Although the use of bioabsorbable occluder is expected to reduce the risk of metal occluder-related complications, it has not been approved due to incomplete degradation and new complications. Novel fully bioabsorbable occluders were designed to overcome such limitations. The aim of this study was to investigate the efficacy and safety of a fully biodegradable occluder in patients with ventricular septal defects. 125 patients with perimembranous ventricular septal defect (VSD) larger than 3 mm were screened from April 2019 to January 2020 in seven centers. 108 patients were enrolled and randomized into the bioabsorbable occluder group (n = 54 patients) and nitinol occluder group (n = 54). A non-inferiority design was utilized and all patients underwent transcatheter device occlusion. Outcomes were analyzed with a 24-month follow-up. All patients were successfully implanted and completed the trial. No residual shunt >2 mm was observed during follow-up. Transthoracic echocardiography showed a hyperechoic area corresponding to the bioabsorbable occluder which decreased primarily during the first year after implantation and disappeared within 24 months. Postprocedural arrhythmia was the only occluder-related complication with an incidence of 5.56% and 14.81% for the bioabsorbable and nitinol groups, respectively (P = 0.112). The incidence of sustained conduction block was lower in the bioabsorbable occluder group (0/54 vs. 6/54, P = 0.036) at 24-month follow-up. In conclusion, the novel fully bioabsorbable occluder can be successfully and safely implanted under echocardiography guidance and reduce the incidence of sustained postprocedural arrythmia. The efficacy and safety of this fully biodegradable occluder are non-inferior to that of a traditional nitinol one.

Piezo1 plays a key role in the immune response during sepsis. To date, our understanding of the role of Piezo1 in inflammatory diseases has mostly been limited to influencing vasomotor function and regulating inflammatory infiltration. Whether and how Piezo1 in macrophages is involved in developing septic cardiac dysfunction has never been explored. Here, we have successfully established a mouse model with myeloid cell-specific knockdown of Piezo1. The intraperitoneal injection of lipopolysaccharide (LPS) resulted in a significant increase in cardiac macrophage infiltration, as well as an increase in the expression of inflammatory factors and the inflammatory response. However, myeloid cell-specific knockdown of Piezo1 impaired this response, leading to an increase in macrophage polarization towards the M2 type and the decreased inflammatory response. As a result, myocardial injury caused by sepsis was attenuated. We have also demonstrated that the PI3K/AKT pathway is significantly activated after Piezo1 knockdown, resulting in reduced myocardial dysfunction. Our data indicate that myeloid cell-specific knockdown of Piezo1 can influence macrophage polarization and thus exert cardioprotective effects in a murine model of sepsis, providing potential ideas and targets for the treatment of infectious cardiac dysfunction.

Background The burden of valvular heart disease (VHD) is rising rapidly globally, accompanied by substantial geographical disparities. Although altitude may influence cardiovascular system, no community-based studies have yet explored altitudinal differences in VHD epidemiology. Objective This study aims to investigate the prevalence, spectrum and aetiology of VHD in different altitude areas. Methods We conducted two sequential community-based echocardiography screening programmes in Yunnan Province of China and included 5059 eligible participants aged 35 years and older. The multivariable Poisson regression models with robust variance were performed to assess the association of different altitude groups with VHD and its subtypes. Results The prevalence of overall VHD, clinically significant VHD and clinically significant regurgitant VHD was 36.7%, 2.5% and 2.4%, respectively. After stratification by altitude, the prevalence of any VHD among participants in the <2000 m, 2000–2499 m, 2500–2999 m and ≥3000 m groups was 30.4%, 40.9%, 35.0% and 44.3%, respectively. The fully adjusted models showed that the prevalence ratios for VHD in the 2000–2499 m, 2500–2999 m and ≥3000 m groups were 1.28 (95% CI 1.15 to 1.42), 1.20 (95% CI 1.02 to 1.41) and 1.34 (95% CI 1.04 to 1.72), compared with the <2000 m group. Clinically significant VHD in the <3000 m altitude group was predominantly degenerative in aetiology, whereas functionality was most prevalent in the ≥3000 m altitude group. Subgroup analysis identified some high-risk populations, including male, minority ethnicity, 60 years and older and high systolic blood pressure. Conclusions Adults living at high altitudes have a higher prevalence risk of VHD; significant altitudinal differences exist in the characteristics and aetiology of VHD. The findings could provide insights into primary prevention and early screening for VHD in low- and middle-income countries where a majority of the population lives at high altitudes.

Background: Coronary microvascular dysfunction (CMD) persists after percutaneous coronary intervention (PCI) in individuals with coronary artery disease (CAD). This study assessed CMD using combined dipyridamole‐exercise stress echocardiography (DExE) and myocardial strain/work to evaluate the impact on left ventricular (LV) function. Methods: This prospective study enrolled CAD individuals who underwent left anterior descending artery PCI and DExE assessment at 3 months post‐PCI to evaluate myocardial strain/work parameters at rest and stress. The primary endpoint was adverse clinical events, and the secondary endpoint was Seattle Angina Questionnaire (SAQ) health status at 1‐year. Results: The cohort comprised 84 individuals (54 ± 10 years, 17.9% female). Participants were stratified into two groups by coronary flow velocity reserve (CFVR): CFVR ≥ 2.5 group ( n = 63) and CFVR < 2.5 group ( n = 21). Compared with the CFVR ≥ 2.5 group, the CFVR < 2.5 group showed impaired LV functional reserve, with lower global longitudinal strain (GLS), global work index (GWI), and global work efficiency (GWE) at peak exercise and recovery, lower peak exercise global constructive work (GCW), higher recovery global wasted work (GWW), and smaller absolute changes ΔE—R (difference before vs. after exercise stress) in GLS, GWI, and GCW (all p < 0.05). In multivariable analysis, peak exercise GCW, recovery GWW, and ΔGCW (E − R) were independent predictors of CMD. At 1 year, no adverse clinical events occurred, and the CFVR ≥ 2.5 group had higher SAQ physical limitation (92.86 ± 11.38 vs. 82.14 ± 17.93), quality of life (95.63 ± 10.57 vs. 83.33 ± 19.90), and summary score (94.05 ± 8.51 vs. 85.71 ± 15.71) than the CFVR < 2.5 group (all p < 0.05). Conclusions: Combined DExE with myocardial strain/work analysis effectively evaluates LV function in CMD. Decreased CFVR post‐PCI is associated with impaired LV function and worse 1‐year quality of life outcomes, underscoring the need for close cardiac function monitoring in post‐PCI CMD individuals. Trial Registration: URL: https://www.chictr.org.cn/ ; Unique identifier: ChiCTR2500103229.

Background: The present study aimed to explore the correlation between calcium-activated potassium channels, left atrial flow field mechanics, valvular atrial fibrillation (VAF), and thrombosis. The process of transforming mechanical signals into biological signals has been revealed, which offers new insights into the study of VAF. Methods: Computational fluid dynamics simulations use numeric analysis and algorithms to compute flow parameters, including turbulent shear stress (TSS) and wall pressure in the left atrium (LA). Real-time PCR and western blotting were used to detect the mRNA and protein expression of IKCa2.3/3.1, ATK1, and P300 in the left atrial tissue of 90 patients. Results: In the valvular disease group, the TSS and wall ressure in the LA increased, the wall pressure increased in turn in all disease groups, mainly near the mitral valve and the posterior portion of the LA, the increase in TSS was the most significant in each group near the mitral valve, and the middle and lower part of the back of the LA and the mRNA expression and protein expression levels of IKCa2.3/3.1, AKT1, and P300 increased (p < 0.05) (n = 15). The present study was preliminarily conducted to elucidate whether there might be a certain correlation between IKCa2.3 and LA hemodynamic changes. Conclusions: The TSS and wall pressure changes in the LA are correlated with the upregulation of mRNA and protein expression of IKCa2.3/3.1, AKT1, and P300.

Background Ventricular septal defect (VSD) is the most common congenital heart disease. Although a small number of genes associated with VSD have been found, the genetic factors of VSD remain unclear. In this study, we evaluated the association of 10 candidate single nucleotide polymorphisms (SNPs) with isolated VSD in a population from Southwest China. Methods Based on the results of 34 congenital heart disease whole-exome sequencing and 1000 Genomes databases, 10 candidate SNPs were selected. A total of 618 samples were collected from the population of Southwest China, including 285 VSD samples and 333 normal samples. Ten SNPs in the case group and the control group were identified by SNaPshot genotyping. The chi-square (chi(2)) test was used to evaluate the relationship between VSD and each candidate SNP. The SNPs that had significant P value in the initial stage were further analysed using linkage disequilibrium, and haplotypes were assessed in 34 congenital heart disease whole-exome sequencing samples using Haploview software. The bins of SNPs that were in very strong linkage disequilibrium were further used to predict haplotypes by Arlequin software. ViennaRNA v2.5.1 predicted the haplotype mRNA secondary structure. We evaluated the correlation between mRNA secondary structure changes and ventricular septal defects. Results The chi(2) results showed that the allele frequency of FLT4 rs383985 (P = 0.040) was different between the control group and the case group (P < 0.05). FLT4 rs3736061 (r(2) = 1), rs3736062 (r(2) = 0.84), rs3736063 (r(2) = 0.84) and FLT4 rs383985 were in high linkage disequilibrium (r(2) > 0.8). Among them, rs3736061 and rs3736062 SNPs in the FLT4 gene led to synonymous variations of amino acids, but predicting the secondary structure of mRNA might change the secondary structure of mRNA and reduce the free energy. Conclusions These findings suggest a possible molecular pathogenesis associated with isolated VSD, which warrants investigation in future studies.