Prevalence and Clustering of Cardiovascular Disease Risk Factors among Adults Along the Lancang-Mekong River: A Cross-Sectional Study from Low- and Middle-Income Countries.

Background: Progress in cardiovascular health is increasingly concentrated in high-income countries, while the burden of cardiovascular disease (CVD) is high in low- and middle-income countries, a clear health inequity that must be urgently addressed. Objective: This study aims to evaluate the prevalence and clustering of CVD risk factors in the three Lancang-Mekong regions. Methods: We conducted a population-based cross-sectional survey from January 2021 to March 2023 in China, Laos, and Cambodia. We compared the prevalence and clustering of CVD risk factors-including hypertension, dyslipidemia, diabetes mellitus, overweight/obesity, current smoking status, current drinking status, inadequate vegetable and fruit intake, and insufficient physical activity-across the three regions, further stratifying the data by gender and age. Multivariate logistic regression models were performed to explore factors influencing the aggregation of CVD risk factors (≥2, ≥3, ≥4). Results: A total of 11,005 adults were included in the study. Hypertension emerged as the primary metabolic risk factor in Laos (36.8%) and Cambodia (23.5%), whereas overweight/obesity was the primary risk factor in China (37.6%). In terms of behavioral risk factors, participants in all three regions showed insufficient vegetable and fruit intake. The prevalence of individuals without CVD risk factors was 10% in China, 1.9% in Laos, and 5.2% in Cambodia. Meanwhile, the prevalence of two or more risk factors was 64.6% in China, 79.2% in Laos, and 76.0% in Cambodia. Multivariate logistic regression models revealed that the propensity for CVD risk factors clustering was higher in men and increased with age in all three countries. Conclusions: CVD risk factors and multiple clustering are pressing health threats among adults in low- and middle-income areas along the Lancang-Mekong River Basin. This study highlights the urgent need for proactive tailored strategies to control CVD risk factors.

Biodegradable Cardiac Occluder with Surface Modification by Gelatin-Peptide Conjugate to Promote Endogenous Tissue Regeneration.

Transcatheter intervention has been the preferred treatment for congenital structural heart diseases by implanting occluders into the heart defect site through minimally invasive access. Biodegradable polymers provide a promising alternative for cardiovascular implants by conferring therapeutic function and eliminating long-term complications, but inducing in situ cardiac tissue regeneration remains a substantial clinical challenge. PGAG (polydioxanone/poly (l-lactic acid)-gelatin-A5G81) occluders are prepared by covalently conjugating biomolecules composed of gelatin and layer adhesive protein-derived peptides (A5G81) to the surface of polydioxanone and poly (l-lactic acid) fibers. The polymer microfiber-biomacromolecule-peptide frame with biophysical and biochemical cues could orchestrate the biomaterial-host cell interactions, by recruiting endogenous endothelial cells, promoting their adhesion and proliferation, and polarizing immune cells into anti-inflammatory phenotypes and augmenting the release of reparative cytokines. In a porcine atrial septal defect (ASD) model, PGAG occluders promote in situ tissue regeneration by accelerating surface endothelialization and regulating immune response, which mitigate inflammation and fibrosis formation, and facilitate the fusion of occluder with surrounding heart tissue. Collectively, this work highlights the modulation of cell-biomaterial interactions for tissue regeneration in cardiac defect models, ensuring endothelialization and extracellular matrix remodeling on polymeric scaffolds. Bioinspired cell-material interface offers a highly efficient and generalized approach for constructing bioactive coatings on medical devices.

Noncontact remote sensing of abnormal blood pressure using a deep neural network: a novel approach for hypertension screening.

Background: As the global burden of hypertension continues to increase, early diagnosis and treatment play an increasingly important role in improving the prognosis of patients. In this study, we developed and evaluated a method for predicting abnormally high blood pressure (HBP) from infrared (upper body) remote thermograms using a deep learning (DL) model. Methods: The data used in this cross-sectional study were drawn from a coronavirus disease 2019 (COVID-19) pilot cohort study comprising data from 252 volunteers recruited from 22 July to 4 September 2020. Original video files were cropped at 5 frame intervals to 3,800 frames per slice. Blood pressure (BP) information was measured using a Welch Allyn 71WT monitor prior to infrared imaging, and an abnormal increase in BP was defined as a systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg. The PanycNet DL model was developed using a deep neural network to predict abnormal BP based on infrared thermograms. Results: A total of 252 participants were included, of which 62.70% were male and 37.30% were female. The rate of abnormally high HBP was 29.20% of the total number. In the validation group (upper body), precision, recall, and area under the receiver operating characteristic curve (AUC) values were 0.930, 0.930, and 0.983 [95% confidence interval (CI): 0.904-1.000], respectively, and the head showed the strongest predictive ability with an AUC of 0.868 (95% CI: 0.603-0.994). Conclusions: This is the first technique that can perform screening for hypertension without contact using existing equipment and data. It is anticipated that this technique will be suitable for mass screening of the population for abnormal BP in public places and home BP monitoring.

Global, regional, and national burdens of atrial fibrillation/flutter from 1990 to 2019: An age-period-cohort analysis using the Global Burden of Disease 2019 study.

Background: Atrial fibrillation/flutter (AF/AFL) significantly impacts countries with varying income levels. We aimed to present worldwide estimates of its burden from 1990 to 2019 using data from the Global Burden of Disease (GBD) study. Methods: We derived cause-specific AF/AFL mortality and disability-adjusted life-year (DALY) estimates from the GBD 2019 study data. We used an age-period-cohort (APC) model to predict annual changes in mortality (net drifts), annual percentage changes from 50-55 to 90-95 years (local drifts), and period and cohort relative risks (period and cohort effects) between 1990 and 2019 by sex and sociodemographic index (SDI) quintiles. This allowed us to determine the impacts of age, period, and cohort on mortality and DALY trends and the inequities and treatment gaps in AF/AFL management. Results: Based on GBD data, our estimates showed that 59.7 million cases of AF/AFL occurred worldwide in 2019, while the number of AF/AFL deaths rose from 117 000 to 315 000 (61.5% women). All-age mortality and DALYs increased considerably from 1990 to 2019, and there was an increase in age risk and a shift in death and DALYs toward the older (>80) population. Although the global net drift mortality of AF/AFL decreased overall (-0.16%; 95% confidence interval (CI) = -0.20, 0.12 per year), we observed an opposite trend in the low-middle SDI (0.53%; 95% CI = 0.44, 0.63) and low SDI regions (0.32%; 95% CI = 0.18, 0.45). Compared with net drift among men (-0.08%; 95% CI = -0.14, -0.02), women had a greater downward trend or smaller upward trend of AF/AFL (-0.21%; 95% CI = -0.26, -0.16) in mortality in middle- and low-middle-SDI countries (P < 0.001). Uzbekistan had the largest net drift of mortality (4.21%; 95% CI = 3.51, 4.9) and DALYs (2.16%; 95% CI = 2.05, 2.27) among all countries. High body mass index, high blood pressure, smoking, and alcohol consumption were more prevalent in developed countries; nevertheless, lead exposure was more prominent in developing countries and regions. Conclusions: The burden of AF/AFL in 2019 and its temporal evolution from 1990 to 2019 differed significantly across SDI quintiles, sexes, geographic locations, and countries, necessitating the prioritisation of health policies based on risk-differentiated, cost-effective AF/AFL management.

Feasibility and safety of a percutaneous and non-fluoroscopic procedure for left atrial appendage closure in patients for whom fluoroscopy presents risk: a cohort study.

Background: Most patients undergoing left atrial appendage closure (LAAC) are older adult individuals with atrial fibrillation (AF) and many comorbidities, which may elevate the risk for complications associated with contrast agents with the fluoroscopic image-guided procedure. This retrospective cohort study of patients with AF at high risk for use of contrast agents compared the feasibility and safety of LAAC using percutaneous and non-fluoroscopic procedure with transesophageal echocardiography (TEE) as the only image guidance relative to those under fluoroscopic image guidance. Methods: In this retrospective study, we enrolled 126 patients with AF who underwent LAAC from September 2017 to December 2020. Patients were divided into 2 groups based on the imaging guidance modality: a TEE group (n=32) and a fluoroscopic group (n=94). We analyzed the differences in complete closure rates and device- and procedure-related complications between the 2 groups. Continuous variables were assessed using the Student t-test or Mann-Whitney test, while categorical variables were evaluated using Pearson chi-squared test or Fisher exact test. Propensity-score matching was used to adjust for baseline differences. Results: Propensity-score matching yielded 25 pairs of patients with similarly distributed age (72.9±6.9 vs. 73.1±4.9 years; P=0.925), gender (10:15 vs. 11:14; P>0.99), weight (68.3±11.2 vs. 68.1±12.3 kg; P=0.948), and alanine aminotransferase level (20.0±9.8 vs. 22.5±14.2 U/L; P=0.482). The LAA was successfully occluded in all patients, and the TEE group showed similar results to the fluoroscopic group in terms of success rate (100% vs. 100%; P>0.99) and hospitalization duration [5.0 (IQ1-IQ3: 3.0-7.0) vs. 5.0 (IQ1-IQ3: 3.0-6.0) days; P=0.498]. The groups also demonstrated comparable complication rates, with 1 (4.2%) case of pericardial effusion and 1 (4.2%) case of residual shunt in the TEE group, and 5 (20%) cases of residual shunt, 1 (4.2%) case of pericardial effusion, 1 (4.2%) case of myocardial infarction, and 1 (4.2%) case of access-related complications in the fluoroscopic group. There were no deaths. The overall incidence rate of procedure-related complications (6.2% vs. 18.1%, P=0.153) at mean 22.2±4.5 months follow-up between the 2 groups was similar. Conclusions: In patients with AF of high risk for use of contrast agents, LAAC under non-fluoroscopic guidance appears feasible and safe with similar outcomes to that under fluoroscopic guidance.

In vitro bench testing using patient-specific 3D models for percutaneous pulmonary valve implantation with Venus P-valve.

BACKGROUND: Due to the wide variety of morphology, size, and dynamics, selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation (PPVI). This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional (3D)-printed models for planning PPVI with the Venus P-valve. METHODS: Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University. RESULTS: 3D model bench testing altered treatment strategy in all patients (100%). One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly. In the remaining 14 patients, valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery. In four patients, it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract (RVOT) (n = 2) or risk of compression coronary artery (n = 2). Concerning sizing, we found that an oversize of 2-5 mm suffices. Anchoring of the valve was dictated by the flaring of the in- and outflow portion in the pulmonary artery. PPVI was successful in all 14 patients (absence of valve migration, no coronary compression, and none-to-mild residual pulmonary regurgitation [PR]). The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group (36 [2] vs. 32 [4], Z = -3.77, P <0.001). CONCLUSIONS: In vitro testing indicated no need to oversize the Venus P-valve to the degree recommended by the balloon-sizing technique, as 2-5 mm sufficed.

Development of an Expert-Level Right Ventricular Abnormality Detection Algorithm Based on Deep Learning.

PURPOSE: Studies relating to the right ventricle (RV) are inadequate, and specific diagnostic algorithms still need to be improved. This essay is designed to make exploration and verification on an algorithm of deep learning based on imaging and clinical data to detect RV abnormalities. METHODS: The Automated Cardiac Diagnosis Challenge dataset includes 20 subjects with RV abnormalities (an RV cavity volume which is higher than 110 mL/m2 or RV ejection fraction which is lower than 40%) and 20 normal subjects who suffered from both cardiac MRI. The subjects were separated into training and validation sets in a ratio of 7:3 and were modeled by utilizing a nerve net of deep-learning and six machine-learning algorithms. Eight MRI specialists from multiple centers independently determined whether each subject in the validation group had RV abnormalities. Model performance was evaluated based on the AUC, accuracy, recall, sensitivity and specificity. Furthermore, a preliminary assessment of patient disease risk was performed based on clinical information using a nomogram. RESULTS: The deep-learning neural network outperformed the other six machine-learning algorithms, with an AUC value of 1 (95% confidence interval: 1-1) on both training group and validation group. This algorithm surpassed most human experts (87.5%). In addition, the nomogram model could evaluate a population with a disease risk of 0.2-0.8. CONCLUSIONS: A deep-learning algorithm could effectively identify patients with RV abnormalities. This AI algorithm developed specifically for right ventricular abnormalities will improve the detection of right ventricular abnormalities at all levels of care units and facilitate the timely diagnosis and treatment of related diseases. In addition, this study is the first to validate the algorithm's ability to classify RV abnormalities by comparing it with human experts.

The first clinical data of the SAPIEN 3 aortic valve in the treatment of aortic stenosis in China.

Background: Data on outcomes following transcatheter aortic valve replacement with SAPIEN 3 in China is limited as it was approved by the National Medical Products since 2020. The present study was designed to collect clinical data on the SAPIEN 3 aortic valve in Chinese patients with bicuspid aortic valve and tricuspid aortic valve stenosis. Methods: We analyzed the patient characteristics, procedural features and procedural outcomes of the first 438 patients (223 for bicuspid aortic valve and 215 tricuspid aortic valve) from 21 provinces in 74 sites treated with the SAPIEN 3 valve system for transcatheter aortic valve replacement between September 2020 and May 2022. Results: Procedural mortality was 0.7%. 5 cases during the operation were converted to surgery. Among 438 cases, permanent pacemaker implantation was performed in a total of 12 cases (2.7%). The patient had severe leaflet calcification of the aortic valve, with moderate and severe calcification reaching 39.7% and 35.2% respectively. The size of the implanted valves was predominantly 26 mm and 23 mm, reaching 42.5% and 39.5% respectively. The incidence of moderate or severe perivalvular leak in the postoperative period was 0.5%, with a predominance of 90/10 and 80/20 valve deployment height. There was a significant difference in the deployment height of the valve between bicuspid aortic valve and tricuspid aortic valve, with the bicuspid aortic valve having a more deployment height of 90/10. Annulus size in bicuspid aortic valve group was significantly larger than tricuspid aortic valve group. Valve sizing for oversized, within size, and undersized were different between bicuspid aortic valve and tricuspid aortic valve. Conclusions: Procedural success rates were high, with similar and good results for bicuspid aortic valve and tricuspid aortic valve, low perivalvular leak for both valve types, and low permanent pacemaker implantation rates for both valve types. Annulus size, valve sizing and coronary artery height were significantly different in the BAV and TAV group.

Automated deep neural network-based identification, localization, and tracking of cardiac structures for ultrasound-guided interventional surgery.

Background: The increase in the use of ultrasound-guided interventional therapy for cardiovascular diseases has increased the importance of intraoperative real-time cardiac ultrasound image interpretation. We thus aimed to develop a deep learning-based model to accurately identify, localize, and track the critical cardiac structures and lesions (9 kinds in total) and to validate the algorithm's performance using independent data sets. Methods: This diagnostic study developed a deep learning-based model using data collected from Fuwai Hospital between January 2018 and June 2019. The model was validated with independent French and American data sets. In total, 17,114 cardiac structures and lesions were used to develop the algorithm. The model findings were compared with those of 15 specialized physicians in multiple centers. For external validation, 516,805 tags and 27,938 tags were used from 2 different data sets. Results: Regarding structure identification, the area under the receiver operating characteristic curve (AUC) of each structure in the training data set, optimal performance in the test data set, and median AUC of each structure identification were 1 (95% CI: 1-1), 1 (95% CI: 1-1), and 1 (95% CI: 1-1), respectively. Regarding structure localization, the optimal average accuracy was 0.83. As for structure identification, the accuracy of the model significantly outperformed the median performance of the experts (P<0.01). The optimal identification accuracies of the model in 2 independent external data sets were 89.5% and 90%, respectively (P=0.626). Conclusions: The model outperformed most human experts and was comparable to the optimal performance of all human experts in cardiac structure identification and localization, and could be used in the external data sets.

Evaluation of the effectiveness and safety of a multi-faceted computerized antimicrobial stewardship intervention in surgical settings: A single-centre cluster-randomized controlled trial.

BACKGROUND: Inappropriate antimicrobial use is common among patients undergoing surgery. It remains unclear whether a multi-faceted computerized antimicrobial stewardship programme is effective and safe in reducing inappropriate antimicrobial use in surgical settings. METHODS: A multi-faceted computerized antimicrobial stewardship intervention system was developed, and an open-label, cluster-randomized, controlled trial was conducted among 18 surgical teams that enrolled 2470 patients for open chest cardiovascular surgery. The surgical teams were divided at random into intervention and control groups at a ratio of 1:1. The primary endpoints were days of therapy (DOT)/1000 patient-days, defined daily dose (DDD)/1000 patient-days and length of therapy (LOT)/1000 patient-days. RESULTS: Mean DOT, DDD and LOT per 1000 patient-days were significantly lower in the intervention group compared with the control group (472.2 vs 539.8, 459.5 vs 553.8, and 438.4 vs 488.7; P<0.05), with reductions of 14.2% [95% confidence interval (CI) 11.8-16.7%], 18.7% (95% CI 15.9-21.4%) and 11.9% (95% CI 9.6-14.1%), respectively. The daily risk of inappropriate antimicrobial use after discharge from the intensive care unit decreased by 23.9% [95% CI 15.5-31.5% (incidence risk ratio 0.76, 95% CI 0.69-0.85)] in the intervention group. There was no significant difference in rates of infection or surgical-related complications between the groups. Median antimicrobial costs were significantly lower in the intervention group {873.4 [interquartile range (IQR) 684.5-1255.4] RMB vs 1178.7 (IQR 869.1-1814.5) RMB; P<0.001} (1 RMB approximately equivalent to 0.16 US$ in 2022). CONCLUSIONS: The multi-faceted computerized antimicrobial stewardship interventions reduced inappropriate antimicrobial use safely. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT04328090.

Ribosome biogenesis in disease: new players and therapeutic targets.

The ribosome is a multi-unit complex that translates mRNA into protein. Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation, differentiation, apoptosis, development, and transformation. The mTORC1, Myc, and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis. Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth. Myc is implicated in cancer development by enhancing RNA Pol II activity, leading to uncontrolled cancer cell growth. The deregulation of noncoding RNAs such as microRNAs, long noncoding RNAs, and circular RNAs is involved in developing blood, neurodegenerative diseases, and atherosclerosis. We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance. We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting, ribosome-stalling, and ribosome-collision. We summarize the role of ribosome biogenesis in the development of various diseases. Furthermore, we review the current clinical trials, prospective vaccines for COVID-19, and therapies targeting ribosome biogenesis in cancer, cardiovascular disease, aging, and neurodegenerative disease.

Long noncoding TSI attenuates aortic valve calcification by suppressing TGF-ß1-induced osteoblastic differentiation of valve interstitial cells.

INTRODUCTION: Calcific aortic valve disease (CAVD) is an active and cellular-driven fibrocalcific process characterised by differentiation of valve interstitial cells (VICs) towards an osteogenic-like phenotype. A recently identified lncRNA, lncTSI, has been reported to inhibit fibrogenesis through transforming growth factor (TGF)-ß/Smad3 pathway. Here, the present study aimed to investigate the role of lncTSI in CAVD. METHODS: The effect of TGF-ß1 on lncTSI of VICs was measured. TGF-ß1, RUNX2 and collagen I expression between calcified aortic valve tissue and normal samples by immunohistochemistry and western blotting. Human VICs were cultured and treated with TGF-ß1. SiRNA and pcDNA3.1-lncTSI plasmid transfection were used to silence and overexpress lncTSI in VICs for 48 h, Smads phosphorylation, RUNX2 and collagen I expression were then verified by western blotting. In ApoE-/- mice fed with 0.25 % high-cholesterol diet, AAV2-lncTSI were injected intravenously to observe their effect on the formation of aortic valve calcification. RESULTS: lncTSI was highly expressed in VICs treated with TGF-ß1. lncTSI was transcriptionally regulated by Smad3 and reversely inhibited TGF-ß1-induced Smad3 phosphorylation and downregulated profibrotic gene expression. Silencing lncTSI increased TGF-ß1-induced Smad3 phosphorylation, and subsequently, upregulated RUNX2 and collagen I expressions in VICs. While overexpression of lncTSI reversed the production of RUNX2 and collagen I in VICs. In a mouse CAVD model of 24 week 0.25 % high-cholesterol diet feeding, overexpression of lncTSI significantly reduced calcium deposition, RUNX2, pSmad3, and collagen I expression in aortic valve leaflets, with less aortic valve stenosis. CONCLUSIONS: The novel findings of present study suggested that lncTSI alleviated aortic valve calcification through negative regulation of the TGF-ß/Smad3 pathway. The results may help elucidate new diagnostic and therapeutic targets to prevent CAVD progression.

Bioinformatic analysis of potential biomarkers and mechanisms of immune infiltration in mitral regurgitation complicated by atrial fibrillation.

Background: Mitral regurgitation (MR) is one of the most prevalent valvular diseases. Degenerated MR-induced volume overload leads to left atrial enlargement and eventually, atrial fibrillation (AF). AF has a negative effect on patient prognosis despite recent advances in minimal invasive transcatheter devices for valve surgery. However, more effective strategies aimed at precisely treating from pathophysiology and genetic perspective are scarce. Methods: The gene expression datasets, GSE109744 and GSE79768, were obtained from the Gene Expression Omnibus database and analyzed to identify the differentially expressed genes (DEGs) in patients with mitral value prolapse (MVP) and AF. Subsequently, we predicted the extensive miRNA targets, and the protein-protein interaction (PPI) and miRNA-target gene regulatory networks were established. Functional enrichment analyses were performed for the DEGs. In addition, the co-expressed DEGs coupled with their predicted miRNAs and disease phenotypes involved in MVP and AF were assessed. Finally, the immune infiltration in both datasets was examined. Results: A total of 491 and 180 DEGs were identified in the mitral valve and left atrial specimens, respectively. From these, 11 integrated co-expressed DEGs were identified, namely, PRG4, GPR34, RELN, CA3, IL1B, EPHA3, CHGB, TCEAL2, B3GALT2, ASB11, and CRISPLD1. The enriched Gene Ontology terms and KEGG pathways associated with the DEGs were determined, and the top 10 hub genes and top 3 gene clusters were selected from the PPI network. A prediction of target miRNAs was performed based on the co-expressed DEGs. The enrichment of the co-expressed DEGs suggested that immune and inflammatory responses might be involved in the disease development through multiple immune related pathways, including the interaction of cytokines and chemokines. Notably, this result was consistent with the immune infiltration analysis since the proportions of naïve B cells and memory B cells were significantly different in MVP and AF tissues compared to normal tissues. Conclusions: MR and AF are related, and 11 co-expressed DEGs were found to be significantly associated with MVP with AF, and indeed, these may represent novel biomarkers. Several immune cells were found to contribute to the process of MVP and AF via diverse mechanisms, in particular, antigen-presenting cells.

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.

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.

Prevalence of Dyslipidemia and Availability of Lipid-Lowering Medications Among Primary Health Care Settings in China.

Importance: Dyslipidemia, the prevalence of which historically has been low in China, is emerging as the second leading yet often unaddressed factor associated with the risk of cardiovascular diseases. However, recent national data on the prevalence, treatment, and control of dyslipidemia are lacking. Objective: To assess the prevalence, treatment, and control of dyslipidemia in community residents and the availability of lipid-lowering medications in primary care institutions in China. Design, Setting, and Participants: This cross-sectional study used data from the China-PEACE (Patient-Centered Evaluative Assessment of Cardiac Events) Million Persons Project, which enrolled 2 660 666 community residents aged 35 to 75 years from all 31 provinces in China between December 2014 and May 2019, and the China-PEACE primary health care survey of 3041 primary care institutions. Data analysis was performed from June 2019 to March 2021. Exposures: Study period. Main Outcomes and Measures: The main outcome was the prevalence of dyslipidemia, which was defined as total cholesterol greater than or equal to 240 mg/dL, low-density lipoprotein cholesterol (LDL-C) greater than or equal to 160 mg/dL, high-density lipoprotein cholesterol (HDL-C) less than 40 mg/dL, triglycerides greater than or equal to 200 mg/dL, or self-reported use of lipid-lowering medications, in accordance with the 2016 Chinese Adult Dyslipidemia Prevention Guideline. Results: This study included 2 314 538 participants with lipid measurements (1 389 322 women [60.0%]; mean [SD] age, 55.8 [9.8] years). Among them, 781 865 participants (33.8%) had dyslipidemia. Of 71 785 participants (3.2%) who had established atherosclerotic cardiovascular disease (ASCVD) and were recommended by guidelines for lipid-lowering medications regardless of LDL-C levels, 10 120 (14.1%) were treated. The overall control rate of LDL-C (≤70 mg/dL) among adults with established ASCVD was 26.6% (19 087 participants), with the control rate being 44.8% (4535 participants) among those who were treated and 23.6% (14 552 participants) among those not treated. Of 236 579 participants (10.2%) with high risk of ASCVD, 101 474 (42.9%) achieved LDL-C less than or equal to 100 mg/dL. Among participants with established ASCVD, advanced age (age 65-75 years, odds ratio [OR], 0.63; 95% CI, 0.56-0.70), female sex (OR, 0.56; 95% CI, 0.53-0.58), lower income (reference category), smoking (OR, 0.89; 95% CI, 0.85-0.94), alcohol consumption (OR, 0.87; 95% CI, 0.83-0.92), and not having diabetes (reference category) were associated with lower control of LDL-C. Among participants with high risk of ASCVD, younger age (reference category) and female sex (OR, 0.58; 95% CI, 0.56-0.59) were associated with lower control of LDL-C. Of 3041 primary care institutions surveyed, 1512 (49.7%) stocked statin and 584 (19.2%) stocked nonstatin lipid-lowering drugs. Village clinics in rural areas had the lowest statin availability. Conclusions and Relevance: These findings suggest that dyslipidemia has become a major public health problem in China and is often inadequately treated and uncontrolled. Statins were available in less than one-half of the primary care institutions. Strategies aimed at detection, prevention, and treatment are needed.

Undifferentiated Chordae Tendineae of the Mitral Valve: Large Cohort Study of a Rare Mitral Malformation.

Aims: This study aimed to investigate the pathology, classification, diagnosis, and surgical prognosis of UCMV. Methods and Results: Consecutive paediatric patients with ≥ moderate-severe mitral regurgitation (MR) and mitral stenosis (MS) were recruited between October 2016 and July 2020. UCMV was diagnosed and classified into three grades according to the involvement of chorda groups and MS presence or absence; other mitral lesions were included as controls. Of 207 eligible patients, 75 with UCMV (10.0 m [interquartile range (IQR): 6.0-21.5]) and 110 with other mitral lesions (16.0 m [IQR: 5.0-43.5]) were diagnosed using echocardiography and surgical exploration. The associated chorda groups of UCMV were confirmed to show high agreement between echocardiography and surgery (kappa = 0.857, p < 0.001). At baseline surgery assessment, the UCMV group exhibited worse New York Heart Association functional class, more severe MR and MS grades, and fewer associated complex anomalies (all, p < 0.05) than the control group. After a mean follow-up of 8.3 (IQR:2.7-14.4) months and adjustment for covariates, the UCMV group required longer cardiopulmonary bypass and aortic clamp times, but there were no differences in the incidence of adverse events (p = 0.584). Class III was associated with higher risk of adverse events than classes I and II (p = 0.002). Conclusions: The UCMV spectrum constitutes a primary pathogenesis of paediatric MV dysfunction, which can be optimally diagnosed using echocardiography. Classification based on mitral anatomy and dysfunction can predict the risk of postoperative adverse events.

Inflammasomes as therapeutic targets in human diseases.

Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals. Inflammasome multiprotein complexes are composed of three parts: a sensor protein, an adaptor, and pro-caspase-1. Activation of the inflammasome leads to the activation of caspase-1, which cleaves pro-inflammatory cytokines such as IL-1ß and IL-18, leading to pyroptosis. Effectors of the inflammasome not only provide protection against infectious pathogens, but also mediate control over sterile insults. Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases, cancer, and neurodegenerative disorders. Here, we review the role of the inflammasome as a double-edged sword in various diseases, and the outcomes can be either good or bad depending on the disease, as well as the genetic background. We highlight inflammasome memory and the two-shot activation process. We also propose the M- and N-type inflammation model, and discuss how the inflammasome pathway may be targeted for the development of novel therapy.

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.

Effects of blood oxygen saturation on pulmonary artery remodeling in an in vitro perfusion circuit model.

BACKGROUND: Patients with transposition of the great arteries are likely to survive surgery despite severe pulmonary artery hypertension. However, the underlying mechanisms remain largely unknown. The present study aimed to test the hypothesis that high blood oxygen saturation may protect the pulmonary artery from remodeling. METHODS: An in vitro pulmonary artery perfusion model was successfully performed by connecting rabbit pulmonary artery to a closed perfusion circuit. Twenty-five rabbits were divided randomly into 5 groups according to exposure conditions: Normal Control (NC) group (unperfused normal pulmonary artery), High Saturation (HS) group (oxygen saturation range: 90-100%), Medium Saturation (MS) group (oxygen saturation: 65-75%); Low Saturation (LS) group (oxygen saturation: 40-50%), and anti-hypoxia inducible factor-1α (anti-HIF-1α) group (oxygen saturation range: 40-50%, and LW6, which is a novel HIF-1α inhibitor; was added). By staining and optical microscopy examination, pathological morphology was analyzed, and the protein expression levels of HIF-1α, angiotensin-II (Ang-II), endothelin-1 (ET-1), Rho-associated protein kinase-1 (Rock-1), and matrix metallopeptidase-2 (MMP-2) were determined by Western blotting. RESULTS: The amounts of elastin, muscle, and collagen and the protein levels of ET-1, HIF-1α, Rock-1, and MMP-2, increased significantly with decreased oxygen saturation in the perfusion circuit. A significant improvement in pathological morphology was observed in the anti-HIF1α group. The expression of HIF-1α, ET-1, Ang-II, Rock-1, and MMP-2 in the anti-HIF1α group was also significantly lower than that in the LS group. CONCLUSIONS: In the closed perfusion model, high blood oxygen saturation alleviated pulmonary vascular structural remodeling. Similar beneficial effects were observed when inhibiting the HIF-1α protein, suggesting a key role for HIF-1α in pulmonary artery remodeling.