Transcatheter closure of atrial septal defects with absent aortic rim and the predictors of right atrial reverse remodelingTranscatheter closure of atrial septal defects with absent aortic rim and the predictors of right atrial reverse remodeling: 5 years experience in China.

【Abstract】 Aim: To investigate the safety of interventional therapy in patients with secondary atrial septal defect (atrial septal defect, ASD) with complete aortic rim deficiency and explore the predictors of right atrial non-reverse remodeling. METHODS: 1011 patients with ASD who underwent transcatheter closure in the Department of Cardiology, Zhongshan Hospital affiliated to Fudan University from June 2017 to June 2022 were enrolled in the study. They were divided into a complete aortic rim deficiency group and without absent aortic rim group. Furthermore, patients who had an enlarged right atrial in the absent aortic rim group were divided into two sub-groups according to whether their right atrial reversed remodeling post-procedure. Multivariate logistic regression was used to determine the predictors of right atrial reversed remodeling. RESULTS: During the 1-year follow-up, no major operative complications occurred in all patients with the absence of an aortic rim and a normal edge. After the operation, the right heart remodeling was significantly reversed, multivariate logistic regression analysis was performed and found that preoperative without coronary heart disease, lower plasma creatinine level, and larger RA and RV dimension were predictive factors for the reverse of right atrial remodeling after treatment. CONCLUSION: Transcatheter closure of ASD with complete aortic rim deficiency is safe and feasible. The patients without coronary heart disease, the lower the creatinine value and the less tricuspid regurgitation before an operation, the more improvement of right atrial remodeling after the operation.

Home-based mobile-guided exercise-based cardiac rehabilitation among patients undergoing transcatheter aortic valve replacement (REHAB-TAVR): protocol for a randomised clinical trial.

INTRODUCTION: Transcatheter aortic valve replacement (TAVR) is a standard treatment for aortic stenosis, particularly in older adults. Reduced exercise capacity and frailty significantly impact outcomes in TAVR patients, yet current management lacks strategies to address these issues. This study aims to assess the effectiveness of home-based mobile-guided exercise-based cardiac rehabilitation in TAVR patients, led by a multidisciplinary team with clear progression milestones. METHODS AND ANALYSIS: The study involves 90 patients aged 60-89 in a single centre who will be randomised to a 3-month novel multidomain exercise intervention or routine care. Outcome assessors will be blinded towards group allocation. The primary outcome is the 6-min walk distance at month 3. The secondary outcomes include the 6-min walk distance at month 6, physical function measured by total Short Physical Performance Battery score and exercise adherence measured by the Exercise Adherence Rating Scale at months 3 and 6. Additional outcome measures, including rehospitalisations, death, handgrip strength, frailty (Fried Criteria and Essential Toolset), cognitive function (Mini-Mental State Examination), quality of life (EuroQol 5-Dimension 5-Level), nutritional status (Mini-Nutritional Assessment), anxiety (General Anxiety Disorder-7), depression (Geriatric Depression Scale), sleep (Pittsburgh Sleep Quality Index), functional capacity (Duke Activity Status Index), clinical indices (body mass index, symptoms, signs, left ventricular ejection fraction (LVEF), N-Terminal Pro-Brain Natriuretic Peptide, etc) and social support (Lubben Social Network Scale-6), along with comprehensive cost analysis, enhance the study's significance. The study's findings hold crucial implications for crafting an effective exercise-focused cardiac rehabilitation strategy for TAVR patients. Community implementation not only deepens understanding but also fosters the potential integration of exercise-based cardiac rehabilitation into self-care, promising enhanced patient adherence and overall cardiovascular health management. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Zhongshan Hospital, Fudan University Ethics Committee (B2022-062R). Results will be disseminated to local stakeholders and the research community through publications and conferences. TRIAL REGISTRATION NUMBER: NCT05989594.

Prevalence, factors and early outcomes of frailty among hospitalized older patients with valvular heart disease: A prospective observational cohort study.

AIM: The aim was to investigate the prevalence of, and factors related to frailty, together with early clinical outcomes, in hospitalized older patients with valvular heart disease (VHD) in China. DESIGN: A prospective observational cohort study was conducted. METHODS: A validated prospective survey was conducted to assess the prevalence of frailty, factors associated with it, and early clinical outcomes in hospitalized older patients with VHD, utilizing Fried's criterion. A total of 207 consecutive participants aged 65 years and older who underwent cardiac surgery were included in the study, spanning from September 2021 to December 2021. RESULTS: Frailty was detected in 78 patients (37.7%). Patients with multimorbidity, a New York Heart Association (NYHA) class of III/IV, or masticatory dysfunction had a greater incidence of frailty (p < 0.05). Patients with a normal albumin level and a higher frequency of exercise had a lower incidence of frailty (p < 0.05). Patients with frailty had longer hospital and intensive care unit stays and greater hospitalization costs than did those without frailty (p < 0.05). The 30-day adverse event rate of the frail group was also greater (11.5% vs. 3.1%). Therefore, early screening for conditions such as multimorbidity, cardiac dysfunction, and hypoalbuminemia is urgently needed to effectively address frailty, as it has been linked to unfavourable early outcomes. Moreover, promoting exercise and improving masticatory function and nutrition are crucial for preventing and managing frailty in older patients with VHD.

Safety and efficacy of the DragonFly system for transcatheter valve repair of degenerative mitral regurgitation: one-year results of the DRAGONFLY-DMR trial.

BACKGROUND: Severe degenerative mitral regurgitation (DMR) can cause a poor prognosis if left untreated. For patients considered at prohibitive surgical risk, transcatheter edge-to-edge repair (TEER) has become an accepted alternative therapy. The DragonFly transcatheter valve repair system is an innovative evolution of the mitral TEER device family to treat DMR. AIMS: Herein we report on the DRAGONFLY-DMR trial (ClinicalTrials.gov: NCT04734756), which was a prospective, single-arm, multicentre study on the safety and effectiveness of the DragonFly system. METHODS: A total of 120 eligible patients with prohibitive surgical risk and DMR ≥3+ were screened by a central eligibility committee for enrolment. The study utilised an independent echocardiography core laboratory and clinical event committee. The primary endpoint was the clinical success rate, which measured freedom from all-cause mortality, mitral valve reintervention, and mitral regurgitation (MR) >2+ at 1-year follow-up. RESULTS: At 1 year, the trial successfully achieved its prespecified primary efficacy endpoint, with a clinical success rate of 87.5% (95% confidence interval: 80.1-92.3%). The rates of major adverse events, all-cause mortality, mitral valve reintervention, and heart failure hospitalisation were 9.0%, 5.0%, 0.8%, and 3.4%, respectively. MR ≤2+ was 90.4% at 1 month and 92.0% at 1 year. Over time, left ventricular reverse remodelling was observed (p<0.05), along with significant improvements in the patients' functional and quality-of-life outcomes, shown by an increase in the New York Heart Association Class I/II from 32.4% at baseline to 93.6% at 12 months (p<0.001) and increased Kansas City Cardiomyopathy Questionnaire (KCCQ) score of 31.1±18.2 from baseline to 12 months (p<0.001). CONCLUSIONS: The DRAGONFLY-DMR trial contributes to increasing evidence supporting the safety and efficacy of TEER therapy, specifically the DragonFly system, for treating patients with chronic symptomatic DMR 3+ to 4+ at prohibitive surgical risk.

2024 Statement from Asia expert operators on transcatheter pulmonary valve replacement.

Transcatheter pulmonary valve replacement (TPVR), also known as percutaneous pulmonary valve implantation, refers to a minimally invasive technique that replaces the pulmonary valve by delivering an artificial pulmonary prosthesis through a catheter into the diseased pulmonary valve under the guidance of X-ray and/or echocardiogram while the heart is still beating not arrested. In recent years, TPVR has achieved remarkable progress in device development, evidence-based medicine proof and clinical experience. To update the knowledge of TPVR in a timely fashion, and according to the latest research and further facilitate the standardized and healthy development of TPVR in Asia, we have updated this consensus statement. After systematical review of the relevant literature with an in-depth analysis of eight main issues, we finally established eight core viewpoints, including indication recommendation, device selection, perioperative evaluation, procedure precautions, and prevention and treatment of complications.

Prognostic implications of pre-transcatheter aortic valve replacement computed tomography-derived coronary plaque characteristics and stenosis severity.

OBJECTIVES: The study aimed to investigate the prognostic value of pre-transcatheter aortic valve replacement (TAVR) computed tomography angiography (CTA) in assessing physiological stenosis severity (CTA-derived fractional flow reserve (CT-FFR)) and high-risk plaque characteristics (HRPC). MATERIALS AND METHODS: Among TAVR patients who underwent pre-procedure CTA, the presence and number of HRPCs (minimum lumen area of < 4 mm2, plaque burden ≥ 70%, low-attenuating plaques, positive remodeling, napkin-ring sign, or spotty calcification) as well as CT-FFR were assessed. The risk of vessel-oriented composite outcome (VOCO, a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) was compared according to the number of HRPC and CT-FFR categories. RESULTS: Four hundred and twenty-seven patients (68.4% were male) with 1072 vessels were included. Their mean age was 70.6 ± 10.6 years. Vessels with low CT-FFR (≤ 0.80) (41.7% vs. 15.8%, adjusted hazard ratio (HRadj) 1.96; 95% confidence interval (CI): 1.28-2.96; p = 0.001) or lesions with ≥ 3 HRPC (38.7% vs. 16.0%, HRadj 1.81; 95%CI 1.20-2.71; p = 0.005) demonstrated higher VOCO risk. In the CT-FFR (> 0.80) group, lesions with ≥ 3 HRPC showed a significantly higher risk of VOCO than those with < 3 HRPC (34.7% vs. 13.0%; HRadj 2.04; 95%CI 1.18-3.52; p = 0.011). However, this relative increase in risk was not observed in vessels with positive CT-FFR (≤ 0.80). CONCLUSIONS: In TAVR candidates, both CT-FFR and the presence of ≥ 3 HRPC were associated with an increased risk of adverse clinical events. However, the value of HRPC differed with the CT-FFR category, with more incremental predictability among vessels with negative CT-FFR but not among vessels with positive CT-FFR. CLINICAL RELEVANCE STATEMENT: In transcatheter aortic valve replacement (TAVR) candidates, pre-TAVR CTA provided the opportunity to assess coronary physiological stenosis severity and high-risk plaque characteristics, both of which are associated with worse clinical outcomes. KEY POINTS: • The current study investigated the prognostic value of coronary physiology significance and plaque characteristics in transcatheter aortic valve replacement patients. • The combination of coronary plaque vulnerability and physiological significance showed improved accuracy in predicting clinical outcomes in transcatheter aortic valve replacement patients. • Pre-transcatheter aortic valve replacement CT can be a one-stop-shop tool for coronary assessments in clinical practice.

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.

Mean compression ratio of a self-expandable valve is associated with the need for pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: The risk and timing of permanent pacemaker implantation (PPMI) after transcatheter aortic valve replacement (TAVR) is still hard to predict. We aimed to analyze the relationship between the compression ratio of a self-expandable valve (SEV) and the need for PPMI after TAVR. METHODS: A total of 106 patients who were implanted with the VitaFlow transcatheter aortic valve system and for whom complete imaging information was available were included in this retrospective cohort study. Eight lines perpendicular to the long axis of the SEV were drawn (the top and bottom of the SEV and the intersection of each row of wires) for measurement purposes. The compression ratio was calculated as 1 - (in vivo meridian/in vitro meridian) and compared between patients undergoing and those not undergoing PPMI after adjusting for implantation depth. Multivariable logistic regression and Cox proportional hazards models were used to assess factors associated with the risk and timing of the need for PPMI. RESULTS: Fifteen (14.2%) patients underwent PPMI after TAVR. Patients with a higher mean compression ratio (20%, odds ratio [OR] = 214.82; p < 0.001) and prior right bundle branch block (OR = 51.77; p = 0.015) had a higher risk of the need for PPMI after TAVR. These two factors were also associated with the timing of PPMI, according to the Cox proportional hazards model. CONCLUSIONS: The compression ratio of the SEV was positively associated with the risk of PPMI after TAVR, and the association was most significant in the annular and supravalvular planes. The compression ratio may also affect the time to PPMI.

Five-year follow-up after percutaneous pulmonary valve implantation using the Venus P-valve system for patients with pulmonary regurgitation and an enlarged native right ventricular outflow tract.

BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) with the self-expandable Venus P-valve system is a promising treatment for patients with pulmonary regurgitation (PR) and a native right ventricular outflow tract (RVOT). However, limited data is available regarding its midterm outcomes. This study assessed the midterm clinical and echocardiographic outcomes following Venus P-valve implantation. METHODS: From 2013 to 2018, 55 patients with moderate or severe PR after surgical RVOT repair with a transannular or RVOT patch were consecutively enrolled from six hospitals in China. Five-year clinical and echocardiographic outcomes were collected and evaluated. The primary endpoint was a freedom from all-cause mortality and reintervention. RESULTS: At 5 years, the primary endpoint was met for 96% of patients, corresponding to a freedom from all-cause mortality of 96% (95% confidence interval [CI]: 86%-99%) and freedom from reintervention of 98% (95% CI: 87%-100%). Endocarditis was reported in five patients (four patients within 1 year and one patient at 5 years) following PPVI. Transpulmonary gradient and stent orifice diameter remained stable compared to at discharge (p＞0.05). No paravalvular leak was reported while only 1 patient gradually increased to moderate PR during follow-up. Significant improvement of RV diameter and LVEF (p＜0.001) sustained over the 5-year follow-up, in consistent with remarked improved New York Heart Association(NYHA) functional class (p＜0.001). CONCLUSION: The 5-year results of the China VenusP Study demonstrated the midterm benefits of Venus P-valve implantation in the management of patients with severe PR with an enlarged native RVOT by providing sustained symptomatic and hemodynamic improvement.

Diagnostic Value of Serum Galectin-3 Binding Protein Level in Patients with Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) still lacks effective biomarkers to assist in its diagnosis and prognosis. Galectin-3 binding protein (Gal-3BP) plays a role in immune and inflammatory diseases. OBJECTIVE: This study aimed to evaluate Gal-3BP as a prognostic and predictive factor in patients with PAH. METHODS: From January 2017 to December 2019, we enrolled 167 consecutive PAH patients and 58 healthy controls. Right heart catheterization (RHC) was used to diagnose PAH. Serum Gal-3BP levels were measured by high-sensitivity human enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum Gal-3BP levels in the PAH group were significantly higher compared with the control group (4.87±2.09 vs 2.22±0.86 µg/mL, p<0.001). Gal-3BP level was correlated with several hemodynamic parameters obtained from RHC (p<0.001). Multivariate linear regression analysis showed that Gal-3BP was a risk factor for PAH (odds ratio (OR)=2.947, 95% CI: 1.821-4.767, p<0.001). The optimal cut-off value of serum Gal-3BP level for predicting PAH was 2.89 µg/mL (area under the curve (AUC)=0.860, 95 % CI: 0.811-0.910, p<0.001). Kaplan-Meier analysis showed that Gal-3BP levels above the median (4.87 µg/mL) were associated with an increased risk of death in patients with PAH (hazard ratio (HR)=8.868, 95 % CI: 3.631-21.65, p<0.0001). Cox multivariate risk regression analysis showed that Gal-3BP was a risk factor for death in PAH patients (HR=2.779, 95 % CI: 1.823-4.237, p<0.001). CONCLUSION: Serum Gal-3BP levels were increased in patients with PAH, and levels of Gal-3BP were associated with the severity of PAH. Gal-3BP might have predictive value for the diagnosis and prognosis of PAH.

Early 6 months usage of single anTiplAtelet OR anTicoAgulant followed by single antiplatelet after transcatheter aortic valve replacement: protocol for a multicentre, open-label, randomised controlled clinical trial.

INTRODUCTION: The strategy for initiating antithrombotic therapy to prevent bioprosthetic valve thrombosis (BPVT) after transcatheter aortic valve replacement (TAVR) remains uncertain. There is still lacking evidence on the efficacy and safety of early 6 months usage of single-antiplatelet therapy (SAPT) or oral anticoagulant (OAC) after TAVR in patients without anticoagulant indications. METHODS AND ANALYSIS: This is a multicentre, randomised controlled, open-label trial, and 650 patients undergoing TAVR from 13 top TAVR centres in China will be recruited. Each eligible participant will be randomly assigned to two groups (1:1 ratio) as (1) SAPT (aspirin 75-100 mg for 6 months) group or (2) OAC group (warfarin, therapeutic international normalised ratio at 1.8-2.5 for 6 months), both followed by sequential aspirin 75-100 mg for 6 months. Participants in both groups will be invited for three follow-up visits of 1, 6 and 12 months after discharge. We will use both the net clinical benefit endpoint (composite of all-cause mortality, myocardial infarction, stroke/transient ischaemic attacks, peripheral artery thrombosis, intracardiac thrombosis and major bleeding and disabling or life-threatening bleeding) and the BPVT endpoint evaluated by four-dimensional CT as our primary endpoints. P value of <0.05 of two-sided test will be considered statistically significant. ETHICS AND DISSEMINATION: The present study was approved by the Institutional Review Boards at Fuwai Hospital, National Center for Cardiovascular Diseases of China (Approval No. 2023-1947). All patients will be informed of the details of the study and will sign an informed consent prior to inclusion in the study. Results of this study will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05375474.

Identification and Validation of Key Gene Modules and Pathways in Coronary Artery Disease Development and Progression.

The development and progression of atherosclerosis represent a chronic process involving complex molecular interactions. Therefore, identifying the potential hub genes and pathways contributing to coronary artery disease (CAD) development is essential for understanding its underlying molecular mechanisms. To this end, we performed transcriptome analysis of peripheral venous blood collected from 100 patients who were divided into four groups according to disease severity, including 27 patients in the atherosclerosis group, 22 patients in the stable angina group, 35 patients in the acute myocardial infarction group, and 16 controls. Weighted gene co-expression network analysis was performed using R programming. Significant module-trait correlations were identified according to module membership and genetic significance. Metascape was used for the functional enrichment of differentially expressed genes between groups, and the hub genes were identified via protein-protein interaction network analysis. The hub genes were further validated by analyzing Gene Expression Omnibus (GSE48060 and GSE141512) datasets. A total of 9,633 messenger ribonucleic acids were detected in three modules, among which the blue module was highly correlated with the Gensini score. The hub genes were significantly enriched in the myeloid leukocyte activation pathway, suggesting its important role in the progression of atherosclerosis. Among these genes, the Mediterranean fever gene (MEFV) may play a key role in the progression of atherosclerosis and CAD severity.

Preliminary Implantation of a Novel TAVR Device With Polymeric Leaflets for Symptomatic Calcific Aortic Disease.

The indication for transcatheter aortic valve replacement to younger patients remains controversial. Here, we report a successful implantation of the first polymeric transcatheter aortic valve replacement device in a patient with severe calcific aortic stenosis. Compared with conventional valves, the novel valve has better durability, larger orifice area, and better morphological adaptability. (Level of Difficulty: Intermediate.).

First-in-human study of the K-Clip™ transcatheter annular repair system for severe functional tricuspid regurgitation.

BACKGROUND: Severe TR is associated with impaired prognosis while limited interventional options available. The purpose of this observational first-in-human experience with the K-Clip™ transcatheter tricuspid annular reconstruction system is to investigate its feasibility, safety as well as short-term clinical impact on patients with severe functional tricuspid regurgitation (TR). METHODS: In this compassionate-use, prospective, multi-center, single-arm study, 15 patients with severe symptomatic functional TR were treated with the K-Clip™ system and followed up at 30 days after discharge. Feasibility endpoints consisted of safety (major clinical cardiovascular events (MACEs), echocardiographic, clinical and functional endpoints. RESULTS: All the 15 patients (9 males, 72.67 ± 9.42 years of age) successfully received implants and no MACEs were reported throughout the study at 30 days. Between baseline and 30 days, echocardiography showed remarkable reduction of tricuspid annular circumference and area by 14.30% and 25.96%. Improvement of ≥ + 2 grade and ≥ +3 grade TR was presented in 9/15(60.00%) and 4/15(26.67%) respectively while 10/15(66.67%) of patients had ≤ moderate TR. Clinical evaluation indicated that 86.67% of patients were finally in NYHA functional class I or II (p<0.001) and overall Kansas City Cardiomyopathy Questionnaire score improved from 62.28 ± 18.97 to 77.90 ± 11.70 (p = 0.016). CONCLUSION: Our first-in-human results of the transcatheter tricuspid annular reconstruction using the K-Clip™ system demonstrated initial favorable procedural success, acceptable safety and remarkable TR reduction in consistent with significant clinical improvement. Larger-scaled prospective trials with longer follow-up duration are warranted to further determine whether these promising findings could be promoted to a broader population in the long term.

A prediction model for permanent pacemaker implantation after transcatheter aortic valve replacement.

BACKGROUND: This study aims to develop a post-procedural risk prediction model for permanent pacemaker implantation (PPMI) in patients treated with transcatheter aortic valve replacement (TAVR). METHODS: 336 patients undergoing TAVR at a single institution were included for model derivation. For primary analysis, multivariate logistic regression model was used to evaluate predictors and a risk score system was devised based on the prediction model. For secondary analysis, a Cox proportion hazard model was performed to assess characteristics associated with the time from TAVR to PPMI. The model was validated internally via bootstrap and externally using an independent cohort. RESULTS: 48 (14.3%) patients in the derivation set had PPMI after TAVR. Prior right bundle branch block (RBBB, OR: 10.46; p < 0.001), pre-procedural aortic valve area (AVA, OR: 1.41; p = 0.004) and post- to pre-procedural AVA ratio (OR: 1.72; p = 0.043) were identified as independent predictors for PPMI. AUC was 0.7 and 0.71 in the derivation and external validation set. Prior RBBB (HR: 5.07; p < 0.001), pre-procedural AVA (HR: 1.33; p = 0.001), post-procedural AVA to prosthetic nominal area ratio (HR: 0.02; p = 0.039) and post- to pre-procedural troponin-T difference (HR: 1.72; p = 0.017) are independently associated with time to PPMI. CONCLUSIONS: The post-procedural prediction model achieved high discriminative power and accuracy for PPMI. The risk score system was constructed and validated, providing an accessible tool in clinical setting regarding the Chinese population.

Novel arm-width-expandable transcatheter edge-to-edge repair system: Preclinical experiment and first-in-human study.

BACKGROUND: The ValveClasp system is a novel transcatheter edge-to-edge repair (TEER) device with an arm-width-expandable clip that allows treatment of patients with only one clip more frequently. OBJECTIVES: This study aimed to evaluate the feasibility and safety of a novel TEER device in porcine models and patients. METHODS: Fourteen young adult pigs were enrolled. A clip with an expanded arm was implanted under epicardial echocardiography and fluoroscopy guidance. Five patients with at least moderate-to-severe mitral regurgitation underwent TEER using the ValveClasp system to test the safety and effectiveness of the device. RESULTS: The device success rate was 100% (14/14) in the animal experiments, and all clips were deployed at the A2P2 segments, forming a double-orifice mitral valve. Gross observations on day 180 showed a wide and continuous tissue bridge between the leaflets. The acute procedural success rate was 100% (5/5). Only one clip was required in all patients, and all achieved effective postoperative endpoints (grade ≤2+). During 30-day follow-up, no adverse events occurred. All patients' vena Contracta width (from 8.04 0.71 mm to 3.84 ± 1.18 mm, p = 0.012), mitral regurgitation area (from 12.75 ± 3.13 cm2 to 3.50 ± 1.66 cm2 , p = 0.008), and left ventricular end diastolic diameter (from 52.00 ± 2.92 mm to 46.00 ± 3.08 mm, p = 0.040) were considerably decreased, without obvious mitral stenosis. CONCLUSIONS: The novel arm-width-expandable ValveClasp device is safe for TEER for treating severe mitral regurgitation.

Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs.

Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular syndrome characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, which eventually leads to right heart failure and even death. Although the exact mechanism of PAH is not fully understood, pulmonary vasoconstriction, vascular remodeling, immune and inflammatory responses, and thrombosis are thought to be involved in the development and progression of PAH. In the era of non-targeted agents, PAH had a very dismal prognosis with a median survival time of only 2.8 years. With the deep understanding of the pathophysiological mechanism of PAH as well as advances in drug research, PAH-specific therapeutic drugs have developed rapidly in the past 30 years, but they primarily focus on the three classical signaling pathways, namely the endothelin pathway, nitric oxide pathway, and prostacyclin pathway. These drugs dramatically improved pulmonary hemodynamics, cardiac function, exercise tolerance, quality of life, and prognosis in PAH patients, but could only reduce pulmonary arterial pressure and right ventricular afterload to a limited extent. Current targeted agents delay the progression of PAH but cannot fundamentally reverse pulmonary vascular remodeling. Through unremitting efforts, new therapeutic drugs such as sotatercept have emerged, injecting new vitality into this field. This review comprehensively summarizes the general treatments for PAH, including inotropes and vasopressors, diuretics, anticoagulants, general vasodilators, and anemia management. Additionally, this review elaborates the pharmacological properties and recent research progress of twelve specific drugs targeting three classical signaling pathways, as well as dual-, sequential triple-, and initial triple-therapy strategies based on the aforementioned targeted agents. More crucially, the search for novel therapeutic targets for PAH has never stopped, with great progress in recent years, and this review outlines the potential PAH therapeutic agents currently in the exploratory stage to provide new directions for the treatment of PAH and improve the long-term prognosis of PAH patients.

Gut microbiome alterations in pulmonary hypertension in highlanders and lowlanders.

Background: Alterations in the gut microbiota have been observed in patients with pulmonary hypertension (PH), though whether the roles of the gut microbiota in PH at different altitudes are the same is unknown. This study aims to evaluate the associations of the gut microbiome with PH in highlanders and lowlanders. Methods: PH patients and controls were recruited from those who permanently live on the Tibetan plateau (highlanders) or the plains (lowlanders), and underwent transthoracic echocardiography close to their altitude of residence (at 5070 m for highlanders versus6 m for lowlanders). The gut microbiome was profiled using metagenomic shotgun sequencing. Results: In total, 13 PH patients (46% highlanders) and 88 controls (70% highlanders) were included. The overall microbial composition was different in PH patients compared to controls (p=0.003). Notably, among lowlanders, a composite microbial score of pro-atherosclerotic trimethylamine-producing species was increased in PH patients compared with that in controls (p=0.028), while among highlanders no such difference was observed (p=0.087). Another composite gut microbial score including eight species of Lactobacillus, which has shown beneficial effects on cardiovascular functions, was higher in highlanders than lowlanders (p<0.01). Furthermore, this score tended to be lower in PH patients than controls among highlanders (p=0.056) but not among lowlanders (p=0.840). In addition, the gut microbiome showed a good performance in distinguishing PH patients from controls in both lowlanders and highlanders. Conclusions: Our study reported differently altered gut microbiome profiles between highland and lowland PH patients, highlighting the distinct microbial mechanism in PH in highlanders compared with lowlanders.