Understanding the severity and anatomical pattern of coronary artery disease (CAD), particularly whether lesions are focal or diffuse, is critical in determining the most effective treatment strategy for patients with significant left anterior descending (LAD) disease. Although percutaneous coronary intervention remains the preferred treatment for focal disease, diffuse CAD presents therapeutic challenges, with options ranging from optimal medical therapy to coronary artery bypass grafting. The COMMIT LAD registry is a prospective, multicenter observational study initiated in the Netherlands in January 2024, enrolling patients with symptomatic and significant LAD disease. The registry collects longitudinal data at multiple follow-up points over 12 months. The primary aim was to assess the 1-year incidence of major adverse cardiovascular events, including cardiovascular death, myocardial infarction, stroke, or unplanned revascularization, in patients receiving either surgical or pharmacological treatment for diffuse LAD disease. Key secondary endpoints include patient-reported symptom burden and quality of life, assessed using validated questionnaires. This study provides a real-world overview of current treatment approaches to LAD disease, emphasizing differences in outcomes between diffuse and focal CAD. Despite limitations such as nonrandomized design and variability in treatment selection, COMMIT LAD offers valuable insights into practice patterns and patient experiences across centers. Findings from this registry are expected to inform clinicians about comparative outcomes and guide more tailored treatment strategies for diffuse CAD.

Mechanical heart valve replacement necessitates long-term warfarin anticoagulation to prevent thromboembolic complications, yet achieving adequate anticoagulation control remains challenging. This study evaluated whether mean platelet volume (MPV) could serve as a biomarker for anticoagulation quality in mechanical heart valve recipients. We conducted a retrospective longitudinal cohort analysis of 370 patients with mechanical heart valves receiving warfarin therapy. MPV and international normalized ratio (INR) were measured at five time points. Time in therapeutic range (TTR) was calculated using the Rosendaal method, with effective anticoagulation defined as TTR ≥60%. Correlations between MPV, INR, and TTR were analyzed overall and stratified by valve type. Only 34.1% of patients achieved effective TTR. Mean MPV was 10.31 ± 1.04 fL and mean INR was 2.79 ± 0.54. No significant correlation was identified between MPV and TTR. However, patients with mean INR ≤3.0 exhibited significantly higher MPV values compared to those with INR >3.0 (10.40 vs 10.13 fL). Subgroup analysis revealed a significant inverse correlation between MPV and INR in mitral valve replacement patients but not in aortic valve replacement patients, with temporal variation across measurement periods. MPV showed poor discriminatory ability for predicting effective TTR. Multivariable regression identified atrial fibrillation, older age, higher platelet counts, and higher hemoglobin as independent predictors of effective TTR, while MPV showed no independent association. In conclusion, MPV does not serve as a reliable biomarker for anticoagulation quality in mechanical heart valve patients. Enhanced anticoagulation management strategies are needed to improve TTR in this high-risk population.

The aim of this study was to evaluate real-world rivaroxaban safety and adherence in patients with nonvalvular atrial fibrillation (NVAF). A prospective, observational, cohort, postmarketing study was conducted during a six-month period. The primary outcome was bleeding, including major bleeding, non-major bleeding, and fecal occult blood test positivity. Secondary outcomes included non-bleeding adverse reactions, changes in laboratory parameters, and therapy adherence measured by the Morisky Medication Adherence Scale-8 (MMAS-8). We included 1184 patients evaluated at baseline and at one, three, and six months. During follow-up, cumulative incidences (95% confidence interval) were 0.9% (0.5-1.7%) for major bleeding, 13.3% (11.4-15.3%) for non-major bleeding, and 3.4% (2.4-4.6%) for fecal occult blood positivity. Other adverse drug reactions were infrequent and mild, most commonly headache and fatigue, and no clinically relevant deterioration of laboratory parameters was observed. MMAS-8 score was the same throughout the follow-up period and was 1.0 (interquartile range 0.0-2.0), which is in the domain of good therapy adherence. Approximately one-third of patients demonstrated full therapy adherence, and one-fifth of patients exhibited poor adherence. This real-world study supports the favorable safety profile and generally good patient adherence to rivaroxaban in NVAF, though continued monitoring of bleeding risk and enhanced patient education on adherence remain crucial for optimal outcomes.

Atrial fibrillation (AF) is the most common arrhythmia leading to cardioembolic stroke, with inflammation of epicardial adipose tissue (EAT) contributing to its pathogenesis. However, current therapies cannot specifically target EAT inflammation to alleviate AF. This study investigated the effects of sonodynamic therapy (SDT) on reducing macrophage-mediated inflammation in the EAT of rabbit AF models and explored its potential clinical application in AF patients. Rabbits were assigned to sham, paced (600 bpm for 4 w), and SDT groups. Macrophage infiltration and collagen deposition were evaluated using RAM11 immunohistochemistry and Masson staining, respectively. Transcriptomic analysis and network pharmacology identified TLR4/NF-κB pathway genes (including CXCL8 and CCL2) as SDT targets for AF treatment, which were validated by Western blot and RT-qPCR. Single-cell sequencing of human EAT and right atrial appendage confirmed the expression of these SDT-targeted genes in macrophages from AF patients. Mendelian randomization demonstrated that elevated plasma CXCL8, but not CCL2, was associated with an increased risk of atrial fibrillation. SDT reduced macrophage infiltration, fibrosis, and TLR4/NF-κB-mediated inflammation, supporting its therapeutic potential in AF via modulation of EAT inflammation.

Pulmonary hypertension (PH) causes right heart failure (RHF), leading to an unfavorable prognosis. This prospective single-arm study evaluated the acute effects of levosimendan in 105 patients with RHF secondary to PH. Levosimendan was administered as a continuous infusion at 0.1 μg/kg/min over 24 h. The primary endpoint was improvement in WHO Functional Class (WHO-FC) at day 7, with secondary endpoints including Borg dyspnea scores, systolic pulmonary artery pressure (SPAP), and echocardiographic parameters. Treatment resulted in significant clinical and hemodynamic improvements by day 7. WHO-FC decreased from a median of 4.00 (3.00, 4.00) to 3.00 (2.00, 3.00) ( P < 0.001), and Borg dyspnea scores improved from 8.00 (6.00, 8.00) to 4.00 (4.00, 5.00) (P < 0.001). SPAP decreased significantly from 57.51 (51.24, 68.00) mmHg to 50.16 (44.55, 59.83) mmHg ( P = 0.002). Echocardiography showed favorable changes, including reduced left ventricular end-systolic volume and tricuspid regurgitation velocity, alongside increased left ventricular fractional shortening. In a subgroup with left heart disease, left ventricular ejection fraction increased from 33.10 (27.58, 47.20) % to 36.50 (30.63, 49.50) % ( P = 0.025). Patients with heart failure with preserved ejection fraction also showed reduced SPAP and tricuspid regurgitation velocity. The findings suggest that levosimendan provides acute physiological benefits in PH-related RHF, with potential anti-inflammatory, hepatoprotective, and glycemic-modulating properties. Patient-specific medical history and concomitant medications may influence treatment response. This study offers preliminary evidence supporting the acute physiological effects and tolerability of levosimendan in this population.

Injectable PCSK9 inhibitors effectively lower LDL-C levels in patients with hypercholesterolemia; however, their high cost and requirement for parenteral administration limit their widespread use. Oral PCSK9 inhibitors have emerged as a convenient alternative. This review and meta-analysis of the literature evaluate the effectiveness and safety of oral PCSK9 inhibitor treatment for adults with hypercholesterolemia. PubMed, Embase, Cochrane CENTRAL, and Scopus were searched through September 2025 for randomized controlled trials comparing oral PCSK9 inhibitors with placebo. The primary outcome was percentage change in LDL-C, with secondary lipid and safety outcomes. We used Cochrane RoB 2.0 tool to assess risk of bias, and pooled estimates were calculated using a random-effects model. Certainty of evidence was evaluated with GRADE. From 1253 records, 3 trials were included. Participants were mostly men, aged 61-65 years, with elevated baseline LDL-C. Oral PCSK9 inhibitors significantly reduced LDL-C and ApoB in a dose-dependent manner and achieved modest reductions in triglycerides (MD -6.56 mg/dL; 95% CI, -12.30 to -0.83) and total cholesterol (MD -25.25 mg/dL; 95% CI, -30.67 to -19.83). Effects on lipoprotein(a) were inconsistent. Adverse events (RR 1.06; 95% CI, 0.91-1.23) and serious adverse events (RR 1.32; 95% CI, 0.41-4.26) were comparable with placebo. According to our review, oral PCSK9 inhibitors are a promising therapeutic option for treating hypercholesterolemia because of their potent lipid-lowering effects and an overall favorable safety profile. However, more trials are needed to confirm their impact on cardiovascular outcomes.

Aspirin (ASA) is the cornerstone of the acute coronary syndrome primary and secondary prevention. Still, its role is debated in some high bleeding risk patients or cases that underwent second-generation drug-eluting stents with a better scaffold. This study compared the efficacy and safety of aspirin-free versus aspirin-based strategies in patients with ACS undergoing PCI. We systematically searched PubMed, Embase, Scopus, and ScienceDirect for studies comparing aspirin-based versus aspirin-free strategies in patients with ACS undergoing PCI. Pooled relative risk (RR) with 95% CI was calculated using a fixed effects model or a random effects model if heterogeneity was present. Significance was set at P < 0.05. Thirty studies including 207,938 patients (N = 104,062 in the ASA arm, and 103,876 in the ASA-free arm) were included in this study. There was a statistically significant reduction in risk of all-cause mortality [RR 0.93, 95% CI, 0.87-0.99, P-value = 0.024, I2 = 0%], BARC 2-5 [RR = 0.68, 95% CI, 0.58-0.81, P-value = <0.01, I2 = 0%], BARC 3 or 5 [RR= 0.71, 95% CI, 0.60-0.82, P-value= <0.01, I2 = 0%], TIMI major bleeding [RR = 0.66, 95% CI, 0.50-0.86, P-value= 0.02, I2 = 0%], TIMI minor or major bleeding [RR= 0.61, 95% CI, 0.52-0.72, P-value= <0.01, I2 = 0%], and ISTH major bleeding with aspirin-free strategy [RR= 0.52, 95% CI, 0.42-0.64, P-value= <0.001, I2= 0%]. Other secondary outcomes showed statistically nonsignificant results. The aspirin-free strategy showed lower all-cause mortality and bleeding, supporting its efficacy and safety in high bleeding risk patients.

Myocardial ischemia-reperfusion (I/R) injury remains a major cause of acute cardiac dysfunction and is characterized by oxidative stress, inflammation, and apoptosis. Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has been reported to exert cardioprotective effects; however, its potential association with mitochondrial biogenesis-related signaling pathways remains incompletely understood. The aim of this study was to evaluate the cardioprotective potential of CBD in a rat myocardial I/R model and to investigate its possible association with SIRT-1/PGC-1α-related mitochondrial biogenesis and nuclear factor kappa B (NF-κB)-dependent inflammatory signaling. Forty rats were randomly assigned to 4 groups: sham, I/R, prophylactic CBD, and therapeutic CBD. Myocardial ischemia was induced by ligating the left anterior descending coronary artery for 30 minutes, followed by 30 minutes of reperfusion. Heart and aortic tissues were evaluated histopathologically, immunohistochemically, biochemically, and genetically to assess oxidative stress, inflammation, and mitochondrial biogenesis-related markers. The I/R group exhibited marked myocardial injury characterized by hyperemia, edema, hemorrhage, and inflammatory infiltration, accompanied by elevated levels of vascular cell adhesion molecule-1 (VCAM-1), vascular endothelial growth factor, and NF-κB. By contrast, SIRT-1, PGC-1α, and B-cell lymphoma 2 (Bcl-2) expression significantly declined, alongside increased total oxidant status and oxidative stress index. Prophylactic CBD treatment notably restored myocardial architecture, suppressed inflammatory and apoptotic responses, and enhanced mitochondrial biogenesis. Therapeutic CBD administration also provided partial protection. CBD confers robust cardioprotection against myocardial I/R injury by activating the SIRT-1/PGC-1α axis, promoting mitochondrial biogenesis, and attenuating oxidative, inflammatory, and apoptotic pathways. These findings indicated that it confers significant cardioprotection against myocardial IR injury and that this protective effect is associated with modulation of SIRT-1/PGC-1α-related mitochondrial biogenesis and NF-κB-dependent inflammatory signaling. Further mechanistic studies are warranted to establish definitive causal relationships.

Heart failure (HF) represents a significant global public health challenge with profound implications for human health. Shenfu Xiangshao Decoction (SFXSD) is a commonly used adjuvant therapy for HF. However, its molecular mechanism remains unclear. This study aims to explore the core components, key targets, and potential mechanisms of SFXSD in the treatment of HF. Network pharmacology, molecular docking, and molecular dynamics simulations were used to identify the active compounds and targets of SFXSD. A 3D HF cardiac organoid model was developed using doxorubicin (DOX). Techniques such as Western blotting, TUNEL staining, ELISA, and Masson staining were performed to investigate the mechanisms of SFXSD. SFXSD acted on HF, comprising 126 active ingredients and 33 core cross-targets. The 4 principal effector components, quercetin, kaempferol, licochalcone A, and naringenin, could form stable complexes with the core target MAPK14 (p38 MAPK). In this study, we successfully constructed an HF cardiac organoid model using 10 μM DOX, on which the mechanism was validated. The results indicated that quercetin and kaempferol, the active ingredients of SFXSD, could ameliorate DOX-induced cardiac organoids apoptosis, inflammation, and fibrosis by reducing the expression of p38/ERK MAPK, BAX/BCL-2 ratio, the release of TNF-α, and IL-6. This in vitro 3D cardiac organoid model provides a valuable platform for drug screening and disease modeling, while the discovery of quercetin and kaempferol offers a solid theoretical basis for HF treatment.