normal. A gonadotropin-releasing hormone (GnRH) stimulation test suggested the possibility of central precocious puberty. Radiologic examination revealed a 2-year advance in bone age, while bilateral adrenal ultrasonography showed no abnormalities. Her mother exhibited hirsutism, while her father's physical examination revealed no abnormalities. Whole-exon genetic testing of the child and her parents indicated a heterozygous mutation of c.905_907delinsTT in exon 5 of the 11ß-hydroxylase gene (CYP11B1) in the child and her mother. This mutation resulted in a substitution of aspartic acid with valine at amino acid position 302 of the coding protein. This frameshift resulted in a sequence of 23 amino acids, culminating in a premature stop codon (p.Asp302ValfsTer23). A review of the previous literature revealed that the majority of heterozygous mutations in 11ß-OHD were missense mutations, occurring primarily in exons 2, 6, 7, and 8. The most common mutation among 11ß-OHD patients was the change of Arg-448 to His (R448H) in CYP11B1. Furthermore, bioinformatics analyses revealed that heterozygous mutation of c.905_907delinsTT had deleterious effects on the function of CYP11B1 and affected the stability of the protein, presumably leading to a partial impairment of enzyme activity. The results of the in vitro functional study demonstrated that the missense mutant (p.Asp302ValfsTer23) exhibited partial enzymatic activity. CONCLUSIONS: We report a novel heterozygous mutation of CYP11B1 (c.905_907delinsTT), enriching the spectrum of genetic variants of CYP11B1. This finding provides a valuable case reference for early diagnosis of non-classical patients with 11ß-OHD.

Step-by-step transesophageal echocardiographic guidance for transjugular transcatheter tricuspid valve replacement with a radial force-independent bioprosthesis.

The prohibitive risk of isolated tricuspid valve (TV) surgery encouraged rapid development of a transcatheter solution for tricuspid regurgitation (TR). The favorable results of these devices informed recent guidelines to recommend considering transcatheter treatment of symptomatic secondary severe TR in inoperable patients. Transcatheter TV repair systems usually reduce TR through leaflet approximation and direct annuloplasty. Orthotopic transcatheter TV replacement (TTVR) devices generally rely on radial force and tricuspid leaflet engagement for implantation and stability. The LuX-Valve is a novel radial force-independent orthotopic TTVR device that is operated through the trans-atrial approach. Its radial force-independency is achieved through an interventricular septal anchor tab (septal insertion) and two leaflet graspers (leaflet engagement). Such a unique design makes the intraprocedural imaging different from that of other currently available TTVR systems. The latest generation of this device, the LuX-Valve Plus, comes with a newly designed delivery system through the transjugular approach, which makes the intraprocedural monitoring and adjustment of the device even more complex for successful implantation. However, its unique imaging needs for intra-procedural guidance and post-operative evaluation have not been described before. Therefore, we aimed to elaborate the key steps of transesophageal echocardiography (TEE) to guide this novel procedure. Herein, the primary 2-dimensional (2D) and 3-dimensional (3D) echocardiographic work planes are proposed and the critical steps are emphasized for better communication between imagers and interventionists. The suitability of 2D and 3D echocardiography to guide this procedure is also discussed to increase the flexibility of choice during the implantation.

In vitro and clinical validation of different correction algorithms for the two-dimensional proximal isovelocity surface area method in a low-velocity flow field for quantifying tricuspid regurgitation.

Background: The 2-dimensional proximal isovelocity surface area (2D PISA) method underestimates tricuspid regurgitation (TR) severity. Previously proposed correction algorithms should be further scrutinized. Methods: Two correction algorithms were tested. One approach involves dividing the 2D PISA effective regurgitant orifice area by a constant of 0.7 (EROA0.7). Another approach involves multiplying the unadjusted EROA by Vorifice/(Vorifice - Valiasing), where Vorifice denotes the TR jet velocity, and Valiasing represents the color aliasing velocity (EROAVo-Va). In vitro validation was performed on a commercially available multifunctional valve tester with different size orifices and peak pressure gradients. A true EROA was derived through the regurgitant volume (RVol) calculated from the tester. For clinical validation, RVol was calculated as the difference between the overall stroke volume and the forward stroke volume of the right ventricle. Volumetric EROA was derived by dividing the RVol by the TR velocity-time integral (VTI). The vena contracta area (VCA) was obtained through direct planimetry with 3D echocardiography. The mean of volumetric EROA and VCA served as the reference in clinical validation. Results: Excellent correlation between the calculated EROAs and the true EROA was observed in vitro (r=0.98, r=0.97, and r=0.98 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively; all P values <0.0001). EROAVo-Va underestimated the true EROA and averaged 33% (P=0.3163), while EROA0.7 overestimated the true EROA and averaged 8% (P=0.0032). Clinically, these methods consistently exhibited a notable underestimation that varied with the reference EROA. This systematic underestimation was mitigated by both algorithms when either the VCA (biases of 19.6, 15.1, and 11.8 mm2 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively) or the volumetric EROA (biases of 10.1, 5.6, and 2.3 mm2 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively) served as the reference. Their ability to distinguish severe TR was similar, with area under the curve values of 0.905, 0.903, and 0.893 for uncorrected EROA, EROAVo-Va, and EROA0.7, respectively. No statistically significant differences were observed for diagnostic accuracy (all P values >0.05). Conclusions: Using a correction factor of 0.7 in quantifying TR provides similar accuracy when compared to other techniques. This represents a valuable clinical tool for quickly correcting the underestimation of the 2D PISA method in TR. This simple method may increase the frequency of applying the correction and earlier recognition of patients with severe TR.

Effect of left bundle branch pacing on right ventricular function: A 3-dimensional echocardiography study.

BACKGROUND: The effect of left bundle branch pacing (LBBP) on right ventricular (RV) function is not well known, and there is conflicting evidence regarding whether cardiac resynchronization therapy improves RV function. OBJECTIVES: The study aimed to investigate the effect of LBBP on RV function and to evaluate the response of RV dysfunction (RVD) to LBBP. METHODS: Sixty-five LBBP candidates were prospectively included in the study and underwent echocardiography at baseline and 6-month follow-up. LBBP response was left ventricular (LV) reverse remodeling, defined as a reduction in LV end-systolic volume of ≥15% at follow-up. RESULTS: Patients were assigned to 2 subgroups on the basis of 3-dimensional echocardiography-derived RV ejection fraction (EF) before LBBP implantation: 30 patients (46%) in the no RVD group and 35 patients (54%) in the RVD group. The RVD group was characterized by higher N-terminal pro-brain natriuretic peptide levels, New York Heart Association functional class, and larger LV/RV size. LBBP induced a significant reduction in QRS duration, LV size, and improvement in LVEF and mechanical dyssynchrony in both the no RVD and RVD groups, and a significant improvement in RV volumes and RVEF in the RVD group (all P<.01). LBBP resulted in a similar percentage reduction in QRS duration, LV dimensions, LV volumes, and percentage improvement in LVEF in RVD and no RVD groups (all P＞.05). LV reverse remodeling (29 of 35 patients vs 27 of 30 patients; P = .323) in the RVD group was similar to that in the no RVD group after LBBP. CONCLUSION: LBBP induces excellent electrical and mechanical resynchronization, with a significant improvement in RV volumes and function. RVD did not diminish the beneficial effects on LV reverse remodeling after LBBP.

Serum Uric Acid to Creatinine Ratio and Risk of Metabolic Syndrome in Patients with Overweight/Obesity.

Purpose: Metabolic syndrome (MetS) is a rising global concern with an increasing prevalence. This study aimed to evaluate the relationship between serum uric acid to creatinine ratio (SUA/Cr) and MetS in adults with overweight/obesity in China. Patients and Methods: We conducted a cross-sectional study comprising 4699 participants with overweight/obesity who underwent physical examinations. Their serum levels of various components, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), fasting plasma glucose (FPG), creatinine (Cr), and uric acid (UA) were measured. Renal function-normalized SUA was calculated using SUA/Cr. Logistic regression analysis was employed to investigate the association between SUA/Cr and MetS in adults with overweight/obesity. Results: SUA/Cr levels were lower in non-MetS participants (OR: 2.159, 95% CI: 1.82 to 2.56; p < 0.001), and tended to rise with the increasing number of MetS components. Additionally, elevated SUA/Cr levels were associated with a higher risk of hypertension, hyperglycemia, and dyslipidemia. Conclusion: SUA/Cr levels were significantly associated with MetS and its components in Chinese adults with overweight/obesity.

Echocardiographic parameters recommended for assessing the severity of tricuspid regurgitation: concordance and discordance.

Background: Current guidelines recommend integrating several echocardiographic indices to evaluate the severity of tricuspid regurgitation (TR). Discordance of indices, including qualitative and quantitative methods, commonly exists in practice. The discordance among these parameters has not yet been fully elucidated. Methods: A total of 127 patients with recognizable TR jets without pulmonary regurgitation or intracardiac shunt were prospectively enrolled. We evaluated 8 parameters by 2-dimensional (2D) echocardiography: proximal iso-velocity surface area (PISA)-derived regurgitant volume (RVol), PISA-derived effective regurgitant orifice area (EROA), PISA radius, vena contracta width (VCW), color Doppler jet area, tricuspid valve annular diameter, inferior vena cava (IVC) diameter, and peak E wave. According to current guidelines, each echocardiographic parameter was determined to represent either severe or non-severe TR. A concordance score was calculated as the number of concordant parameters divided by 8, with a higher score reflecting better concordance. Data were further categorized into 3 subgroups: complete concordance (0 discordant parameters), high concordance (1-2 discordant parameters), and low concordance (3-4 discordant parameters). Results: The mean concordance score was 81%±17% for the entire cohort. There were 48 (38%) patients with complete concordance, including 6 patients with severe TR. In contrast, the low concordance group (n=43, 34%) mostly comprised severe TR patients (36 patients). When considering only EROA, RVol, and VCW, concordance improved, with 98 patients (77%) in complete agreement. Conclusions: Concordance seems limited when using echocardiographic parameters to assess TR severity. Applying only EROA, RVol, and VCW results in better concordance, as recommended by the current guidelines.

Identifying Metabolic Syndrome Easily and Cost Effectively Using Non-Invasive Methods with Machine Learning Models.

Purpose: The objective of this study was to employ machine learning (ML) models utilizing non-invasive factors to achieve early and low-cost identification of MetS in a large physical examination population. Patients and Methods: The study enrolled 9171 participants who underwent physical examinations at Northern Jiangsu People's Hospital in 2009 and 2019, to determine MetS based on criteria established by the Chinese Diabetes Society. Non-invasive characteristics such as gender, age, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were collected and used as input variables to train and evaluate ML models for MetS identification. Several ML models were used for MetS identification, including logistic regression (LR), k-nearest neighbors algorithm (k-NN), naive bayesian (NB), decision tree (DT), random forest (RF), artificial neural network (ANN), and support vector machine (SVM). Results: Our ML models all showed good performance in the 10-fold cross-validation except for the SVM model. In the external validation, the NB model exhibited the best performance with an AUC of 0.976, accuracy of 0.923, sensitivity of 98.32%, and specificity of 91.32%. Conclusion: This study proposed a new non-invasive method for early and low-cost identification of MetS by using ML models. This approach has the potential to serve as a highly sensitive, convenient, and cost-effective tool for large-scale MetS screening.

Secondary leaflet tethering in patients with severe degenerative mitral regurgitation and its association with the severity of mitral regurgitation.

BACKGROUND: The purpose of the study was to determine the association between vena contracta area (VCA) and secondary leaflet tethering among mitral valve prolapse (MVP) patients, and thus to further identify and characterize an MVP with pathological leaflet tethering (MVPt+) phenotype. METHODS: We prospectively evaluated 94 consecutive MVP patients with significant mitral regurgitation (MR) and 21 healthy controls. MVPt+ group was defined as tenting volume index (TVi) > .7 mL/m2 . The three-dimensional (3D) geometry of mitral valve apparatus and VCA was measured with dedicated quantification software. RESULTS: Of the 94 patients with MVP and significant MR, 31 patients showed a TVi > .7 mL/m2 and entered the MVP with leaflet tethering (MVPt+) group. In stepwise multivariate analysis, only prolapse volume index and TVi were independently associated with 3D VCA. 3D VCA, annular area index, and plasma levels of NT-proBNP were independently correlated with the severity of leaflet tethering. ROC curve revealed that a 3D VCA ≥ .55 cm2 is the optimal cutoff point to predict MVPt+ phenotype. CONCLUSIONS: Secondary leaflet tethering is a significant mechanism behind severe degenerative MR, resulting in an MVPt+ phenotype featuring more advanced morphological and hemodynamical characteristics.

Correlation of multiple lipid and lipoprotein ratios with nonalcoholic fatty liver disease in patients with newly diagnosed type 2 diabetic mellitus: A retrospective study.

Background and objective: The diagnostic value of lipid and lipoprotein ratios for NAFLD in newly diagnosed T2DM remains unclear. This study aimed to investigate the relationships between lipid and lipoprotein ratios and the risk of NAFLD in subjects with newly diagnosed T2DM. Methods: A total of 371 newly diagnosed T2DM patients with NAFLD and 360 newly diagnosed T2DM without NAFLD were enrolled in the study. Demographics variables, clinical history and serum biochemical indicators of the subjects were collected. Six lipid and lipoprotein ratios, including triglycerides to high-density lipoprotein-cholesterol (TG/HDL-C) ratio, cholesterol to HDL-C (TC/HDL-C) ratio, free fatty acid to HDL-C (FFA/HDL-C) ratio, uric acid to HDL-C (UA/HDL-C) ratio, low-density lipoprotein-cholesterol to HDL-C (LDL-C/HDL-C) ratio, apolipoprotein B to apolipoprotein A1 (APOB/A1) ratio, were calculated. We compared the differences in lipid and lipoprotein ratios between NAFLD group and non-NAFLD group, and further analyzed the correlation and diagnostic value of these ratios with the risk of NAFLD in the newly diagnosed T2DM patients. Results: The proportion of NAFLD in patients with newly diagnosed T2DM increased progressively over the range Q1 to Q4 of six lipid ratios, including the TG/HDL-C ratio, TC/HDL-C ratio, FFA/HDL-C ratio, UA/HDL-C ratio, LDL-C/HDL-C ratio, and APOB/A1 ratio. After adjusting for multiple confounders, TG/HDL-C, TC/HDL-C, UA/HDL-C, LDL-C/HDL-C and APOB/A1 were all strongly correlated with the risk of NAFLD in patients with newly diagnosed T2DM. In patients with newly-onset T2DM, the TG/HDL-C ratio was the most powerful indicator for the diagnosis of NAFLD among all six indicators, with an area under the curve (AUC) of 0.732 (95% CI 0.696-0.769). In addition, TG/HDL-C ratio>1.405, with a sensitivity of 73.8% and specificity of 60.1%, had a good diagnostic ability for NAFLD in patients with newly diagnosed T2DM. Conclusions: The TG/HDL-C ratio may be an effective marker to help identify the risk of NAFLD in patients with newly diagnosed T2DM.

Real-Time Monitoring and Step-by-Step Guidance for Transcatheter Tricuspid Annuloplasty Using Transesophageal Echocardiography.

Transcatheter tricuspid valve intervention (TTVI) is a novel alternative to functional tricuspid regurgitation (FTR) for patients with prohibitive surgical risk. Devices have been designed according to different pathophysiological mechanisms of FTR, including ones to achieve an edge-to-edge repair and others aiming at direct annuloplasty. Recently, a transcatheter tricuspid valve repair system mimicking a surgical Kay procedure (K-Clip™ system, Huihe Medical Technology, Shanghai, China) completed its salvage-use trial. The system, which clips the posterior annulus to achieve bicuspidization of the TV, demonstrated acceptable procedural safety and efficacy. Each TTVI system has distinct characteristics for echocardiographic imaging and special consideration for intraoperative guidance. This review focuses on elaborating how two-dimensional and three-dimensional transesophageal echocardiography (TEE) are used in clinical practice to guide K-Clip™ implantation in comparison to other direct annular reduction devices. A limited number of TEE work planes are proposed for the procedure with the aim to provide a steeper learning curve for the echocardiographer and interventionalist while simplifying the implantation steps.

Semaglutide May Alleviate Hepatic Steatosis in T2DM Combined with NFALD Mice via miR-5120/ABHD6.

Objective: Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has been extensively studied, the role of its underlying pathogenesis remains unclear, and there is currently no approved therapeutic strategy for NAFLD. The purpose of this study was to observe the beneficial effects of Semaglutide on NAFLD in vivo and in vitro, as well as its potential molecular mechanisms. Methods: Semaglutide was used to treat type 2 diabetes mellitus (T2DM) combined with NAFLD mice for 12 weeks. Hepatic function and structure were evaluated by liver function, blood lipids, liver lipids, H&E staining, oil red staining and Sirius staining. The expression of α/ß hydrolase domain-6 (ABHD6) was measured by qPCR and Western blotting in vivo and in vitro. Then, dual-luciferase reporter assay was performed to verify the regulation of the upstream miR-5120 on ABHD6. Results: Our data revealed that Semaglutide administration significantly improved liver function and hepatic steatosis in T2DM combined with NAFLD mice. Furthermore, compared with controls, up-regulation of ABHD6 and down-regulation of miR-5120 were found in the liver of T2DM+NAFLD mice and HG+FFA-stimulated Hepa 1-6 hepatocytes. Interestingly, after Semaglutide intervention, ABHD6 expression was significantly decreased in the liver of T2DM+NAFLD mice and in HG+FFA-stimulated Hepa 1-6 hepatocytes, while miR-5120 expression was increased. We also found that miR-5120 could regulate the expression of ABHD6 in hepatocytes, while Semaglutide could modulate the expression of ABHD6 through miR-5120. In addition, GLP-1R was widely expressed in mouse liver tissues and Hepa 1-6 cells. Semaglutide could regulate miR-5120/ABHD6 expression through GLP-1R. Conclusion: Our data revealed the underlying mechanism by which Semaglutide improves hepatic steatosis in T2DM+NAFLD, and might shed new light on the pathological role of miR-5120/ABHD6 in the pathogenesis of T2DM+NAFLD.

Clinical characteristics and risk factors analysis of viral shedding time in mildly symptomatic and asymptomatic patients with SARS-CoV-2 Omicron variant infection in Shanghai.

Objective: To analyze the clinical characteristics and risk factors of viral shedding time in mildly symptomatic and asymptomatic patients with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (BA.2 and BA2.2) infection in Shanghai, and the effect of traditional Chinese medicine (TCM) treatment, so as to provide a reference basis for epidemic prevention, control and clinical treatment. Methods: A total of 6,134 asymptomatic or mildly symptomatic Omicron-infected patients admitted to Tianhua Road fangcang shelter hospital in Jinshan, Shanghai, between April 2022 and May 2022 were included. Demographic characteristics and clinical histories were collected and compared in subgroups according to the different durations of viral shedding. Spearman's correlation analysis was performed to explore the association between virus shedding time and clinical variables. Multiple linear regression was used to evaluate the risk factors for viral shedding time. Result: Most patients with asymptomatic and mildly symptomatic Omicron infection were male, and more than half of patients had a viral shedding time of 8-15 days. The patients were divided into three groups according to the time of viral shedding: short-duration (≤ 7 days), intermediate-duration (8-15 days) and long-duration group (≥16 days). The proportion of patients aged ≤ 29 years was the highest in the short-duration group (30.2%), whereas the proportion of patients aged 50-64 yeas was the highest in the long-duration group (37.9%). The proportion of patients with the chronic non-communicable diseases among the short-, intermediate- and long-duration groups was 6.2, 9.4, and 14.9%, respectively. Among them, hypertension was the most found (4.9, 7.8, and 11.7%, respectively). By multivariate analyses, we identified that viral shedding time of Omicron variants was independently negatively correlated with male patients, TCM treatment, and manual laborers, while it was independently positively associated with age and hypertension. Additionally, TCM treatment could significantly shorten the length of viral shedding time, especially for men, age ≥30 years, comorbid chronic non-communicable diseases, unemployed people and manual worker. Conclusions: Our results suggested that age and hypertension were independent risk factors for the duration of viral shedding in asymptomatic and mildly symptomatic omicron infected patients. TCM can effectively shorten viral shedding time.

Pericardial Effusion During the Perioperative Period for Left Atrial Appendage Closure.

Objectives: To analyze the predictors of pericardial effusion (PE) during the perioperative period of the left atrial appendage closure procedure in our center. Methods: A total of 624 consecutive patients with non-valvular AF undergoing LAAC from May 2014 to October 2019 were involved in this study. Patients were divided into groups depending on whether they showed no PE, intraoperative PE or postoperative PE. We analyzed the predictors of PE during the perioperative period of the LAAC procedure. Results: (1) Of the 624 patients in our population (age 68.2 ± 9.1 years, 63% male, CHA2DS2-VASc score 3.4 ± 1.6), 30 patients experienced PE in the perioperative period, including 10 intraoperative PE and 20 postoperative PE. (2) A total of 26 (86.6%) patients had mild PE. 4 (13.4%) patients had pericardial tamponade, 2 (6.7%) of which were intraoperative, and the other 2 (6.7%) postoperative. (3) Significant differences were measured in relation to female sex, intraoperative time, combined procedures, changes in sinus rhythm, device retrieval times and duration of hospitalization between 2 groups (no PE occurred, intraoperative PE), P values were 0.039, 0.024, 0.004, 0.015, 0.003 and 0.039. Conclusions: Female sex, paroxysmal AF, changing in sinus rhythm, device retrieval times and intraoperative time all had a positive association with PE during the perioperative period.

Impact of Leaflet Tethering on Residual Regurgitation in Patients With Degenerative Mitral Disease After Interventional Edge-to-Edge Repair.

Background: Grade 2+ residual mitral regurgitation (MR 2+) is associated with the recurrence of MR and a lower survival rate in interventional mitral valve (MV) edge-to-edge (EE) repair. We sought to determine the MV anatomic factors affecting residual MR 2+ during interventional EE repair with the ValveClamp system in patients with degenerative MR (DMR). Methods: In this multicenter study, 62 patients with significant (grade 3+ to 4+) DMR underwent ValveClamp implantation across eight centers from July 2018 to December 2019. Patient clinical, anatomical, and procedural characteristics were prospectively collected and retrospectively analyzed. Results: A single clamp was implanted in 59 patients, and two clamps were implanted in three patients. Residual MR 2+ was found in 14 patients (22.6%) immediately after the ValveClamp procedure. Patients with residual MR 2+ showed significantly larger preoperative tenting sizes and annular dimensions than the residual MR ≤1+ group. Multivariate analysis identified tenting volume as the major determinant of residual MR 2+ after ValveClamp procedures (odds ratio, 1.410 per 0.1-mL/m2 increase; 95% confidence interval, 1.167-1.705; P < 0.001). Receiver operating characteristic curves identified a tenting volume index ≥0.82 mL/m2 as the optimal cutoff point to predict residual MR 2+ (area under curve, 0.84). Patients with a tenting volume index ≥0.82 mL/m2 were more likely to develop recurrent 3+ MR or undergo MV surgery during short-term follow-up (P < 0.001). Conclusions: Preoperative assessment of the tenting volume index will help to predict intraoperative residual MR 2+ in patients with DMR receiving EE-based interventional repair. Improvements in the interventional strategy are warranted for sustained MR reduction in patients with DMR with unfavorable anatomy.

Clinical outcomes of bivalirudin versus heparin in atrial fibrillation patients undergoing percutaneous left atrial appendage occlusion.

BACKGROUND: Prior studies have suggested that patients with atrial fibrillation (AF) referred for left atrial appendage occlusion (LAAO) are confronted with considerable risk of periprocedural thromboembolism and hemmorhagic events. The purpose of this study was to evaluate the safety and feasibility of bivalirudin during LAAO. METHODS: This retrospective, observational study included 420 AF patients who were evaluated as being at high risk of stroke or bleeding and indicated for LAAO at our center between June 2018 and June 2019 (158 with bivalirudin and 262 with heparin). The primary outcome was the incidence of any bleeding within 48 hours of LAAO. Secondary outcomes were major adverse cardiac events (MACE) between 48 hours and 60 days post-procedure and overall bleeding events during follow up. RESULTS: No significant difference was observed between bivalirudin and heparin for major periprocedural bleeding (1.27% for bivalirudin vs. 2.29% for heparin, P=0.716) or minor bleeding (1.27% vs. 1.15%, P>0.9). At 48 hours post-procedure, strokes occurred at a rate of 0.63% in the bivalirudin group and 1.15% in the heparin group (P>0.9), and one case treated with bivalirudin developed systemic embolization. At 60 days, the rates of MACE (1.90% vs. 2.29%, P>0.9), a device-related thrombus (DRT) (1.27% vs. 1.52%, P>0.9), and overall bleeding events (5.06% vs. 4.96%, P=0.963) were comparable between the 2 cohorts. Upon Kaplan-Meier survival analysis, early safety during the 60-day follow-up was 93.67% in the bivalirudin group and 91.60% in the heparin group (P=0.570). CONCLUSIONS: Bivalirudin has a comparable safety and efficacy profile to heparin as an intraprocedural anticoagulant, but currently, it should still be reserved for patients in which heparin is contraindicated.

Impact of Thrombocytopenia in Patients With Atrial Fibrillation Undergoing Left Atrial Appendage Occlusion: A Propensity-Matched Comparison of 190 Consecutive Watchman Implantations.

Objectives: The purpose of this study was to provide data on the long-term efficacy and safety of left atrial appendage occlusion (LAAO) in patients with atrial fibrillation (AF) and chronic thrombocytopenia (cTCP). Methods: Between January 2016 and December 2018, a total of 32 AF patients with thrombocytopenia (platelet count <100*10∧9/L) undergoing LAAO at our center were identified and their outcomes were compared with a propensity-matched cohort (match ratio 1:5) of patients without cTCP who had also been indicated for LAAO. Results: Between the cTCP patients and the control group, no difference was found on the incidence of stroke (0 vs. 3.13%, p = 0.592), systematic thromboembolisation (0 vs. 0.63%, p > 0.9) and device-related thrombus (DRT) (3.13 vs. 2.50%, p > 0.9). Major (12.50 vs. 3.75%, p = 0.065) and minor bleeding (15.63 vs. 1.25%, p = 0.002) was more frequent in cTCP patients but no statistical difference was reached in major bleeding. Moreover, thrombocytopenia was also identified as an independent predictor of any bleeding events (OR: 8.150, 95% CI: 2.579-25.757, p < 0.001), while an inverse relationship between higher absolute platelet count and stroke events was revealed (OR: 1.015; 95% CI: 1.002~1.029, p = 0.022). However, in both groups we saw a significant reduction in observed annualized rates of non-procedural complications compared with the predicted values. In the cTCP and control groups, clinical thromboembolism was reduced by 100 and 74.32%, and major bleeding by 42.47 and 71.67%, respectively. Conclusion: Our preliminary results indicate that LAAO using the Watchman device could be a safe and effective means of preventing stroke in AF patients with or without thrombocytopenia, but bleeding complications should be monitored intensively in cTCP patients.

Comparison of fluoroscopy and transesophageal echocardiogram for intra-procedure device surveillance assessment during implantation of Watchman.

OBJECTIVES: To evaluate intraprocedural assessments using transesophageal echocardiography (TEE) and fluoroscopy during left atrial appendage occlusion (LAAO) with the WATCHMAN device. METHOD: A total of 208 patients with non-valvular atrial fibrillation (AF) undergoing LAAO were included in this study[101 standard procedures (retrospective cohort) and 107 with fluoroscopy-alone approach (prospective cohort). Individual device position, anchoring, compression and peri-device leak (PDL) were successively analyzed based on TEE and fluoroscopy in the retrospective cohort to summarize detailed fluoroscopic assessments for prospective application. Clinical outcomes were assessed between two cohorts. RESULTS: For retrospective cohort, TEE and fluoroscopy agreed on device position and anchoring. Compression upon fluoroscopy was well correlated with 2D-TEE (r = 0.908) and the difference in overall detection of PDL was not statistically significant between two imaging modalities (p = 0.304). For the prospective cohort with fluoroscopy-guidance alone, implantation success was similar to that of the retrospective cohort (98.13% vs 100%, p = 0.498). The incidence rate of major clinical adverse events was relatively higher in prospective cohort during hospitalization and follow-up but did not reach significant difference (5.61% vs 1.98%; 0.99% vs 0.93%, p > 0.05). Moreover, the prospective group presented with shorter procedural duration, shorter in-hospital stay and lower total hospitalization cost than retrospective group. CONCLUSION: LAAO performed by experienced operators in large volume centers is feasible under fluoroscopy guidance. However, there is still a trend in favor of TEE for greater procedural safety and more complete LAA seal. We suggest that this minimalist approach could be proposed in cases with contraindication to general anesthesia and/or TEE.

Sources of Variability in Vena Contracta Area Measurement for Tricuspid Regurgitation Severity Grading: Comparison of Technical Settings and Vendors.

BACKGROUND: Previous studies found different cutoffs of vena contracta area (VCA) to define severe tricuspid regurgitation (TR). The aim of this study was to investigate the factors associated with such variability by comparing technical variables and vendors. METHODS: Sixty-nine patients with scheduled tricuspid surgery were included in this prospective study. For each patient, TR data sets were obtained on three-dimensional color Doppler transthoracic echocardiography on at least two of three systems: GE Vivid E95 (n = 39), Siemens SC2000 Prime (n = 64), and Philips EPIQ 7C (n = 60). VCA was measured using default settings or with color baseline shifted on all three platforms and with minimal color gain (10%-20%) on the GE platform. RESULTS: Color gain reduction and baseline shift caused significant change sin VCA measurement (-46% and 10%, respectively). Intervendor comparison exhibited wide limits of agreement (narrowest range, -74% to 167%), with either default or optimized settings. Different technical settings, platforms, and reference methods all produced different VCA cutoffs for severe TR. CONCLUSIONS: VCA measurement in TR is sensitive to technical factors and demonstrates intervendor variability. Technical variables in VCA measurement should be reported in detail to allow comparison among research studies. The same vendor and settings should be used for longitudinal analysis of TR VCA in the same patient in multivendor echocardiography laboratories.

Reference value of perimeter-derived diameter assessed by three-dimensional transesophageal echocardiography in left atrial appendage occluder size selection.

BACKGROUND: The aim of this study was to investigate the utility of perimeter-derived diameter (PDD) measured by three-dimensional (3D) transesophageal echocardiography (TEE) in predicting the size of left atrial appendage (LAA) occluder. METHODS AND RESULTS: Left atrial appendage landing zone diameter (LZD) was measured by two-dimensional (2D) TEE, 3DTEE, and digital subtraction angiography (DSA) as LZD-2Dmax, LZD-2Dmean, LZD-3Dmax, LZD-3Dmean, LZD-PDD, LZD-DSAmax, respectively, before and during transcatheter LAA closure with Watchman devices in 100 patients. A difference of one or more device size intervals between the predicted size and the size actually implanted was defined as mismatching. Seventy-eight patients were followed up by TEE to obtain occluder compression ratio. The correlation between LZD and the final implanted occluder size was 0.559, 0.641, 0.754, 0.760, 0.782, and 0.848 for LZD-2Dmax, LZD-2Dmean, LZD-3Dmax, LZD-3Dmean, LZD-PDD and LZD-DSAmax, respectively (P < .001). Matching ratio between the size predicted by retrospective measurements of LZD and the device size actually implanted was 65%, 57%, 66%, 63%, 70%, and 83% for LZD-2Dmax, LZD-2Dmean, LZD-3Dmax, LZD-3Dmean, LZD-PDD and LZD-DSAmax, respectively. There was no significant difference in LZD value, matching ratio, and compression ratio between the patients with eccentric and noneccentric LAA landing zone (P > .05). Compression ratio of the mismatching subjects was higher than that in the matching subjects when evaluated by LZD-2Dmean, LZD-3Dmean, and LZD-PDD (P < .05). CONCLUSIONS: Landing zone diameter derived from LAA perimeter measured by preprocedure 3DTEE showed reference value for LAA occluder size selection, providing superior correlation and matching ratio with the final implanted size and indicating the adjustment of oversizing.

Three-dimensional transthoracic echocardiographic evaluation of tricuspid regurgitation severity using proximal isovelocity surface area: comparison with volumetric method.

BACKGROUND: The quantification of tricuspid regurgitation(TR) using three-dimensional(3D) proximal isovelocity surface area (PISA) derived effective regurgitant orifice area (EROA) is feasible in functional TR. The aim of our study was to explore the diagnostic accuracy and utility of 3D PISA EROA in a larger population of different etiologies. METHODS: One hundred and seven patients with confirmed TR underwent 2D and 3D transthoracic echocardiography (TTE). 3D PISA EROA was calculated and EROA derived from 3D regurgitant volume (Rvol) was used as the reference. RESULTS: 3D PISA EROA showed better correlation in primary TR than in functional TR(r = 0.897, P < 0.01). 3D PISA EROA differentiated severe TR with comparable accuracy in patients with primary and functional etiology (Z-value 16.506 vs 21.202), but with different cut-offs (0.49cm2 vs. 0.41 cm2). The chi-square value for incorporated clinical symptoms, positive echocardiographic results and 3D PISA EROA to grade severe TR was higher than only included clinical symptoms or incorporated clinical symptoms and positive echocardiographic results (chi-square value 137.233, P < 0.01). CONCLUSION: TR quantification using 3D PISA EROA is feasible and accurate under different etiologies. It has incremental diagnostic value for evaluating severe TR.