2-year results and myocardial impact of transapical mitral valve repair in patients with primary mitral regurgitation: an echocardiographic study.

BACKGROUND: There is limited data on the 2-year outcomes of transapical transcatheter edge-to-edge repair (TA-TEER) using the ValveClamp in patients with severe primary mitral regurgitation (MR) and its impact on myocardial deformation. METHODS: From July 2018 to March 2021, 53 patients with symptomatic severe primary MR underwent TA-TEER were enrolled. The endpoint was the composite of all-cause mortality, recurrent 3 + or 4 + MR, or need for mitral surgery. RESULTS: Among the 53 patients who had successfully ValveClamp implantation, 8(15.1%) reached the composite endpoint. Significant improvement in left ventricular (LV) end-diastolic volume, pulmonary artery systolic pressure, NYHA functional class, and MR severity were observed (P < 0.05 for all). Univariate Cox's regression analysis revealed that LV end-diastolic volume index, LV end-systolic volume index, left atrial volume index, and pulmonary artery systolic pressure were associated with adverse events (P < 0.05 for all). On multivariate Cox regression analysis, left atrial volume index was independently associated with the endpoint (hazard ratio, 1.049; 95% CI, 1.009-1.091; P < 0.001) after adjustment for above echocardiographic parameters. LV global longitudinal strain and apical longitudinal strain in global and regional segments decreased at 30 days, but showed a recovery at 2 years with no significant difference compared to the baseline. CONCLUSION: TA-TEER using the ValveClamp presented favorable safety and efficacy at 2-year. Myocardial deformation impairment was observed at 30 days post-procedure, but did not persist at 2 years.

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.

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.

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.

Comparison of the Acute Effects of Different Pacing Sites on Cardiac Synchrony and Contraction Using Speckle-Tracking Echocardiography.

Background: Cardiac pacing in patients with bradyarrhythmia may employ variable pacing sites, which may have different effects on cardiac function. Left bundle branch pacing (LBBP) is a new physiological pacing modality, and the acute outcomes on cardiac mechanical synchrony during LBBP remain uncertain. We evaluated the acute effects of four pacing sites on cardiac synchrony and contraction using speckle-tracking echocardiography, and comparisons among four different pacing sites were rare. Methods: We enrolled 21 patients with atrioventricular block or sick sinus syndrome who each sequentially underwent acute pacing protocols, including right ventricular apical pacing (RVAP), right ventricular outflow tract pacing (RVOP), His bundle pacing (HBP), and left bundle branch pacing (LBBP). Electrocardiograms and echocardiograms were recorded at baseline and during pacing. The interventricular mechanical delay (IVMD), the standard deviation of the times to longitudinal peak strain during 17 segments (PSD), and the Yu index were used to evaluate ventricular mechanical synchrony. Layer-specific strain was computed using two-dimensional speckle tracking technique to provide in-depth details about ventricular synchrony and function. Results: Left ventricular ejection fraction (LVEF) and tricuspid annulus plane systolic excursion (TAPSE) were significantly decreased during RVAP and RVOP but were not significantly different during HBP and LBBP compared with baseline. RVAP and RVOP significantly prolonged QRS duration, whereas HBP and LBBP showed non-significant effects. IVMD and PSD were significantly increased during RVAP but were not significantly different during RVOP, HBP, or LBBP. LBBP resulted in a significant improvement in the IVMD and Yu index compared with RVAP. No significant differences in mechanical synchrony were found between HBP and LBBP. Conclusion: Among these pacing modalities, RVAP has a negative acute impact on cardiac synchrony and contraction. HBP and LBBP best preserve physiological cardiac synchrony and function.

Immediate Renal Denervation After Acute Myocardial Infarction Mitigates the Progression of Heart Failure via the Modulation of IL-33/ST2 Signaling.

Objective: Previous studies have demonstrated the protective effects of renal denervation (RDN) in pre-existing heart failure, but the effects of immediate RDN after acute myocardial infarction (AMI) on subsequent cardiac remodeling have not been reported. This study aimed to investigate the cardioprotective effects of immediate RDN after AMI and its underlying mechanism. Methods: AMI was induced by intracoronary gelatin sponge embolization in 14 Shanghai white pigs that were randomized to undergo either renal angiography (AMI+sham group) or RDN (AMI+RDN group) after 1 h of hemodynamic monitoring. Cardiac function of the two groups was measured at baseline, 1 h post-AMI and at the 1 month follow-up (1M-FU) by transthoracic echocardiography (TTE). Plasma NT-proBNP, soluble ST2 (sST2), norepinephrine (NE), and renin-angiotensin-aldosterone system activity were detected simultaneously. The renal cortex was harvested for NE measurement after the 1M-FU, and the renal arteries were stained with tyrosine hydroxylase for the evaluation of sympathetic activity. Heart tissues in the non-ischemic areas were collected to assess histological and molecular left ventricular (LV) remodeling by pathological staining, RT-PCR, and western blotting. Results: There was no difference in the hemodynamic stability or cardiac function between the two groups at baseline and 1 h post-AMI. Six pigs from each of the two groups completed the 1M-FU. TTE analysis revealed the improved cardiac function of immediate RDN in the AMI+RDN group and circulating NT-proBNP levels were lower than those in the AMI+sham group. Further analysis showed significantly less interstitial fibrosis in the remote non-ischemic myocardium after immediate RDN, together with decreased cardiomyocyte hypertrophy and inflammatory cell infiltration. sST2 levels in circulating and myocardial tissues of animals in the AMI+RDN group were significantly higher than those in the AMI+sham group, accompanied by corresponding alterations in IL-33/ST2 and downstream signaling. Conclusions: Immediate RDN can improve cardiac function and myocardial remodeling after AMI via modulation of IL-33/ST2 and downstream signaling.

Real-Time Monitoring and Step-by-Step Guidance for Transapical Mitral Valve Edge-to-Edge Repair Using Transesophageal Echocardiography.

MitraClip edge-to-edge (E2E) repair system is the only transcatheter device recommended in the current guidelines for treating mitral regurgitation (MR). The percutaneous femoral venous transseptal access of MitraClip requires a complex steerable delivery system and may thus be technically complex to optimally position and deploy the clip onto the mitral valve. A transapical approach for E2E repair has been devised to treat MR for the ease of operation (ValveClamp system, Hanyu Medical Technology, Shanghai). The first-in-human study of ValveClamp has demonstrated its early feasibility and effectiveness for the treatment of patients with degenerative MR. Transesophageal echocardiography (TEE) is the only imaging modality required for intraoperative guidance of ValveClamp implantation. Successful implantation depends on accurate localization and orientation of the clamp and efficient intraoperative communication between the echocardiographer and the intervention team. Thus, the focus of this review is on elaborating how two-dimensional (2D) and three-dimensional (3D) TEE are used in clinical practice to guide ValveClamp implantation and it may facilitate the understanding of simplicity and safety of this novel procedure. We also describe the implementation of several novel advancements in 3D TEE imaging, which improve the confidence of image interpretation for intraoperative guidance and expedite implantation times.

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.

Effect of a novel transcatheter edge-to-edge repair device on the three-dimensional geometry of mitral valve in degenerative mitral regurgitation.

OBJECTIVES: We sought to assess the acute intraprocedural effects of the ValveClamp system in DMR patients on the mitral valve (MV) three-dimensional (3D) geometry and the association of these effects with mitral regurgitation (MR) reduction. BACKGROUND: Few data are available about the specific impact of transcatheter edge-to-edge repair in patients with degenerative mitral regurgitation (DMR). METHODS: Thirty-five symptomatic patients (age 74.26 ± 6.61 years) with Grade 3 to 4+ degenerative MR underwent 3D transoesophageal echocardiography (TEE) during ValveClamp implantation. Volumetric data sets were retrospectively analyzed using mitral valve quantitative 3D modeling software. RESULTS: Mitral valve annular anterior-posterior (AP) diameter decreased from 33.24 ± 4.03 to 31.12 ± 3.66 mm (p < .001), and prolapse height from 4.78 ± 2.19 to 2.32 ± 1.92 mm (p < .001), and total exposed leaflet area from 1,110.29 ± 224.21 mm2 to 1,013.44 ± 228.71 mm (p = .004). Accordingly, we observed a significant reduction of MR severity after ValveClamp implantation. Multivariable analysis revealed postprocedural MR reduction was associated with shortening in anterior-posterior diameter (coefficient 0.427, p = .008) and reduction in prolapse height (coefficient 0.369, p = .021). CONCLUSIONS: ValveClamp implantation exerts an acute effect on the 3D MV geometry. Postprocedural reduction in AP diameter and reduction in prolapse height correlates with MR downgrading in patients with degenerative MR.

The Effect of a Novel Transcatheter Edge-to-Edge Mitral Valve Repair Device in a Porcine Model of Mitral Regurgitation.

BACKGROUND: A new technique has been developed for treating mitral regurgitation (MR) via a transapical approach, which encompasses an easy-to-use leaflet clamp and a smaller-sized delivery system (14F-16F). OBJECTIVES: We aimed to evaluate the effectiveness of this device in a porcine model of acute MR. METHODS: Acute MR was induced in 36 anesthetized porcine subjects by severing the chordae supporting the corresponding segment of the leaflet. The ValveClamp system was then transapically implanted on the prolapsing segment under epicardial echocardiographic guidance. Echocardiographic assessments were performed before and after the transapical interventions. All of the animals were killed 30 days after the procedure to verify the proper location of the implanted devices. RESULTS: Epicardial echocardiography revealed severe MR (n = 26) or moderate to severe MR (n = 10) in the pig model of acute MR. Overt MR reduction was observed following the procedure through echocardiography; residual MR was absent in 10 cases, mild in 17 cases, and moderate in 9 cases. There was no evidence of mitral stenosis at the end of the procedure in terms of mitral valve area and mitral valve pressure gradient. Autopsy demonstrated that all ValveClamp devices were precisely placed to clamp the prolapsing segment of the mitral valve. CONCLUSIONS: Transapical implantation of the ValveClamp device under epicardial echocardiographic guidance was effective and safe in reducing acutely induced MR in this pig model. It is potentially applicable as a novel user-friendly transcatheter edge-to-edge mitral valve repair device for the treatment of MR in humans.

Prediction of carbohydrate-binding proteins from sequences using support vector machines.

Carbohydrate-binding proteins are proteins that can interact with sugar chains but do not modify them. They are involved in many physiological functions, and we have developed a method for predicting them from their amino acid sequences. Our method is based on support vector machines (SVMs). We first clarified the definition of carbohydrate-binding proteins and then constructed positive and negative datasets with which the SVMs were trained. By applying the leave-one-out test to these datasets, our method delivered 0.92 of the area under the receiver operating characteristic (ROC) curve. We also examined two amino acid grouping methods that enable effective learning of sequence patterns and evaluated the performance of these methods. When we applied our method in combination with the homology-based prediction method to the annotated human genome database, H-invDB, we found that the true positive rate of prediction was improved.