Daily Cardiology Research Analysis

BACKGROUND: The SELECT trial found semaglutide reduced major adverse cardiovascular events (MACE) in patients with overweight or obesity with cardiovascular disease but without diabetes. We report a prespecified analysis of the SELECT trial on the relationships between baseline adiposity measures, treatment-induced adiposity changes, and subsequent MACE risk. METHODS: Patients aged at least 45 years, with a BMI of at least 27 kg/m FINDINGS: Semaglutide significantly reduced MACE incidence compared with placebo among 17 604 patients enrolled in SELECT, with consistent benefits across all baseline weight and waist circumference categories. In the semaglutide group, analyses for linear trends showed lower baseline bodyweight and waist circumference were associated with lower incidence of MACE-an average 4% reduction in risk per 5 kg lower bodyweight (hazard ratio [HR] 0·96 [95% CI 0·94-0·99]; p=0·001) and per 5 cm smaller waist circumference (0·96 [0·93-0·99]; p=0·004). In the placebo group, lower baseline waist circumference (0·96 [0·94-0·99]; p=0·007), but not bodyweight (0·99 [0·97-1·01]; p=0·28), was associated with a lower MACE risk and weight loss was paradoxically associated with increased MACE risk. In those receiving semaglutide there was no linear trend linking weight loss at week 20 to subsequent MACE risk, but greater waist circumference reduction at week 20 was associated with lower subsequent MACE risk, and waist circumference reduction by week 104 was associated with lower in-trial risk of MACE. An estimated 33% of the observed benefit on MACE was mediated through waist circumference reduction (HR 0·86 [95% CI 0·77-0·97] after adjustment for time-varying changes in waist circumference). INTERPRETATION: The cardioprotective effects of semaglutide were independent of baseline adiposity and weight loss and had only a small association with waist circumference, suggesting some mechanisms for benefit beyond adiposity reduction. FUNDING: Novo Nordisk.

BACKGROUND: Ablation procedures for atrial fibrillation (AF), including catheter (CA) and surgical ablation, are effective rhythm control therapies. This study is a Bayesian network meta-analysis evaluating randomised evidence on the invasive treatment of AF, focusing on freedom from atrial tachyarrhythmias (ATAs) while evaluating the potential trade-off in morbidity and mortality. METHODS: This study was registered in PROSPERO (CRD42025632171). Randomised controlled trials (RCTs) were included comparing any of the 4 treatments; CA, isolated thoracoscopic, hybrid thoracoscopic ablation, and the Convergent procedure. Primary outcome was freedom from ATA at 12 months. Secondary outcomes were mortality, stroke, and bleeding. A Bayesian-network meta-analysis was performed. The combined effects of the primary and secondary outcomes were studied in a bivariate analysis. Treatments were ranked and their effects were summarised using surface under the cumulative ranking curves (SUCRAs). RESULTS: Ten RCTs were included in the analysis (n = 877 patients, predominantly persistent AF). Using CA as a reference, the pooled network odds ratios for freedom from ATA for hybrid thoracoscopic, isolated thoracoscopic, and Convergent were 4.95 (95% credible interval [CrI] 2.16-13.46), 2.23 (95% CrI 1.23-4.48), and 2.23 (95% CrI 0.90-6.69), with SUCRAs for hybrid thoracoscopic, isolated thoracoscopic, Convergent, and CA of 95.5%, 50.8%, 52.1%, and 1.5%, respectively. No increase in periprocedural morbidity or mortality was observed. Results were robust across various sensitivity analyses. CONCLUSIONS: In this Bayesian-network meta-analysis consisting exclusively of randomised data, surgical ablation in general and hybrid ablation in particular provide superior outcome in terms of 1-year freedom from ATA. Both CA and surgical procedures are characterised by a favourable safety profile.

Mechanical forces play a critical role in heart development by activating mechanotransduction pathways. However, applying forces to cardiac organoid models has significant challenges due to technical limitations. In this study, we applied mechanical forces to cardiac organoids with a magnetic torque stimulation (MTS) system using magnetized nanoparticles controlled by a magnetic levitation system. Torque was exerted on developing cardiac organoids within a uniform magnetic field generated by a rotating magnet system. Cardiac organoids exposed to torque showed spatial distribution of atrial and ventricle specific marker proteins such as MLC2v and MLC2a. Gene expression analysis revealed that torque-applied organoids exhibited upregulation of maturation-related genes such as TNNT2, GJA1, MYH7, and KCNJ2 as well as vascular specific genes such as PECAM1, VWF, PDGFRB, and ACTA2. Analysis of mechanotransduction-related genes and proteins indicated increased expression of Lamin A/C, ITGA5, ITGB3, and emerin. Elevated phosphorylation levels of FAK, cofilin, and MLC2 were also confirmed in response to the applied force. Our findings suggest that mechanical force application via MTS system can promote both maturation and vascularization of cardiac organoids by activating mechanotransduction pathways. STATEMENT OF SIGNIFICANCE: Mechanical cues are key regulators of cardiac development, yet their role in organoid maturation remains underexplored. In this study, we introduce a Magnetic Torque Stimulation (MTS) system that delivers precisely controlled rotational forces to stem cell-derived cardiac organoids via surface-bound magnetic particles. Application of MTS significantly promoted cardiac differentiation, structural maturation, and neovascularization within the organoids in vitro. These effects are attributed to mechanotransductive modulation of key developmental signaling pathways. The MTS platform offers a robust strategy for investigating biomechanical regulation of cardiac organogenesis and holds translational potential for organoid-based disease modeling, drug discovery, and regenerative medicine.