Cardiovascular Therapeutics最新文献

Aims

Novel drugs that target apoC-III in lipoprotein metabolism to reduce plasma triglycerides are currently under development. Olezarsen, a drug similar to its predecessor, volanesorsen, is in Phase 3 trials. A meta-analysis of RCTs was done to study its effect on hypertriglyceridemia.

Material and Methods

Screening was done on PubMed, Embase, Scopus, and the Cochrane Library from inception to August 2024. We used Review Manager (Version 5.4) for statistical analysis. Subgroups of olezarsen at doses of 10, 50, and 80 mg were made. Continuous outcomes were reported as mean differences with 95% CIs. Adverse events were reported using risk ratios and 95% CIs. The risk of bias was analyzed using the Cochrane risk of bias tool.

Results

Four RCTs with 374 participants, 278 in intervention and 96 placebo controls, were included. At all doses of olezarsen, a significant reduction in fasting triglyceride levels (MD: 45.69; 95% CI: 35.84, 55.54; p < 0.00001) was seen. This was most pronounced at 80 mg dose (MD: 51.98 95% CI: 43.06, 60.90; p < 0.00001). A reduction in apoC-III (MD: 58.77; 95% CI: 35.94, 81.61; p < 0.00001) and an increase in HDL (MD: 0.21; 95% CI: 0.04, 0.37; p = 0.01) were also observed. No significant effect was observed on LDL levels (MD: −0.13; 95% CI: −0.40, 0.14; p = 0.34). Overall, no significant adverse effects were seen compared to placebo (RR: 1.42; 95% CI: 0.66, 3.05; p = 0.37).

Conclusion

Olezarsen showed remarkable efficacy in lowering triglycerides, with a dose-dependent effect, while significantly increasing HDL levels and reducing apoC-III. Its safety profile is commendable. Although it performed well compared to volanesorsen, inconsistencies in LDL reduction and heterogeneity in some groups warrant further large-scale RCTs to better assess its safety and efficacy. Clinical decisions should be tailored to individual patient profiles, as hypertriglyceridemia management may vary on a case-to-case basis.

Aims

To evaluate the real-world efficacy and safety of low-dose (2.5 mg) mavacamten initiation in Chinese patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).

Methods and Results

This single-center observational study (Zhongshan Hospital, China; Oct 2024–Apr 2025) enrolled 72 symptomatic oHCM patients (NYHA II/III, LVEF ≥ 55%, resting/Valsalva-provoked LVOT gradient [LVOTG] ≥ 30 mmHg). All patients initiated mavacamten 2.5 mg once daily. Doses were adjusted at Weeks 4, 8, and 12 based on LVEF and LVOTG. Primary outcomes were changes in resting/provoked LVOTG, NT-proBNP, and NYHA class at Week 12. Safety outcomes included LVEF < 50%, cardiac hospitalization, and death.

Significant reductions from baseline to Week 12 were observed: Resting LVOTG (52.4 ± 28.7 to 32.1 ± 23.1 mmHg, p < 0.001), Valsalva-provoked LVOTG (74.1 ± 24.4 to 48.7 ± 25.4 mmHg, p < 0.001), NT-proBNP (1102.7 ± 1114.9 to 320.2 ± 406.2 pg/mL, p < 0.001). LVEF remained stable. NYHA class improved by ≥ 1 class in 83.3% (60/72) of patients.

Subgroup analyses revealed significantly greater LVOTG reductions in patients with classic HCM (vs. apical HCM, p < 0.001) and high baseline resting LVOTG (≥ 50 mmHg vs. < 50 mmHg, p < 0.001/p = 0.04). NYHA improvement was consistent across subgroups.

Twenty-two patients escalated to 5 mg at Week 12, achieving further significant LVOTG reductions (p < 0.001), particularly in apical HCM and high-baseline-gradient subgroups, with stable LVEF.

No safety events occurred (LVEF < 50%, arrhythmias, hospitalization, and death). Four patients reported transient minor adverse events (dizziness, nausea, and fatigue).

Conclusion

In this first Chinese real-world study, initiating mavacamten at 2.5 mg significantly improved haemodynamics (LVOTG), biomarkers (NT-proBNP), and functional status (NYHA) in oHCM patients over 12 weeks with an excellent safety profile. Greater haemodynamic efficacy was observed in classic HCM and high-baseline-gradient patients. Escalation to 5 mg provided additional benefit. Mavacamten is an effective and safe therapy for oHCM in this Asian population.

Background

The relationship between hypothyroidism and cardiovascular disease is well established. However, data on subclinical hypothyroidism (SH) and its impact on major adverse cardiovascular events (MACEs) and postoperative complications following coronary artery bypass grafting (CABG) remain limited. This study was aimed at evaluating whether SH is associated with an increased risk of these outcomes.

Methods

From 2010 to 2019, 863 patients who underwent CABG for cardiovascular diseases at a reference center were included. The primary outcomes included MACE (composite and individual events: all-cause death, cardiovascular death, stroke, acute myocardial infarction [AMI], and new revascularization) and postoperative complications, including atrial fibrillation (AF), pleural effusion (PLE), pericardial effusion (PCE), infections at any site (IASs), and mediastinitis.

Results

SH patients had higher rates of MACE (20.3% vs. 8.2%, p = 0.001), MACE 4p (22.0% vs. 12.9%, p = 0.002), and stroke (10.2% vs. 3.0%, p = 0.013) than those of euthyroid patients. No significant differences were observed in all-cause death, cardiovascular death, AMI, or new revascularization. Postoperative complications were also more frequent in the SH group: AF (18.6% vs. 9.7%, p = 0.043), PLE (52.6% vs. 19.2%, p < 0.0001), PCE (20.3% vs. 7.8%, p = 0.03), and IAS (28.8% vs. 16.9%, p = 0.032). However, no significant difference was noted in the incidence of mediastinitis.

Conclusions

SH patients who underwent CABG had a higher frequency of MACE and postoperative complications than those of euthyroid patients.

Background

Coronary heart disease (CHD) is a leading cause of cardiovascular mortality worldwide, with its pathogenesis being complex and not yet fully understood. The rapid development of genomics, especially in epigenetic research, has provided essential tools for identifying new pathogenic targets. This study is aimed at systematically exploring the molecular mechanisms of CHD using protein quantitative trait locus (pQTL) data and multiomics Mendelian randomization (MR) approaches, with a specific focus on the epigenetic regulation of the key gene ITGB7.

Methods

The study first integrated 1812 cis-pQTL data with CHD GWAS data to perform a two-sample MR analysis, identifying protein-coding genes significantly associated with CHD. Transcriptomic data were then used to validate the differential expression of these genes. Subsequently, a two-step MR mediation analysis was conducted to explore the upstream regulatory effect of DNA methylation on the key gene ITGB7, as well as the potential mediating roles of ITGB7 on downstream immune cells and plasma metabolites.

Results

MR analysis identified 17 genes significantly positively associated with CHD, with PCSK9 and ITGB7 showing significant upregulation in the peripheral blood of CHD patients. Mediation analysis revealed that the DNA methylation site cg14524975 (beta_p = 45.64%) significantly increased the risk of CHD by positively regulating the expression of ITGB7. In downstream mechanisms, ITGB7 significantly promoted CHD progression by regulating immune cells, such as CD4+ CD8dim AC (beta_p = 12.04%), and plasma metabolites, including N,N-dimethylalanine (beta_p = 18.96%), benzoate-to-oleoyl–linoleoyl–glycerol (18:1 to 18:2) ratio (beta_p = 34.63%), and serine-to-threonine ratio (beta_p = 12.58%).

Conclusion

This study identifies ITGB7 as a novel pathogenic gene for CHD and reveals its multiomics mechanisms in promoting CHD development through DNA methylation regulation, immune response activation, and metabolic pathway disruption. The findings provide valuable theoretical insights and potential biomarkers for the pathogenesis and targeted intervention of CHD.

Background

Elderly patients with heart disease face elevated mortality risk, yet predictive models specifically tailored for this population across different global regions remain limited. Current mortality prediction tools often lack cross-cultural validation and interpretability, hindering their clinical application in diverse healthcare settings.

Methods

We developed and validated machine learning models for predicting mortality in elderly heart disease patients using data from three major aging cohorts: the China Health and Retirement Longitudinal Study (CHARLS, n = 2130), the Survey of Health, Ageing and Retirement in Europe (SHARE, n = 10,928), and the Health and Retirement Study (HRS) from the United States (n = 4835). Boruta feature selection identified 27 common predictors across cohorts. Eleven machine learning algorithms were trained on the SHARE cohort (70% training and 30% testing) and externally validated on CHARLS and HRS cohorts. Model performance was assessed using area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and calibration metrics. SHapley Additive exPlanations (SHAP) analysis was employed to interpret model predictions.

Results

XGBoost demonstrated superior performance with the highest average AUC (0.798) across all datasets, showing excellent generalizability from the SHARE training set (AUC: 0.805) to internal validation (AUC: 0.799) and external validation in HRS (AUC: 0.821) and CHARLS (AUC: 0.770) cohorts. Age consistently emerged as the most influential predictor across all cohorts (SHAP values: 0.056–0.102), followed by gender, moderate physical activity, and self-rated health, though their relative importance varied by cohort. Feature dependence analysis revealed important nonlinear relationships, including U-shaped associations between grip strength and mortality risk.

Conclusion

Our multicohort machine learning approach successfully developed a robust, interpretable model for predicting mortality in elderly heart disease patients across diverse global populations. The model′s strong performance in external validation demonstrates its potential for cross-cultural clinical application, while SHAP analysis provides valuable insights into population-specific risk factors that could guide targeted interventions.

Background

Drug-coated balloons (DCBs) present a viable option distinct from drug-eluting stents (DESs) in addressing coronary artery disease (CAD), particularly when it comes to in-stent restenosis (ISR) scenarios. The utilization of DCBs marks a significant deviation from traditional DES applications. For CAD patients experiencing ISR, DCBs offer an innovative pathway to treatment. However, their efficacy and safety in de novo CAD lesions remain uncertain. This meta-analysis evaluates DCB versus other percutaneous coronary intervention (PCI) strategies, including DES, bare-metal stents (BMSs), and plain old balloon angioplasty (POBA), in de novo CAD.

Methods

A comprehensive search was conducted across PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL), spanning from their inception up until November 14, 2024. Studies included were randomized controlled trials (RCTs) and cohort studies, which assessed DCB against alternative PCI strategies in patients with de novo CAD. The key outcome measures focused on major adverse cardiac events (MACEs) as well as late lumen loss (LLL). Trial sequential analysis (TSA) assessed the robustness of findings.

Results

Fifty studies (19 RCTs, 31 cohort studies) involving 28,292 patients were analyzed. DCB showed a lower MACE incidence compared to noncoated devices (RR = 0.52, 95% CI: 0.40–0.69) but no significant difference versus DES (RR = 0.96, 95% CI: 0.84–1.10). DCB significantly reduced LLL compared to all controls (MD = −0.22, 95% CI: −0.29 to −0.14). Subgroup analyses confirmed DCB′s safety across indications, ethnicities, comorbidities, and dual antiplatelet therapy (DAPT) durations, with reduced LLL in small vessel disease and shorter DAPT. TSA supported LLL findings but indicated inconclusive MACE results in RCTs, necessitating further research.

Conclusion

DCB is a safe and effective alternative to DES in de novo CAD, with comparable safety and superior LLL reduction. However, MACE results in RCTs require further validation. Future studies should explore long-term outcomes and integrate newer-generation DCB and DES technologies to optimize clinical practice.

Purpose

To explore the relationship between the Naples Score and the recurrence of atrial fibrillation (AF) following radiofrequency catheter ablation (RFCA) in patients.

Methods

We conducted a retrospective analysis of 719 patients with AF who underwent radiofrequency catheter RFCA between April 2019 and October 2024 at Yantai Yuhuangding Hospital of Qingdao University. We utilized Cox multifactorial regression analysis and Kaplan–Meier survival curves to evaluate the relationship between the Naples Score and the recurrence of AF following RFCA. Additionally, a receiver operating characteristic (ROC) curve was generated to assess the predictive value of the Naples Score for recurrence.

Results

After follow-up, 156 (21.7%) AF patients occurred recurrence. A significant difference in recurrence rates was observed among patients with varying Naples Scores (14.0% vs. 20.8% vs. 34.2%, p < 0.001). The Cox multifactorial regression analysis indicated that the Naples Score was an independent risk factor for recurrence following RFCA of AF (hazard ratio [HR] = 1.28, p < 0.001). The postoperative recurrence rate was significantly higher in patients with elevated Naples Scores compared with those with lower scores (HR = 2.25, p < 0.001). Kaplan–Meier survival analysis revealed significant differences in recurrence rates among patients with different Naples Scores (Log − rank p < 0.001). ROC curve analysis demonstrated the predictive value of the Naples Score for recurrence after RFCA in AF, with an AUC of 0.62 (95% confidence interval [CI]: 0.57–0.66, p < 0.001).

Conclusion

Naples Score was identified as an independent risk factor for recurrence following RFCA of AF.

Background

The 2024 European Society of Cardiology (ESC) guideline newly recommended clopidogrel as a safe and effective alternative to aspirin monotherapy in patients with chronic coronary disease (CAD). We aimed to validate the 2024 ESC guideline recommendation by comparing the prognosis of patients with chronic CAD treated with P2Y12 inhibitor monotherapy and aspirin monotherapy.

Methods

This retrospective cohort study included patients with chronic CAD (18 months after percutaneous coronary intervention [PCI] with drug-eluting stents [DES] in 2019–2023), based on a nationwide health claims database in Korea. A 1:1 propensity score matching was performed between P2Y12 inhibitors and aspirin monotherapy groups. The primary composite outcome included all-cause death, myocardial infarction, ischemic stroke, and major bleeding. Stratified Cox regression models were used to compare risks between groups.

Results

Of 127,127 patients with chronic CAD (mean age: 63.1 years; 73.7% men), 84,440 (66.4%) patients received P2Y12 inhibitor monotherapy, and 42,727 (33.6%) received aspirin monotherapy. After propensity score matching, 42,692 pairs were generated. During a median follow-up of 3 years, P2Y12 inhibitor monotherapy did not reduce the risk of the primary composite outcome (hazard ratio [HR]: 0.98; 95% confidence interval [CI]: 0.92–1.05; p = 0.577) compared with aspirin monotherapy. In secondary analyses, P2Y12 inhibitors showed a trend toward reduced major bleeding (HR: 0.86; 95% CI: 0.72–1.02; p = 0.082) and a significant reduction in major gastrointestinal bleeding (HR: 0.79; 95% CI: 0.63–0.97; p = 0.027).

Conclusions

Among Korean patients with chronic CAD in the long-term maintenance period after PCI using DES, P2Y12 inhibitor monotherapy demonstrated overall outcomes comparable with aspirin monotherapy, with a potential advantage in reducing bleeding, particularly of gastrointestinal origin. These findings support the safety and feasibility of P2Y12 inhibitor monotherapy, in line with the 2024 ESC guideline recommendations, while emphasizing the need for further prospective studies to confirm its clinical benefit.

Objective

Hyperhomocysteinemia is a risk factor for cardiovascular disease, but its impact on valve disease is lacking in research. This study was aimed at investigating the impact of hyperhomocysteinemia on rheumatic mitral valve calcification and prognosis in patients undergoing surgery.

Methods

This study included 672 patients with severe rheumatic mitral valve stenosis who underwent surgery between January 2016 and December 2022. Patients were stratified by preoperative homocysteine levels. Mitral valve pathology was assessed by echocardiography and coronary CTA, with all-cause mortality as the primary mid-term endpoint.

Results

Among this surgical cohort of 672 patients with severe rheumatic mitral stenosis, 208 (31.0%) patients were identified with hyperhomocysteinemia. Imaging assessment revealed that these patients had a higher Agatston score for mitral valve calcification (37.47 vs. 17.19, p = 0.038) after adjusting baseline data. Restricted cubic splines revealed a significant dose–response relationship, with mitral valve calcification increasing progressively with higher homocysteine levels (p < 0.001). The Kaplan–Meier survival analysis showed that patients with hyperhomocysteinemia had significantly lower mid-term survival rates (log-rank p = 0.004). Through univariate and multivariate COX regression analyses, it was found that hyperhomocysteinemia was an independent risk factor affecting mid-term postoperative survival (HR, 2.257; p = 0.048).

Conclusions

In patients undergoing surgery for rheumatic heart disease, hyperhomocysteinemia was associated with the formation of rheumatic mitral valve calcification and increased mid-term postoperative mortality.

Trial Registration: Chinese Clinical Trial Registry identifier ChiCTR2200067151