Chronic mitral regurgitation (MR) is associated with adverse clinical outcomes, and the role of renin-angiotensin system inhibitors (RASI) in patients with MR remains uncertain. This study evaluated the association between RASI use patterns and 2-year all-cause mortality and disease progression in patients with primary MR (PMR) and secondary MR (SMR). This registry-based study included 3,297 patients with moderate-to-severe chronic MR from the China Valvular Heart Disease registry, including 955 with PMR and 2,342 with SMR. RASI use was assessed at baseline and during follow-up, and patients were categorized as always users, never users, or inconsistent users. The primary endpoint was 2-year all-cause mortality. The secondary endpoint was change in MR severity. Associations between RASI use and outcomes were assessed using multivariable Cox regression, propensity-score matching, and time-varying Cox analyses. Consistent RASI use was associated with lower 2-year all-cause mortality in both PMR and SMR. In multivariable Cox regression, never users had higher mortality risk than always users in both cohorts (PMR: HR 5.40, 95

Although oxidative stress (OS) links to the pathogenesis of coronary artery disease (CAD), its underlying genetic mechanisms remain unclear. Through summary data-based Mendelian randomization (SMR) and colocalization, this research seeks to assess the potential causal links between OS-related genes and CAD. Summary-level data on the methylation, expression, and protein abundance levels of OS-related genes were obtained from the corresponding quantitative trait loci (QTL) studies. We obtained genome-wide association study summary statistics for CAD from a previous study (discovery), the FinnGen and UK Biobank (replication). Two-sample MR analysis was conducted to verify the associations between key genes expressions and meta-analysis cohort of CAD risk. Mediation analysis was conducted to evaluate the mediating role of gene expression variation in the causal pathway linking methylation levels of key loci to the risk or progression of the disease. We identified 35 methylation loci, 7 genes, and 12 proteins in the discovery cohort. By integrating multiomic data, we identified SMARCA4, NAGLU, SREBF1, RPTOR, and HLA-B as potential causal targets associated with CAD. The two-sample MR analysis once again confirmed that the expressions of the SMARCA4, SREBF1, and HLA-B genes in the meta-analysis cohort showed a significant association with the risk of CAD, and this association was consistent with the direction of the SMR. Furthermore, both the expression and methylation of SMARCA4 were positively associated with CAD, and the direct and indirect effects of SMARCA4 methylation were confirmed. In summary, our results identified potential causal associations between SMARCA4, NAGLU, SREBF1, RPTOR, HLA-B, and CAD. The findings highlight the necessity for further exploration into the underlying etiology of CAD.

BACKGROUND:Transcatheter aortic valve replacement (TAVR) has transformed the treatment of severe aortic stenosis in patients at high or prohibitive surgical risk. Despite high procedural success, postoperative complications remain common and clinically consequential. Understanding how research on these complications has evolved is essential for guiding future investigations and improving outcomes. This study maps the global research landscape of TAVR-associated postoperative complications, with emphasis on thematic evolution, collaboration patterns, and emerging mechanistic and analytical approaches. METHODS:A bibliometric analysis of publications from 2006 to 2025 was conducted using the Web of Science Core Collection. Publication trends, contributing countries and institutions, authors, subject categories, and journals were analysed. CiteSpace and VOSviewer were used to visualise keyword co-occurrence, citation bursts, collaboration networks, and thematic clusters. RESULTS:A total of 3587 publications were identified, with rapid growth after 2014. The United States led in publication output and international collaboration, followed by Germany, Italy, and the United Kingdom. Research themes shifted from early feasibility studies towards complication-focused topics. High-frequency keywords included stroke, paravalvular leak, and bundle branch block, while recent attention has increasingly focused on frailty, sarcopenia, and multimorbidity. Biomechanical terms such as finite element and fluid-structure interaction reflected deeper mechanistic exploration. The literature spanned over 20 disciplines, indicating strong interdisciplinarity. CONCLUSIONS:The field has shifted from procedural feasibility to multidisciplinary, mechanism-oriented studies of complications affecting long-term outcomes, with frailty emerging as a key patient-centred determinant in older TAVR populations.

PURPOSE:Coronary artery disease (CAD) is a leading cause of cardiovascular morbidity and mortality worldwide. Recent studies suggest disruptions in circadian rhythms may contribute to CAD, but the underlying mechanisms remain unclear. This study employs summary-data-based Mendelian randomization to explore the roles of circadian rhythm genes in CAD and their clinical implications. METHODS:We retrieved circadian rhythm-related genes from the GeneCards database and utilized genome-wide association study summary data for CAD from the IEU database, further validated with FinnGen and UK Biobank datasets. We integrated expression quantitative trait loci (eQTL), methylation quantitative trait loci (mQTL), and protein abundance quantitative trait loci (pQTL) data to assess causal associations with CAD. Colocalization analysis confirmed that the signals originated from the same genetic variants. RESULTS:Our analyses identified 49 mQTLs, 11 eQTLs, and one pQTL causally associated with CAD. Integration of mQTL and eQTL data revealed 13 methylation sites and eight key genes, particularly RASD1 (OR = 0.777, 95% CI: 0.672-0.898) and SREBF1 (OR = 0.893, 95% CI: 0.844-0.946). The DNA methylation level at site cg20122488 was negatively correlated with RASD1 expression, while eQTL data for SREBF1 indicated a regulatory relationship with CAD risk. CONCLUSIONS:This study emphasizes the significant roles of circadian rhythm genes RASD1 and SREBF1 in CAD pathogenesis. Findings suggest therapeutic potential for these genes, warranting further research to validate their functions and inform preventive and treatment strategies. Key messages What is already known Coronary artery disease (CAD) is a leading global cause of cardiovascular mortality, with circadian rhythm disruptions increasingly implicated in its pathogenesis, though causal genetic mechanisms remain unclear. What this study adds This Mendelian randomization study identifies 13 methylation sites and eight key circadian-related genes (e.g. RASD1, SREBF1) with causal links to CAD, revealing specific epigenetic and transcriptional regulatory effects on disease risk. How this study might affect research, practice, or policy The findings highlight circadian rhythm genes as potential therapeutic targets, offering novel insights for CAD prevention strategies and guiding future research into circadian-based interventions.

BACKGROUND:Valvular heart disease (VHD) is a major cause of cardiovascular morbidity and mortality worldwide. The impact of environmental stress on the prognosis of patients with VHD is unknown. This study aims to explore the impact of ambient air pollution exposure on the clinical outcomes of patients with VHD. METHODS:Data were derived from the China-VHD registry, a national multicentre prospective cohort study. Monthly ambient particulate matter with a diameter <2.5 μm (PM2.5) exposure was derived from the ChinaHighAirPollutants (CHAP) dataset at 1×1 km resolution. Using residential address, clinical data from patients diagnosed with VHD between April and June 2018 were linked to ambient PM2.5 exposure concentrations. Patients were followed up until they lost or experienced the primary outcome (defined as all-cause mortality or heart failure hospitalisation) for 2 years. Time-varying Cox proportional hazards regression models were applied to evaluate the association between monthly ambient PM2.5 exposure and outcomes. RESULTS:A total of 12 258 VHD patients were included. Mean age at enrolment was 61.2±13.7 years, and 54.7% were male. Mean baseline ambient PM2.5 exposure was 43.50±12.25 µg/m3. After 2 years of follow-up, 1577 patients (12.9%) experienced the primary outcome. The estimated HR for all-cause mortality or heart failure hospitalisation was 1.24 (95% CI 1.07 to 1.43) for individuals in the highest tertile of monthly ambient PM2.5 exposure compared with those in the lowest tertile. Each IQR (21.80 µg/m³) increase in monthly ambient PM2.5 exposure was associated with a 1.11-fold higher risk of the primary outcome (95% CI 1.04 to 1.18). This association was consistent across subgroups. CONCLUSIONS:Exposure to air pollution was associated with adverse outcomes in patients with VHD. These findings highlight the potential role of a key environmental factor in the progression and prognosis of VHD. TRIAL REGISTRATION NUMBER:NCT03484806.

BACKGROUND:Long-term mortality remains unsatisfactorily high after transcatheter aortic valve replacement (TAVR). Conventional risk models are limited in capturing subclinical electrophysiological alterations associated with poor prognosis, which can be identified on routine preoperative electrocardiograms. OBJECTIVES:The authors aim to develop and validate an artificial intelligence-enhanced electrocardiogram (AI-ECG) model for predicting long-term mortality in post-TAVR patients. METHODS:A total of 711 patients with severe aortic stenosis undergoing TAVR were enrolled from 2 centers. Patients from one center were divided into training and internal validation sets (7:3), and participants from another center served as the external validation cohort. Preoperative electrocardiogram images were analyzed using a Residual Network-18 model to generate mortality risk stratification. The primary endpoint was 3-year all-cause death. RESULTS:The AI-ECG model demonstrated comparable discrimination between the internal and external patient cohorts, with areas under the receiver operating characteristics curve of 0.767 (95% CI: 0.657-0.877) vs 0.712 (95% CI: 0.627-0.795) (P for DeLong test = 0.428). High-risk patients (15.5% [39 of 251]) exhibited a 61.5% (24 of 39, 95% CI: 42.8%-74.1%) 3-year mortality rate vs 16.5% (35 of 212, 95% CI: 11.4%-21.4%) in low-risk patients (84.5% [212 of 251]) (log-rank P < 0.001). Adjusted for comorbidities, high-risk classification independently predicted mortality (adjusted HR: 3.49; 95% CI: 1.96-6.22). Subgroup analysis did not reveal significant interaction effects of the AI-ECG model across different patient populations. Decision curve analysis confirmed clinical net benefit across threshold probabilities (0.05-0.60). CONCLUSIONS:The AI-ECG model provides noninvasive and accurate long-term risk stratification for TAVR patients, with promising clinical application value for individualized follow-up management.

BACKGROUND:Lipoprotein(a) (Lp[a]) has been identified as a significant risk factor for aortic stenosis (AS). However, its impact on outcomes post-transcatheter aortic valve replacement (TAVR) remains unknown. OBJECTIVE:To investigate the association between Lp(a) levels and long-term outcomes as well as its impact on the bioprosthetic valve degeneration in patients post-TAVR. METHODS:Patients with severe AS who underwent TAVR were consecutively recruited. Lp(a) was measured before TAVR procedure. The subjects were divided according to levels of Lp(a). The outcomes were all-cause mortality and possible structural valve degeneration (SVD) measured by Doppler echocardiography. Cox regression models and competing risk models were used to explore the association between Lp(a) levels and outcomes. RESULTS:Of the 601 included patients (mean age: 75.5 ± 7.2, male: 58.7%), 137 patients (22.7%) experienced mortality after a median follow-up of 3.9 years. After multivariable adjustment, elevated Lp(a) (defined as ≥30 mg/dL) was identified as an independent predictor of all-cause mortality (hazard ratio [HR]: 1.81, 95% CI: 1.27-2.57, P = .001) and cardiovascular mortality (HR: 2.02, 95% CI: 1.12-3.66, P = .020). Elevated Lp(a) was also associated with increased risk of possible SVD (subdistribution HR: 3.40, 95% CI: 1.32-8.79, P = .012). Using a threshold value of 50 mg/dL for elevated Lp(a) still supported the main findings. CONCLUSION:Elevated baseline Lp(a) levels are associated with poor clinical outcomes and possible SVD in patients with severe AS undergoing TAVR. Further research is warranted to confirm these findings.

Background The optimal timing of transcatheter aortic valve replacement (TAVR) for asymptomatic or minimally symptomatic patients with severe aortic stenosis (AS) remains controversial. Microvascular dysfunction and increased microcirculatory resistance have been linked to adverse outcomes in AS, suggesting that resting angiographic microvascular resistance (AMRr) may aid in identifying higher-risk patients. Method We conducted a retrospective study of 180 severe AS patients who underwent TAVR at Fuwai Hospital between 2012 and 2021. Patients were grouped based on an AMRr cutoff value of 490, identified through receiver operating characteristic (ROC) analysis. The primary endpoint was the incidence of major adverse cardiovascular events (MACE), including all-cause mortality, heart failure, and myocardial infarction. Kaplan-Meier and Cox regression analyses were used to compare outcomes between groups. Results A total of 180 asymptomatic or minimally symptomatic AS patients undergoing TAVR were enrolled. After a 40-month follow-up, the AMRr >490 group had a higher MACE risk, mainly driven by readmission for heart failure. Additionally, continuous analysis indicated that every 100-unit increase in AMRr was associated with an 18 %, 17 %, and 1.58-fold increased risk of MACE, all-cause mortality, and NOAF, respectively. Moreover, the addition of AMRr to a clinical model significantly improved the prediction of MACE (AUC 0.678 vs. 0.582, p = 0.023). Conclusion Asymptomatic or minimally symptomatic AS patients with AMRr >490 had a significantly higher incidence of MACE and heart failure rehospitalization than those with AMRr ≤490 after TAVR. The inclusion of AMRr in a predictive model improved the accuracy for long-term MACE, demonstrating an incremental prognostic value.

Background::Valvular heart disease (VHD) has become increasingly common with the aging in China. This study aimed to evaluate regional differences in the clinical features, management strategies, and outcomes of patients with VHD across different regions in China.Methods::Data were collected from the China-VHD Study. From April 2018 to June 2018, 12,347 patients who presented with moderate or severe native VHD with a median of 2 years of follow-up from 46 centers at certified tertiary hospitals across 31 provinces, autonomous regions, and municipalities in Chinese mainland were included in this study. According to the locations of the research centers, patients were divided into five regional groups: eastern, southern, western, northern, and central China. The clinical features of VHD patients were compared among the five geographical regions. The primary outcome was all-cause mortality or rehospitalization for heart failure. Kaplan–Meier survival analysis was used to compare the cumulative incidence rate.Results::Among the enrolled patients (mean age, 61.96 years; 6877 [55.70%] male), multiple VHD was the most frequent type (4042, 32.74%), which was mainly found in eastern China, followed by isolated mitral regurgitation (3044, 24.65%), which was mainly found in northern China. The etiology of VHD varied significantly across different regions of China. The overall rate of valve interventions was 32.67% (4008/12,268), with the highest rate in southern China at 48.46% (205/423). In terms of procedure, the proportion of transcatheter valve intervention was relatively low compared to that of surgical treatment. Patients with VHD in western China had the highest incidence of all-cause mortality or rehospitalization for heart failure. Valve intervention significantly improved the outcome of patients with VHD in all five regions (all P <0.05). Conclusions::This study revealed that patients with VHD in China are characterized by significant geographic disparities in clinical features, treatment, and clinical outcomes. Targeted efforts are needed to improve the management and prognosis of patients with VHD in China according to differences in geographical characteristics.Registration::ClinicalTrials.gov, NCT03484806.

Background Stress hyperglycemia ratio (SHR) has recently been recognized as a novel biomarker that accurately reflects acute hyperglycemia status and is associated with poor prognosis of heart failure. We evaluated the relationship between SHR and clinical outcomes in patients with severe aortic stenosis receiving transcatheter aortic valve replacement (TAVR). Methods There were 582 patients with severe native aortic stenosis who underwent TAVR consecutively enrolled in the study. The formula used to determine SHR was as follows: admission blood glucose (mmol/L)/(1.59×HbA 1c [%]–2.59). The primary endpoint was defined as all-cause mortality, while secondary endpoints included a composite of cardiovascular mortality or readmission for heart failure, and major adverse cardiovascular events (MACE) including cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. Multivariable Cox regression and restricted cubic spline analysis were employed to assess the relationship between SHR and endpoints, with hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a median follow-up of 3.9 years, a total of 130 cases (22.3%) of all-cause mortality were recorded. Results from the restricted cubic spline analysis indicated a linear association between SHR and all endpoints (p for non-linearity > 0.05), even after adjustment for other confounding factors. Per 0.1 unit increase in SHR was associated with a 12% (adjusted HR: 1.12, 95% CI: 1.04–1.21) higher incidence of the primary endpoint, a 12% (adjusted HR: 1.12, 95% CI: 1.02–1.22) higher incidence of cardiovascular mortality or readmission for heart failure, and a 12% (adjusted HR: 1.12, 95% CI: 1.01–1.23) higher incidence of MACE. Subgroup analysis revealed that SHR had a significant interaction with diabetes mellitus with regard to the risk of all-cause mortality (p for interaction: 0.042). Kaplan-Meier survival analysis showed that there were significant differences in the incidence of all endpoints between the two groups with 0.944 as the optimal binary cutoff point of SHR (all log-rank test: p < 0.05). Conclusions Our study indicates linear relationships of SHR with the risk of all-cause mortality, cardiovascular mortality or readmission for heart failure, and MACE in patients with severe aortic stenosis receiving TAVR after a median follow-up of 3.9 years. Patients with an SHR exceeding 0.944 had a poorer prognosis compared to those with lower SHR values.

BACKGROUND:We aim to compare the short and long-term outcomes for aortic stenosis (AS) patients undergone TAVR with and without ascending aorta dilation (AAD). METHODS:Consecutive patients diagnosed with native severe AS who underwent TAVR from September 2012 to September 2021 were enrolled. They were stratified into the moderate/severe dilation group (greatest ascending aorta width ≥ 45 mm) and the non/mild dilation group. Survival outcomes were illustrated using Kaplan-Meier curves and evaluated with the log-rank test. Data from patients with CT follow-up of >6 months was used to investigate the progression rate of AAD. RESULTS:The study cohort comprised 556 patients, with a mean age of 75.5 ± 7.3 years. Among them, 107 patients (19.2%) had a moderate/severe AAD (≥45 mm), with an average diameter of 48.6 mm (±2.8). During hospitalization, both groups witnessed two cases of ascending aortic dissection (1.9% vs 0.4%, P = 0.380). The median follow-up duration was 3.9 years (95% CI: 3.8-4.0 years). No deaths were caused by aortic events and no patients experienced a new aortic dissection. The AAD cohort's 4-year all-cause and cardiovascular mortality rates were not significantly different to the non/mild dilation group's (log-rank test, P = 0.109 and P = 0.698, respectively). Follow-up CT data revealed that the rate of aortic dilation progression in the moderate/severe dilation group was not significantly different from that in the non/mild group (0.0 mm/year, 25-75%th: -0.3-0.2 vs 0.1 mm/year, 25-75%th: -0.3-0.4, P = 0.122). CONCLUSION:This study found no significant difference regarding short-term and long-term outcomes in AS patients with/without moderate/severe AAD undergoing TAVR.