Deletion of TECRL promotes skeletal muscle repair by up-regulating EGR2.

Myogenic regeneration relies on the proliferation and differentiation of satellite cells. TECRL (trans-2,3-enoyl-CoA reductase like) is an endoplasmic reticulum protein only expressed in cardiac and skeletal muscle. However, its role in myogenesis remains unknown. We show that TECRL expression is increased in response to injury. Satellite cell-specific deletion of TECRL enhances muscle repair by increasing the expression of EGR2 through the activation of the ERK1/2 signaling pathway, which in turn promotes the expression of PAX7. We further show that TECRL deletion led to the upregulation of the histone acetyltransferase general control nonderepressible 5, which enhances the transcription of EGR2 through acetylation. Importantly, we showed that AAV9-mediated TECRL silencing improved muscle repair in mice. These findings shed light on myogenic regeneration and muscle repair.

Study design and rationale of COMPETE: Comparison of the effect of medication therapy in alleviating migraine with patent foramen ovale.

BACKGROUND: Previous studies have examined the impact of antithrombotic agents on Patent Foramen Ovale (PFO) in relation to migraine. However, differences in effectiveness of different antithrombotic agents and traditional migraine medications are not known. METHODS/DESIGN: This study is an investigator-initiated, randomized, multicenter, single-masked (outcomes assessor), and active-controlled parallel-group trial (ClinicalTrials.gov Identifier: NCT05546320), with the objective of evaluating the prevention efficacy of antithrombotic agents compared to first-line migraine medication in PFO patients. The trial involves 1,000 migraine patients with a right-to-left shunt at the atrial level, randomized in a 1:1:1:1 fashion to receive either aspirin 300 mg QD, clopidogrel 75 mg QD, rivaroxaban 20 mg QD, or the active-control metoprolol 25 mg BID. The primary efficacy end point is the response rate, defined as a 50% or greater reduction in the average migraine attack days per month or in the average number of migraine attacks per month at 12-week visit compared to baseline. CONCLUSIONS: The COMPETE trial aims to provide valuable insights into the comparative effectiveness of antithrombotic agents and standard migraine therapies in patients with PFO. This study holds the promise of advancing treatment approaches for individuals having migraines associated with PFO, thus addressing an important gap in current migraine management strategies.

Successful treatment of severe primary mitral regurgitation due to rheumatic aetiology using a novel-designed transcatheter edge-to-edge repair system.

The transcatheter edge-to-edge mitral valve repair (TEER) has been recommended as a reliable treatment option for selected patients with severe degenerative and functional mitral regurgitation (MR). Although MR patients with rheumatic etiology were excluded from two significant trials (EVEREST II and COAPT) that established a role for the TEER in degenerative and functional MR. However, it has been reported that the TEER procedure could be safely and effectively performed in carefully selected rheumatic MR patients. Therefore, we share a case report of successfully treating severe rheumatic MR using a novel-designed TEER system (JensClipTM).

Outcomes of Transcatheter Closure of Congenital Left Circumflex Coronary Artery Fistula.

BACKGROUND: Congenital left circumflex coronary artery fistula (LCX-CAF) is a relatively rare type of coronary artery fistula (CAF); little is known about the outcomes of transcatheter closure (TCC) of LCX-CAF.Methods and Results: All consecutive patients admitted to Fuwai Hospital and scheduled for TCC of LCX-CAF between January 2012 and December 2022 were reviewed retrospectively. Of the 25 consecutive patients (mean [±SD] age 34±20 years; 48% male) admitted and scheduled for TCC of congenital LCX-CAF, the procedure was feasible in 22 (77.3%). The mean (±SD) diameter of the fistulas was 6.99±2.04 mm; 21 (84%) patients had a large fistula (i.e., diameter >2-fold greater than non-feeding coronary artery). Occluders were deployed via a transarterial approach and arteriovenous loop in 6 (27.3%) and 16 (72.7%) patients, respectively. No procedural complications were recorded. Although the procedural success rates are similar for single LCX-CAF and left anterior descending CAF (81.25% vs. 92.86%; P=0.602), the mean time from initial angiography to first occluder deployment is significantly longer for LCX-CAF (83.06±36.07 vs. 36.00±9.49 min; P<0.001). The mean (±SD) follow-up time was 62.2±45.5 months. The incidence of myocardial infarction and recanalization of the fistula was 4.5% (1/22) and 9.1% (2/22), respectively. CONCLUSIONS: TCC of LCX-CAF is a feasible and effective alternative to surgical repair, with comparable outcomes in selected patients. Optimal medical therapy to prevent post-closure myocardial infarction requires further investigation.

Assessing the State of Training in Congenital Interventional Cardiology: A Global Survey of Program Directors.

This study aimed to evaluate the current state of congenital interventional cardiology training worldwide, with a focus on case volumes, competency assessment, and the need for ongoing mentorship during early career stages. A survey was conducted among program directors (PDs) of congenital interventional training programs across the globe. The survey gathered data on training pathways, case volumes, types of procedures performed, trainee competency assessment, and the role of ongoing mentorship. Of the 79 PDs who completed the survey, it was observed that training pathways and case volumes varied significantly, particularly between the United States and other countries. Most PDs reported an annual laboratory case volume of >500 congenital cardiac cases, with most cases being interventional. While trainees demonstrated competency in simple procedures (diagnostic cases, simple ASD closure), complex interventions (such as patent ductus arteriosus closure in premature infants) require ongoing mentorship for graduates. PDs recommended a minimum case volume of 400 total cases for trainees, including 250 interventional cases. In addition to case volumes, assessing trainee competency was deemed important, with clinical reasoning, judgment, skillset, teamwork, and complication management being key areas of evaluation. The study highlights the variability in congenital interventional cardiology training and the need for ongoing mentorship during the early career years. External mentorship programs, facilitated by national and international societies, are proposed to provide critical support for early career interventionalists thus enhancing patient care for congenital heart disease. Ultimately, the findings of this survey may serve as a framework for future training standards and guidelines in this specialized field.

[Methodological Study of Reliability Test of Percutaneous Ventricular Assist Device].

Prior to clinical application, reliability of percutaneous ventricular assist devices(pVAD) requires to be tested systematically. Currently, there's a lack of dedicated reliability testing equipment and methodologies for pVAD. Considering the structural and functional aspects of percutaneous ventricular assist devices, this study conducts research on pVAD reliability test engineering. Test setups, clinical conditions, failure modes, effects analysis, and evaluation models have been investigated. A highly feasible methodological approach for percutaneous ventricular assist device reliability assessment has been formed. This study offers valuable insights into standardizing their reliability evaluation in clinical settings.

Neuroblastoma Suppressor of Tumorigenicity 1 Mediates Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension Related to Congenital Heart Disease.

Endothelial-to-mesenchymal transition (EndMT) plays a critical role in the flow-induced vascular remodeling process, such as pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD). NBL1 (neuroblastoma suppressor of tumorigenicity 1) is a secreted glycoprotein that has been implicated in CHD-PAH by aggravating the phenotypic transformation of smooth muscle cells. However, the underlying mechanisms regarding the interplay between NBL1 and endothelial cells in CHD-PAH remain to be fully elucidated. Thus, we aimed to identify the potential effect of NBL1 on EndMT using a novel flow-associated PAH model with Nbl1 knockout rats. The phenotype of EndMT was detected using RNA sequencing and further examined using western blotting and immunostaining of pulmonary arteries. Our observations demonstrated that the novel strategy of Nbl1 knockout effectively attenuated flow-associated PAH through downregulation of EndMT to some extent. Mechanistic experiments were established on human pulmonary artery endothelial cells to confirm that EndMT was induced by NBL1 in vitro. After 7 days' stimulation with NBL1, concentrations of EndMT-related biomarkers and downstream transcription factors were quantified using RNA sequencing, western blotting, and immunocytochemistry. Both in vitro and in vivo experiments supported the imbalance of increased TGF-ß (transforming growth factor-ß) and dysregulation of BMP (bone morphogenetic protein) signaling by NBL1. Blocking the canonical TGF-ß pathway efficiently preserved endothelial function upon NBL1 stimulation. These data suggested that NBL1 aggravated flow-associated PAH by inducing EndMT via the TGF-ß and BMP signaling pathway. Thus, antagonizing NBL1 and rebalancing TGF-ß and BMP signaling may be a suitable therapeutic target for CHD-PAH.

Genetic deletion of CMG2 exacerbates systemic-to-pulmonary shunt-induced pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD-PAH) with systemic-to-pulmonary shunt (SPS) is characterized by proliferative vascular remodeling. Capillary morphogenesis gene-2 (CMG2) plays a key role in cell proliferation and apoptosis. This study aimed to determine the role of CMG2 in the pathogenesis of SPS-induced PAH. CMG2 levels were significantly downregulated in pulmonary arterioles from patients with Eisenmenger syndrome and rats with SPS-induced PAH. CMG2 was highly expressed in several cells including human pulmonary arterial smooth muscle cells (HPASMCs). CMG2-/- rats exhibited more severe PAH and pulmonary vascular remodeling than wild-type rats when exposed to SPS for 8 weeks. Overexpression of CMG2 significantly inhibited proliferation and promoted apoptosis of HPASMCs, while knockdown of CMG2 promoted cell proliferation and inhibited cell apoptosis. Next-generation sequencing and subsequent validation results suggested that PI3K-AKT was the most prominent signaling pathway regulated by differentially expressed genes (DEGs) in CMG2-/- rat lungs. Our work identified a novel role for CMG2 in SPS-induced PAH based on the findings that CMG2 deficiency exacerbates SPS-induced vascular remodeling in the development of PAH, indicating that CMG2 might act as a potential target for the treatment of CHD-PAH.

Initial experiences of transapical beating-heart mitral valve repair with a novel artificial chordal implantation device.

BACKGROUND: Severe mitral regurgitation (MR) is associated with progressive heart failure and impairment of survival. Degenerative MR accounts for most MV repair surgeries. Conventional mitral valve repair surgery requires cardiopulmonary bypass and is associated with significant morbidity and risks. Transapical beating-heart mitral valve repair by artificial chordae implantation with transesophageal echocardiography (TEE) guidance has the potential to significantly reduce surgical morbidity. We report the first-in-human experience of degenerative MR repair using a novel artificial chordae implantation device (MitralstitchTM system). METHODS: Ten patients with severe MR underwent transapical artificial chordae implantation using MitralstitchTM system. The procedure was performed through a small left thoracotomy under general anesthesia and TEE guidance. Patients underwent transthoracic echocardiography and other assessments during the follow-up. RESULTS: All 10 patients with an average age of 63.7 ± 9.6 years successfully received transapical artificial chordae implantation. Their MR reduced from severe to none or trace in five patients, mild in five patients before discharge. Five patients received one artificial chordal implantation, four patients received two, and one patient received three and edge-to-edge repair by locking two of them. The safety and efficacy endpoint were achieved in all patients at 1-month follow-up. At 1-year follow-up, six patients had mild MR, three patients had moderate MR, one patient had recurrence of severe MR and underwent surgical repair. CONCLUSIONS: The results of this first-in-human study show safety and feasibility of transapical mitral valve repair using MitralStitch system. Patient selection and technical refinement are crucial to improve the outcomes.

Bi-atrial or left atrial ablation of atrial fibrillation during concomitant cardiac surgery: A Bayesian network meta-analysis of randomized controlled trials.

OBJECTIVE: Surgical ablation of atrial fibrillation (AF) has become a routine procedure during concomitant cardiac surgery, however, the extension of lesion sets remain controversial. We sought to compare the relative benefit and risk of different lesion sets through a Bayesian network meta-analysis (NMA). METHODS: Pubmed, Embase, and Cochrane Trials databases were searched for randomized controlled trials (RCTs) comparing the rhythm outcome of AF patients undergoing pulmonary vein isolation (PVI), left atrial Maze (LAM), bi-atrial Maze (BAM), or no ablation during concomitant cardiac surgery. An NMA was conducted to explore the difference of over 1 year AF freedom as well as risks for early mortality and permanent pacemaker implantation (PPMI). RESULTS: A total of 2031 patients of 19 RCTs were included. PVI, LAM, and BAM (OR [95% Cr.I]: 5.02 [2.72, 10.02], 7.97 [4.93, 14.29], 8.29 [4.90, 14.86], p < .05) demonstrated higher freedom of AF compared with no ablation, however, no significant difference of rhythm outcome was found among the three ablation strategies based on the random-effects model. BAM was associated with an increase in early mortality when compared with no ablation (OR [95% Cr.I]: 4.08 [1.23, 17.30], p < .05), while none of the remaining comparisons reached statistical difference in terms of early mortality and PPMI. CONCLUSION: Bi-atrial ablation is not superior to left atrial ablation strategies in reducing AF recurrence for un-selected surgical patients. BAM has a higher risk of early mortality than no ablation, but no difference was found between bi-atrial and left atrial ablation in regard to early mortality and PPMI based on the current evidence.

Knockout of beta-2 microglobulin enhances cardiac repair by modulating exosome imprinting and inhibiting stem cell-induced immune rejection.

BACKGROUND AND AIMS: Allogeneic human umbilical mesenchymal stem cells (alloUMSC) are convenient cell source for stem cell-based therapy. However, immune rejection is a major obstacle for clinical application of alloUMSC for cardiac repair after myocardial infarction (MI). The immune rejection is due to the presence of human leukocyte antigen (HLA) class I molecule which is increased during MI. The aim of this study was to knockout HLA light chain ß2-microglobulin (B2M) in UMSC to enhance stem cell engraftment and survival after transplantation. METHODS AND RESULTS: We developed an innovative strategy using CRISPR/Cas9 to generate UMSC with B2M deletion (B2M-UMSC). AlloUMSC injection induced CD8+ T cell-mediated immune rejection in immune competent rats, whereas no CD8+ T cell-mediated killing against B2M-UMSC was observed even when the cells were treated with IFN-γ. Moreover, we demonstrate that UMSC-derived exosomes can inhibit cardiac fibrosis and restore cardiac function, and exosomes derived from B2M-UMSC are more efficient than those derived from UMSC, indicating that the beneficial effect of exosomes can be enhanced by modulating exosome's imprinting. Mechanistically, microRNA sequencing identifies miR-24 as a major component of the exosomes from B2M-UMSCs. Bioinformatics analysis identifies Bim as a putative target of miR-24. Loss-of-function studies at the cellular level and gain-of-function approaches in exosomes show that the beneficial effects of B2M-UMSCs are mediated by the exosome/miR-24/Bim pathway. CONCLUSION: Our findings demonstrate that modulation of exosome's imprinting via B2M knockout is an efficient strategy to prevent the immune rejection of alloUMSCs. This study paved the way to the development of new strategies for tissue repair and regeneration without the need for HLA matching.

Knockout of beta-2 microglobulin reduces stem cell-induced immune rejection and enhances ischaemic hindlimb repair via exosome/miR-24/Bim pathway.

Generating universal human umbilical mesenchymal stem cells (UMSCs) without immune rejection is desirable for clinical application. Here we developed an innovative strategy using CRISPR/Cas9 to generate B2M- UMSCs in which human leucocyte antigen (HLA) light chain ß2-microglobulin (B2M) was deleted. The therapeutic potential of B2M- UMSCs was examined in a mouse ischaemic hindlimb model. We show that B2M- UMSCs facilitated perfusion recovery and enhanced running capability, without inducing immune rejection. The beneficial effect was mediated by exosomes. Mechanistically, microRNA (miR) sequencing identified miR-24 as a major component of the exosomes originating from B2M- UMSCs. We identified Bim as a potential target of miR-24 through bioinformatics analysis, which was further confirmed by loss-of-function and gain-of-function approaches. Taken together, our data revealed that knockout of B2M is a convenient and efficient strategy to prevent UMSCs-induced immune rejection, and it provides a universal clinical-scale cell source for tissue repair and regeneration without the need for HLA matching in the future.

Transcatheter Closure of Patent Ductus Arteriosus under Echocardiography Guidance: A Randomized Controlled Noninferiority Trial.

BACKGROUND: Percutaneous occlusion under fluoroscopy guidance has become the preferred method for the treatment of patent ductus arteriosus (PDA). To avoid radiation exposure and contrast agent use, PDA occlusion under transthoracic echocardiography (TTE) guidance was conducted. OBJECTIVES: We assessed the hypothesis that the success rate of percutaneous PDA occlusion under TTE was noninferior to that under fluoroscopy guidance. METHODS: In this single-center trial, 100 patients were randomly assigned in a 1 : 1 ratio to the TTE group (n = 50) or to the fluoroscopy group (n = 50). The primary endpoint was the success rate of occlusion, with the noninferiority margin set at 8% for the between-group difference in intention-to-treat analysis. Secondary endpoints were hospitalization duration, cost, procedure time, and rate of adverse events including occluder migration, hemolysis, peripheral vascular complications, and residual shunt at 1-month and 12-month follow-up. RESULTS: Patient, defect, and device characteristics were similarly distributed between groups. The success rate of occlusion was 98% for the TTE group and 100% for the fluoroscopy group (absolute difference: -2%; 95% confidence interval: -5.9% to 1.9%). Cost and procedure duration were significantly lower in the TTE group, without adverse events in either group at a median of 12.0 months (range, 10.0-15.5 months) of follow-up. CONCLUSION: Percutaneous PDA occlusion can be performed via TTE guidance safely and effectively, and the success rate of the TTE-guided procedure was noninferior to that under fluoroscopy guidance, with reduced cost and procedure time. The trial is registered with http://www.chictr.org.cn (ChiCTR-ICR-15006334).

Personalized Three-Dimensional Printing and Echoguided Procedure Facilitate Single Device Closure for Multiple Atrial Septal Defects.

BACKGROUND: To evaluate the feasibility of using a single device to close multiple atrial septal defects (ASDs) under the guidance of transthoracic echocardiography (TTE) and with the aid of three-dimensional (3D) printing models. METHODS: Sixty-two patients with multiple ASDs were retrospectively analyzed. Thirty of these patients underwent TTE-guided closure (3D printing and TTE group) after a simulation of occlusion in 3D printing models. The remaining 32 patients underwent ASD closure under fluoroscopic guidance (conventional group). Closure status was assessed immediately and at 6 months after device closure. RESULTS: Successful transcatheter closure with a single device was achieved in 26 patients in the 3D printing and TTE group and 27 patients in the conventional group. Gender, age [18.8 ± 15.9 (3-51) years in the 3D printing and TTE group; 14.0 ± 11.6 (3-50) years in the conventional group], mean maximum distance between defects, prevalence of 3 atrial defects and large defect distance (defined as distance ≥7 mm), and occluder size used were similarly distributed between groups. However, the 3D printing and TTE group had lower frequency of occluder replacement (3.8% vs 59.3%, p < 0.0001), prevalence of mild residual shunts (defined as <5 mm) immediately (19.2% vs 44.4%, p < 0.05) and at 6 months (7.7% vs 29.6%, p < 0.05) after the procedure, and cost (32960.8 ± 2018.7 CNY vs 41019.9 ± 13758.2 CNY, p < 0.01). CONCLUSION: The combination of the 3D printing technology and ultrasound-guided interventional procedure provides a reliable new therapeutic approach for multiple ASDs, especially for challenging cases with large defect distance.

3D printing of implantable elastic PLCL copolymer scaffolds.

Poly(l-lactic acid) (PLLA) scaffolds have been used in regenerative medicine, however, they commonly suffer from low flexibility, restricting their application in the repair and reconstruction of soft tissues. In this study, poly(l-lactide-co-ε-caprolactone) (PLCL) copolymers were examined to modulate the elasticity of PLLA with the random presence of CL units in PLLA. Thermodynamic analysis revealed that the introduction of PCL could significantly decrease the melting point and glass transition temperature of PLLA, benefiting the extrusion and printing of PLCL. Diverse scaffolds with designed architectures including porous cubes with or without large holes, cambered plates with holes and round tubes could be easily constructed by 3D printing. In the process of elastic deformation, the maximum elastic stress of the copolymer scaffold was obviously increased from 19.6 to 31.5 MPa when the relative content of PCL was increased to 70%, while the elongation at break was evidently increased from 388% to about 1974%. The Young's modulus of PLCL was also significantly decreased (P < 0.05) in comparison with that of PLLA. PLCL scaffolds have good platelet and endotheliocyte adhesion ability and no obvious hemolysis was observed. In vivo subcutaneous implantation of PLCL scaffolds demonstrated superior biocompatibility. Collectively, this work highlights that copolymerization of PCL segments into PLLA is an effective approach to tune the 3D printability and the stiffness and elasticity of PLLA scaffolds. PLCL scaffolds hold great promise for the regeneration of soft tissues including but not limited to cartilage, myocardium, muscle, tendon and nervous tissues.

Three-dimensional printing assisted transcatheter closure of atrial septal defect with deficient posterior-inferior rim.

OBJECTIVE: Though successful transcatheter closure has been reported in secundum atrial septal defect (ASD) with deficient posterior-inferior rim, it is still difficult to screen the appropriate candidates. Three-dimensional printing (3DP) makes in vitro trial occlusion possible, and might provide a feasible method in the prediction of successful closure. METHODS: Thirty-five consecutive ASD patients (10M/25F, age, 47.7 ± 11.8 years) with deficient posterior-inferior rim (≤3 mm) were referred for attempted transcatheter closure, and personalized heart model (elastic rubber) was produced based on end-systolic MSCT images. The in vitro measurement and trial occlusion were performed for preoperative evaluation (in vitro successful/unsuccessful group), and the results were compared with postoperative outcomes. RESULTS: Successful in vitro occlusion was achieved in 30 patients (7M/23F), and the size of ASD was 27.1 ± 4.4 mm. The posterior-inferior rim was 0.95 ± 1.22 mm (rim defect in 17 patients), and 12 patients were associated with aortic rim deficiency. The subsequent transcatheter closure was performed successfully in 29 patients, and the occluder-diameter was identical to that of in vitro occlusion (35.0 ± 4.4 mm). The follow-up (1.4 ± 0.58 years) showed no residual shunt and related-complications. In unsuccessful in vitro group (n = 5), the range of rim deficiency was wider (P = 0.019) and the rim to inferior vena cava was shorter (4.60 ± 2.07 mm vs. 10.71 ± 5.28 mm, P = 0.016). Furthermore, transcatheter closure failed in all patients. CONCLUSIONS: In ASD with deficient posterior-inferior rim, 3DP allows accurate determination of the size and surrounding rims of ASD. Based on personalized heart model, in vitro trial occlusion is an effective method to identify the appropriate candidates for transcatheter closure.

A novel totally biodegradable device for effective atrial septal defect closure: A 2-year study in sheep.

OBJECTIVE: To evaluate the feasibility, efficacy, and safety of a fully biodegradable poly lactic acid (PLA)-based occluder for atrial septal defect (ASD) closure in an animal model. METHODS: ASDs, approximately 12-mm in diameter, were generated in sheep (n = 18) by needle puncture and balloon dilatation. For ASD closure, occluders were implanted by percutaneous transcatheter approach under echocardiographic guidance. Outcomes were evaluated by transthoracic echocardiography, electrocardiography, blood testing, and histology within the follow-up period ranging from 1 month to 2 years. RESULTS: All occluders were successfully implanted. During follow-up, no animal died; rectal temperatures, blood test results, and electrocardiograms were within normal ranges; and transthoracic echocardiograms, macroscopic studies, and histopathological and electron microscopic examination demonstrated that the occluders were well positioned, with no shifting, residual shunts, severe inflammation, thrombus formation, atrioventricular valve insufficiency, cardiac erosion or arrhythmias. The occluders gradually embedded into the endocardial tissue of the hosts with complete endothelialization and disk absorption at 12 months, and a distinct molecular weight decrease of the framework (to 9% of initial) at 24 months after implantation. CONCLUSIONS: In a sheep model, the use of totally biodegradable occluders appears feasible, efficacious and safe for ASD closure. Studies in humans are ongoing.

Feasibility and effectiveness of percutaneous balloon mitral valvuloplasty under echocardiographic guidance only.

OBJECTIVE: Percutaneous balloon mitral valvuloplasty (PBMV) is the treatment of choice in patients with isolated mitral stenosis. This study aimed to assess the feasibility of PBMV under echocardiography guidance only of isolated mitral stenosis (MS). METHODS: From October 2016 to Dec 2017, 20 consecutive patients with severe MS underwent PBMV with echocardiography as the only imaging modality at a single center. Outpatient follow-up including chest radiography, electrocardiography, and transthoracic echocardiography was conducted at 1, 3,6, and 12 months after the procedure. RESULTS: All 20 patients successfully underwent PBMV under echocardiography guidance without radiation and contrast agent. Among them, 2 patients were pregnant, 5 had chronic renal failure, and 1 had history of allergy to contrast. Mitral transvalvular pressure gradient measured at catheterization dropped from 13.35 ± 2.85 mm Hg to 5.10 ± 1.17 mm Hg (P < .01). Mitral valve area increased from 0.82 ± 0.10 cm2 pre-PBMV to 1.88 ± 0.24 cm2 post-PBMV (P < .01). Mean balloon diameter was 26.63 ± 0.93 mm. Mild mitral regurgitation developed in 6 patients. Mean follow-up duration was 6.27 ± 3.12 months. At last follow-up, mitral valve area remained high (1.71 ± 0.14 cm2 ) and mean transmitral pressure gradient low (6.07 ± 1.03 mm Hg). No pericardial effusion or peripheral vascular complications occurred. CONCLUSION: In this small experience, PBMV could be successfully performed under only echocardiography guidance and appeared safe and effective while avoiding radiation and contrast agent use.

The Molecular Mechanisms and Prevention Principles of Muscle Atrophy in Aging.

Muscle atrophy in aging is characterized by progressive loss of muscle mass and function. Muscle mass is determined by the balance of synthesis and degradation of protein, which are regulated by several signaling pathways such as ubiquitin-proteasome system, autophagy-lysosome systems, oxidative stress, proinflammatory cytokines, hormones, and so on. Sufficient nutrition can enhance protein synthesis, while exercise can improve the quality of life in the elderly. This chapter will discuss the epidemiology, pathogenesis, as well as the current treatment for aging-induced muscular atrophy.