China has prioritized the prevention of cardiovascular disease. Over the past decade, significant investments have been made in public health services, along with the implementation of various health promotion policy agendas. As a result, environmental cardiovascular hazards have been substantially reduced, and care coverage within the primary health care system has improved. Nevertheless, adherence to various healthy lifestyles within the population has exhibited different secular trends, meanwhile the underutilization of secondary prevention medications among vulnerable populations is concerning. The Healthy China Initiative 2030 outlines a roadmap to prevent, pre-empt, and mitigate cardiovascular disease. China, along with other developing countries facing similar challenges, should consider fostering supportive social environments for healthy behaviors, targeting vulnerable groups for lifestyle adherence and access to care, expanding the scope of services provided by primary care providers, leveraging new technologies to develop scalable tools, and integrating surveillance systems for health promotion and care.

BACKGROUND:Heart failure is associated with renal function decline and increased morbidity and death. We evaluated the association of systolic blood pressure control over time, measured by time in target range (TTR), with renal function decline and death in patients with heart failure. METHODS:We analyzed a multicenter prospective cohort of patients hospitalized for heart failure across 52 hospitals in China between 2016 and 2018. Systolic blood pressure was measured at 1, 6, and 12 months after discharge. The 12-month systolic blood pressure TTR was calculated by linear interpolation for a target range of 110 to 130 mm Hg. Outcomes were 1-year renal function decline (≥20% reduction in estimated glomerular filtration rate from 1 to 12 months plus estimated glomerular filtration rate <60 mL/min per 1.73 m2 at 12 months) and 5-year all-cause death. RESULTS:The analysis included 1529 patients for renal function decline and 2195 patients for death. Median follow-up was 1.0 and 4.2 years, respectively. Renal function decline and death decreased significantly from the lowest to highest TTR tertile (Ptrend<0.001 and 0.009, respectively), supported by restricted cubic spline analyses. After multivariable adjustment, each 1-SD increase in TTR (35%-36%) was associated with lower risks of renal function decline (odds ratio, 0.74 [95% CI, 0.60-0.93]; P=0.008) and all-cause death (hazard ratio, 0.90 [95% CI, 0.83-0.98]; P=0.01). Results were consistent across subgroups, using 6-month TTR, and for cardiovascular death. CONCLUSIONS:Better long-term systolic blood pressure control, assessed by TTR, was independently associated with lower risks of renal function decline and long-term death in patients with heart failure. REGISTRATION INFORMATION:clinicaltrials.gov Identifier: NCT02878811.

Accurate quantification of aortic valve calcification (AVC) on contrast-enhanced computed tomography angiography (CTA) is pivotal for planning surgical and transcatheter aortic valve replacement. The optimal Hounsfield unit (HU) threshold for calcification detection on contrast-enhanced images remains unresolved, and every prior validation study has relied on non-contrast Agatston scoring—itself an imaging estimate—as the reference standard. This study validated two widely used fixed HU thresholds (450 HU and 850 HU) and a self-configuring nnU-Net deep learning model against ex vivo gravimetric calcium weight as an absolute physical ground truth. Four hundred patients were included in a retrospective cohort study with a pre-specified temporal validation split: 300 with CT-confirmed AVC and 100 with normal aortic valves. Fifty chronologically later AVC patients who underwent elective open surgical aortic valve replacement (SAVR) within seven days of clinically indicated pre-operative contrast-enhanced CTA formed the locked surgical validation cohort; their excised native leaflets underwent standardised high-temperature ashing (550 °C, 12 h) and analytical weighing (precision 0.1 mg) to obtain gravimetric calcium mass. The remaining 350 cases served exclusively for nnU-Net development (280 training / 70 internal validation). CT-derived calcium mass-equivalent estimates were quantified on the validation cohort and compared with gravimetric weight using Pearson and Spearman correlation and Bland-Altman analysis. The nnU-Net achieved the strongest observed correlation with gravimetric weight (Pearson r = 0.967; bias + 6.2 mg; RMSE 13.7 mg), significantly outperforming the 450 HU threshold for correlation (r = 0.864; bias + 36.2 mg; RMSE 42.1 mg; Steiger p < 0.001) and showing a non-significant trend toward stronger correlation than 850 HU (r = 0.929; bias + 17.5 mg; RMSE 23.9 mg; Steiger p = 0.085). Compared with 850 HU, nnU-Net provided lower bias and RMSE, although the difference in Pearson r did not reach statistical significance. The 450 HU method exhibited significant proportional bias (p = 0.024), whereas neither 850 HU nor nnU-Net did. The nnU-Net achieved a mean Dice coefficient of 0.873 and intersection-over-union of 0.812. Against physically weighed calcium, nnU-Net deep learning segmentation provided the most favourable overall performance profile on contrast-enhanced CTA, with the lowest bias and RMSE and the strongest observed correlation. The improvement in Pearson correlation over 850 HU represented a non-significant trend, whereas the error and agreement metrics favoured nnU-Net. Among fixed thresholds, 850 HU substantially outperformed 450 HU, offering direct physical-rather than surrogate imaging-evidence to support 850 HU as the preferred fixed threshold in standard contrast-enhanced protocols.

BACKGROUND:Inadequate blood pressure (BP) control remains a major public health challenge worldwide. Rigorous evidence is lacking on how to implement targeting systolic BP (SBP) <120 mm Hg in real-world settings. OBJECTIVES:We aimed to examine the implementation and effect heterogeneity of targeting SBP <120 mm Hg in diverse hypertensive patients with high cardiovascular risk, particularly those with longstanding uncontrolled BP. METHODS:Using data from the ESPRIT (Effects of intensive Systolic blood Pressure lowering treatment in reducing RIsk of vascular evenTs) trial, we analyzed achieved average BP level, time to intensive control, medication use, clinic visit frequency, major vascular events, all-cause death, and safety outcomes among all participants and across subgroups. RESULTS:We included 11,255 participants (mean age: 64.6 ± 7.1 years; 41.3% women). The achieved median SBP of the intensive arm was 117 mm Hg (IQR: 113-123 mm Hg) in all participants, with 62.5% of participants in the intensive arm achieving intensive BP control. Older participants, male and those with a higher baseline SBP, longer hypertension duration, history of stroke and diabetes, and used more antihypertensive medications at baseline were less likely to achieve sustained intensive control. The median time to intensive control was 62 days (IQR: 33-96 days), and higher baseline SBP levels, obesity, or diabetes were associated with a longer time to reach intensive control. At the 1-year visit, the medication equivalent was 3.3 in the intensive arm and 2.0 in the standard arm. Male, obese, diabetic patients and those with hypertension duration ≥10 years or baseline SBP ≥140 mm Hg required more medications. Clinic visit frequency in the first year was 6.9 and 5.4 for intensive and standard arms, respectively, and visits decreased during the following years. There was no significant interaction between treatment effects and subgroups of hypertension duration and baseline SBP combination (all P for interaction > 0.05), except for myocardial infarction (P for interaction = 0.019). CONCLUSIONS:For the diverse hypertensive patients with high cardiovascular risk, including those with longstanding uncontrolled BP, sustaining SBP <120 mm Hg is achievable with modest additional medical resources. Applying ESPRIT evidence could improve BP control and reduce cardiovascular burden globally. (Effects of Intensive Systolic Blood Pressure Lowering Treatment in Reducing RIsk of Vascular events Study [ESPRIT]; NCT04030234).

Importance Clinical decision support systems (CDSSs) are increasingly used to improve guideline-based hypertension care; however, their association with antihypertensive treatment intensification and blood pressure (BP) control in primary care practices remains unclear. Objectives To evaluate whether CDSS implementation was associated with improvement in antihypertensive treatment intensification and BP control in primary care practices and to examine the association between treatment intensification and BP change. Design, Setting, and Participants This post hoc secondary analysis used the data from a pragmatic cluster randomized clinical trial conducted from August 1, 2019, to July 31, 2022, in urban primary care practices in China among 4612 adult patients with hypertension and uncontrolled BP at baseline. Data analysis was conducted from August 1, 2024, to September 1, 2025. Interventions Practices randomized to the intervention group used a real-time, guideline-based CDSS for guiding antihypertensive treatment, while control practices delivered usual care. Main Outcomes and Measures Treatment intensification rate, defined as the percentage of clinic visits with uncontrolled BP during which there was an increase in the class or dose of antihypertensive medication. Among patients with uncontrolled BP at baseline, treatment intensification was assessed at visits with uncontrolled BP, and BP control was evaluated at the last follow-up visit. Treatment intensity was summarized using a treatment intensification score reflecting the frequency of medication intensification relative to guideline expectations. Results Among 4612 patients with uncontrolled BP at baseline (median age, 63 years [IQR, 52-74 years]; 2648 men [57.4%]; 2134 [46.3%] in CDSS group and 2478 [53.7%] in control group) from 93 practices, treatment intensification rates were higher in the CDSS group than in the usual care group (47.3% [95% CI, 40.1%-54.6%] vs 11.6% [95% CI, 8.9%-14.9%]; adjusted odds ratio [OR], 6.87 [95% CI, 4.90-9.64]; P < .001). The median treatment intensification score was higher in the CDSS group than in the usual care group (–0.25 [IQR, –0.50 to 0] vs –0.50 [IQR, –0.75 to –0.30]; mean difference, 0.22 [95% CI, 0.17-0.28]). Each 0.22-point increase in the treatment intensification score was associated with a mean systolic BP change of −3.8 mm Hg (95% CI, −4.1 to −3.5 mm Hg). BP control rates were similar between groups. Conclusions and Relevance In this post hoc analysis of a cluster randomized clinical trial, CDSS implementation was associated with increased treatment intensification but was not associated with improvements in overall BP control. These findings suggest that stronger implementation strategies may be needed to translate treatment intensification into improved BP outcomes. Trial Registration ClinicalTrials.gov Identifier: NCT03636334

BACKGROUND:The impact of intensive blood pressure (BP) control on cognitive function in East Asian populations remains uncertain. We aimed to assess the effect of a lower systolic BP target on global cognitive function in Chinese hypertensive adults. METHODS:This secondary analysis of a randomized trial involved hypertensive patients with high cardiovascular risk across 116 sites in China. Participants were assigned to receive intensive treatment (systolic BP target <120 mm Hg) or standard treatment (systolic BP target <140 mm Hg) for a median of 3.4 years. Cognitive function was assessed via MMSE (Mini-Mental State Examination) at baseline and the end of the study. Prespecified outcomes were a change in MMSE score and investigator-reported probable dementia. RESULTS:Among 11 255 randomized participants, all completed cognitive assessment at baseline and 10 440 (92.8%) at the end of the study. The mean change in MMSE score was not significantly different between arms (difference, 0.05 [95% CI, -0.07 to 0.17]), with a mean change of -0.54 (95% CI, -0.63 to -0.46) in the intensive arm and -0.60 (95% CI, -0.68 to -0.51) in the standard arm. Results were robust across sensitivity analyses and consistent across most subgroups. Exceptions included subgroups of coronary heart disease or antiplatelet treatment. The incidence of probable dementia was too low for meaningful interpretation. CONCLUSIONS:Intensive systolic BP lowering to a target of <120 mm Hg for 3 years did not adversely affect global cognitive function in Chinese hypertensive adults, irrespective of age, sex, BP level, and comorbidities, affirming the cognitive safety of this treatment strategy. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04030234.

Background: Degenerative mitral regurgitation (DMR) is a cardiovascular condition marked by progressive degeneration of the mitral valve, leading to complications such as heart failure and atrial fibrillation. Despite advancements, research trends and knowledge gaps remain inadequately addressed. Therefore, this study aimed to perform a comprehensive bibliometric analysis of DMR-related research to identify publication trends, influential contributors, and emerging research themes. Methods: A bibliometric analysis was conducted on articles related to DMR published from 2004 to 2024, retrieved from the Web of Science Core Collection (WoSCC) database. Data were analyzed using Microsoft Excel, R-bibliometrix, VOSviewer, and CiteSpace to evaluate publication trends, international collaborations, key contributors, and emerging research themes. Results: A total of 2,349 publications were identified, with an annual growth rate of 4.07%, involving 12,474 contributors from 79 countries. The USA led with 726 publications and 37,386 citations. Leading institutions included Mayo Clinic and Harvard University. The top journals were the Journal of the American College of Cardiology, Circulation, and The Journal of Thoracic and Cardiovascular Surgery. The most influential author was Enriquez-Sarano Maurice, followed by Delling Francesca N. and Pepi Mauro. Keyword analysis identified central themes such as "regurgitation", "surgery", and "echocardiography", with emerging topics like "mitral valve repair" and "transcatheter interventions". Conclusions: This bibliometric analysis highlights significant advancements in DMR research, particularly in surgical techniques and imaging modalities, and provides a foundation for future studies aimed at improving patient outcomes.

Background For patients with pure aortic regurgitation (AR) with low left ventricular ejection fraction (LVEF), the net clinical benefit of current treatment options remains uncertain. Our goal was to evaluate the clinical outcomes of TAVR in such patients and the periprocedural clinical value of extracorporeal membrane oxygenation (ECMO). Methods In this multicenter study, patients who underwent TAVR between June 2017 and May 2021 were enrolled. Patients were divided into three groups based on LVEF and whether they received preventive ECMO. The primary endpoint was 2-year all-cause mortality. Results A total of 751 patients were included, including 51 patients (6.8%) in the ECMO + LVEF < 35% group, 38 patients (5.1%) in the non-ECMO + LVEF < 35% group, and 662 patients (88.1%) in the non-ECMO + LVEF > 35% group. The three groups with LVEF were 26.0 (24.0–32.0)%, 33.0 (30.0–34.0)%, and 52.0 (48.0–57.0)%. The primary endpoint of patients with LVEF < 35% was similar to that of patients with LVEF > 35% (Hazard ratio: 1.18; 95% CI: 0.69–2.03, P = 0.547). The 2-year LVEF of patients with LVEF < 35% was significantly increased. Notably, the ECMO + LVEF < 35% group had a lower incidence of the primary endpoint than the non-ECMO + LVEF < 35% group (hazard ratio: 0.47; 95% confidence interval: 0.17–0.82, P = 0.042). Conclusions The 2-year clinical outcomes among the three groups were similar, and LVEF was significantly improved. Timely implantation of ECMO had potential clinical value for these patients.

OBJECTIVES:We evaluated the safety and efficacy of transcatheter aortic valve replacement (TAVR) up to 1-year follow-up for patients with severe pure aortic valve regurgitation (AR) or mixed severe aortic valve regurgitation and aortic valve stenosis (AR+AS) using a novel self-expandable bioprosthesis. METHODS:From 2021 to 2022, transapical TAVR using Ken-Valve (Jenscare Biotechnology Ltd, Ningbo, China) was performed in 142 symptomatic patients (mean age 70.3 ± 5.5 years) with pure AR (n = 109) or AR+AS (n = 33) across 15 hospitals in China. All patients were considered high-risk or inoperable after heart team evaluation, with a mean Society of Thoracic Surgeons score of 5.9 ± 3.0%, and 99.3% in NYHA class III/IV. Procedural characteristics, echocardiography data, and clinical outcomes up to 1-year were analysed. RESULTS:Technical success was achieved in 97.2% of cases. Two (1.4%) patients were converted to open surgery due to unsuitable anatomy or valve migration during the procedure. New permanent pacemakers were implanted in 20 (14.1%) patients. Three (2.1%) patients had stroke, and 3 (2.1%) patients had major bleeding. Thirty-day mortality was 2.1%, and all-cause mortality at 1-year was 5.6% (8/142). Mean aortic valve gradient and effective orifice area (EOA) at 1-year postoperatively were 9.4 ± 5.4 mmHg and 1.9 ± 0.6 cm2, respectively. Significant improvement in clinical symptoms, positive left ventricular remodelling, and quality of life were observed up to 1-year. There was no significant difference in mortality, complications, and haemodynamic performance between patients with pure AR and AR+AS at 1-year. CONCLUSIONS:TAVR using the Ken-Valve was safe and effective in patients with pure AR or mixed AR+AS in mid-term. CLINICAL REGISTRATION NUMBER:NCT03788590.

Transcatheter aortic valve replacement (TAVR) induces anatomical changes in the aortic root; however, the hemodynamic relevance of post-procedural geometric remodeling remains incompletely understood. We retrospectively analyzed 117 patients with severe aortic stenosis who underwent transapical TAVR using the self-expanding Xcor system (Saint Medical Technology, Nanjing, China) and had paired pre-procedural and 1-year post-procedural computed tomography angiography (CTA). Changes in aortic root dimensions and annulus angle were quantified. Hemodynamic outcomes were assessed by 1-year echocardiography. A composite adverse hemodynamic outcome was defined as mean pressure gradient ≥ 20 mmHg or Doppler velocity index < 0.35. At 1 year, TAVR resulted in statistically significant but modest expansion of the sinus of Valsalva (+ 2.6 mm, + 6.8

Importance:Berberine is a potential therapy for metabolic disorders, yet its effects on visceral adipose tissue (VAT) and liver fat remain uncertain. Objectives:To evaluate the efficacy and safety of berberine in reducing VAT area and liver fat content in diabetes-free individuals with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Design, Setting, and Participants:In this multicenter, double-blind randomized clinical trial, diabetes-free individuals with obesity and MASLD were enrolled at 11 hospitals in China between July 6 and December 29, 2023, with a follow-up duration of 6 months. Interventions:Participants were randomly assigned to receive either oral berberine, 1 g/d, or a matching placebo. Main Outcomes and Measures:The primary outcomes were relative percentage change in VAT area and absolute change in liver fat content assessed by computed tomography. Other outcomes included changes in parameters of glucose, lipids, and inflammation. Analyses were conducted according to the intention-to-treat principle. Results:Among 337 randomized participants (mean [SD] age, 41.8 [10.6] years; 221 [65.6%] male), 169 received berberine and 168 placebo. The mean (SD) medication adherence rates were 90.3% (14.7%) for berberine and 90.7% (17.4%) for placebo. No significant differences were observed between study arms for VAT area (1.4% [97.5% CI, -2.4% to 5.2%]) or liver fat content (0.9% [97.5% CI, -0.4% to 2.1%). Berberine was associated with larger reductions in low-density lipoprotein cholesterol (-7.72 [95% CI, -13.13 to -1.93] mg/dL), apolipoprotein B (-3.42 [95% CI, -6.33 to -0.51] mg/dL) and high-sensitivity C-reactive protein (hs-CRP) (-0.072 [95% CI, -0.140 to -0.004] mg/dL) vs placebo, but not other secondary outcomes. The incidence of adverse events was similar between study arms. Post hoc analyses suggested consistent patterns of larger reductions in low-density lipoprotein cholesterol, apolipoprotein B, and hs-CRP levels in participants with higher baseline hs-CRP levels. Conclusions and Relevance:In this randomized clinical trial of diabetes-free individuals with obesity and MASLD, a 6-month berberine treatment at a daily dose of 1 g had an excellent safety profile but did not reduce VAT area or liver fat content. Trial Registration:ClinicalTrials.gov Identifier: NCT05647915.

Introduction and objectivesLeft ventricular reverse remodeling (LVRR) after transcatheter aortic valve replacement (TAVR) is associated with outcomes, but the relevance of aortic-root geometry remains uncertain. We examined whether the annular eccentricity index (EI) and sinus of Valsalva height on computed tomography angiography (CTA) were associated with 1-year LVRR.MethodsThis retrospective secondary analysis included 115 patients with severe aortic stenosis from an 11-center cohort who underwent successful TAVR and survived to undergo evaluable preprocedural CTA and 1-year echocardiography. EI was calculated as the difference between maximum and minimum annular diameters divided by the maximum diameter. Sinus height was the mean perpendicular distance from the annular plane to the sinus tip across the three sinuses. LVRR was defined as an increase in left ventricular ejection fraction of at least 5 percentage points or a decrease in indexed left ventricular end-diastolic volume of at least 15%. A fixed multivariable logistic model adjusted for baseline ventricular function and clinical covariates; Firth bias-reduced logistic regression was used for primary inference because the smaller outcome group contained 37 patients, with conventional maximum-likelihood estimation as a sensitivity analysis.ResultsLVRR occurred in 78 patients (67.8%). In the primary Firth analysis, each 1-standard deviation (SD) decrease in EI was associated with higher odds of LVRR (adjusted odds ratio, 2.40; 95% confidence interval, 1.52–3.92; P < 0.001), as was each 1-SD increase in sinus height (adjusted odds ratio, 1.84; 95% confidence interval, 1.23–2.74; P = 0.003). Conventional maximum-likelihood estimates were directionally consistent. Model performance was lower after bootstrap optimism correction (area under the curve, 0.77 vs. 0.81 apparent).ConclusionsAmong patients who survived to undergo evaluable 1-year echocardiography, a lower EI and greater sinus height were associated with LVRR after TAVR. These hypothesis-generating associations require external validation before clinical application.

Importance:Clinical decision support systems (CDSSs) are increasingly used to improve guideline-based hypertension care; however, their association with antihypertensive treatment intensification and blood pressure (BP) control in primary care practices remains unclear. Objectives:To evaluate whether CDSS implementation was associated with improvement in antihypertensive treatment intensification and BP control in primary care practices and to examine the association between treatment intensification and BP change. Design, Setting, and Participants:This post hoc secondary analysis used the data from a pragmatic cluster randomized clinical trial conducted from August 1, 2019, to July 31, 2022, in urban primary care practices in China among 4612 adult patients with hypertension and uncontrolled BP at baseline. Data analysis was conducted from August 1, 2024, to September 1, 2025. Interventions:Practices randomized to the intervention group used a real-time, guideline-based CDSS for guiding antihypertensive treatment, while control practices delivered usual care. Main Outcomes and Measures:Treatment intensification rate, defined as the percentage of clinic visits with uncontrolled BP during which there was an increase in the class or dose of antihypertensive medication. Among patients with uncontrolled BP at baseline, treatment intensification was assessed at visits with uncontrolled BP, and BP control was evaluated at the last follow-up visit. Treatment intensity was summarized using a treatment intensification score reflecting the frequency of medication intensification relative to guideline expectations. Results:Among 4612 patients with uncontrolled BP at baseline (median age, 63 years [IQR, 52-74 years]; 2648 men [57.4%]; 2134 [46.3%] in CDSS group and 2478 [53.7%] in control group) from 93 practices, treatment intensification rates were higher in the CDSS group than in the usual care group (47.3% [95% CI, 40.1%-54.6%] vs 11.6% [95% CI, 8.9%-14.9%]; adjusted odds ratio [OR], 6.87 [95% CI, 4.90-9.64]; P < .001). The median treatment intensification score was higher in the CDSS group than in the usual care group (-0.25 [IQR, -0.50 to 0] vs -0.50 [IQR, -0.75 to -0.30]; mean difference, 0.22 [95% CI, 0.17-0.28]). Each 0.22-point increase in the treatment intensification score was associated with a mean systolic BP change of -3.8 mm Hg (95% CI, -4.1 to -3.5 mm Hg). BP control rates were similar between groups. Conclusions and Relevance:In this post hoc analysis of a cluster randomized clinical trial, CDSS implementation was associated with increased treatment intensification but was not associated with improvements in overall BP control. These findings suggest that stronger implementation strategies may be needed to translate treatment intensification into improved BP outcomes. Trial Registration:ClinicalTrials.gov Identifier: NCT03636334.

We sought to investigate whether remnant cholesterol (RC) modified the effect of intensive blood pressure (BP) lowering treatment. This study was a post hoc analysis of ESPRIT. In this trial, hypertensive patients with high cardiovascular risk were randomly assigned to intensive (systolic BP < 120 mmHg) or standard (systolic BP < 140 mmHg) treatment. Cox regression analysis was used to examine heterogeneity of treatment effect on the primary composite outcome (myocardial infarction, heart failure, stroke, coronary or non-coronary revascularization, or death from cardiovascular causes), individual components, and death from any cause in participants grouped by RC tertiles or the cut-off value (0.8 mmol/L). A total of 11,221 participants with complete data of baseline RC were included for analysis (females 41.3%, mean age 64.6 years). During a median follow-up of 3.3 years, 1163 primary outcomes occurred, and hazard ratios (HR) for the primary outcome were 0.98 (95% CI 0.80-1.20), 0.90 (95% CI 0.74-1.11), and 0.77 (95% CI 0.64-0.94) in the lowest, middle, and highest RC tertiles, respectively (P for interaction: 0.11). Additionally, intensive treatment only reduced the risk of myocardial infarction in the highest RC tertile (HR 0.56, 95% CI 0.36-0.89, P for interaction: 0.01). When grouping by RC level of 0.8 mmol/L, significant interactions were also noted for the primary outcome, myocardial infarction, death from cardiovascular causes, and death from any cause (all P for interaction <0.05). These results showed that effects of intensive treatment were shown to be modified by baseline RC level, and further research is needed to confirm our findings.

BACKGROUND:Mitochondrial dysfunction is implicated in mitral valve diseases (MVD), but specific genetically predicted genes and molecular mechanisms remain undefined. OBJECTIVE:We aimed to identify mitochondria-related genes driving rheumatic (RMVD) and non-rheumatic (NRMVD) MVD subtypes. METHODS:We performed a multi-omics Mendelian randomization (SMR) study integrating GWAS summary statistics for RMVD and NRMVD with blood DNA methylation (mQTL), gene expression (eQTL), and plasma protein (pQTL) data. Findings were evaluated using cardiac tissue transcriptomics (GTEx), explored in FinnGen, and further assessed by GEO tissue expression and protein-protein interaction (PPI) network analysis. RESULTS:Multi-omics and tissue-specific analyses consistently identified PCCB as a primary candidate risk gene for MVD, demonstrating risk-increasing effects across both blood and cardiac tissues. Independent GEO validation corroborated PCCB upregulation across diseased mitral valve and atrial myocardial tissues. Alongside PCCB, QRSL1 also exhibited consistent risk associations across blood and heart tissues. Exploratory FinnGen validation suggested nominal associations for PCCB and TRMU, though limited by phenotypic heterogeneity. Additionally, we identified a multi-layered epigenetic axis centered on RTN4IP1, where hypermethylation is genetically associated with reduced systemic expression and protein abundance. However, tissue-specific and GEO analyses revealed a paradoxical localized upregulation of RTN4IP1 in diseased atrial myocardium, suggesting a complex, tissue-specific regulatory mechanism. Finally, PPI network analysis demonstrated that these prioritized candidate genes are directly connected to mitochondrial master regulators and OXPHOS complexes. CONCLUSIONS:Our study prioritizes specific mitochondrial genes associated with MVD, identifying PCCB as the most consistent candidate risk gene supported by systemic and localized tissue evidence.

This study evaluated the safety and efficacy of the Renatus transcatheter aortic valve system in treating severe aortic stenosis. This prospective, multicenter, single-arm clinical trial employed a target-value approach. The primary endpoint was the all-cause mortality rate at one year postoperatively, while secondary endpoints included assessments of safety and effectiveness. Safety was measured by the all-cause mortality rate at 30 days, the incidence of major adverse cardiovascular events within one year, and the device success rate. Effectiveness was assessed using transvalvular pressure gradient measurements, the incidence of paravalvular leaks, improvements in New York Heart Association (NYHA) cardiac function classification, and quality of life assessments. The study enrolled 166 patients across 14 national centers between July 2021 and April 2022, with a mean age of 73.9 ± 6.0 years and a median STS risk score of 7.7