Endothelial dysfunction (ED) is characterized by imbalanced vasodilation and vasoconstriction, elevated reactive oxygen species (ROS), and inflammatory factors, as well as deficiency of nitric oxide (NO) bioavailability. It has been reported that the maintenance of endothelial cell integrity serves a significant role in human health and disease due to the involvement of the endothelium in several processes, such as regulation of vascular tone, regulation of hemostasis and thrombosis, cell adhesion, smooth muscle cell proliferation, and vascular inflammation. Inflammatory modulators/biomarkers, such as IL-1α, IL-1β, IL-6, IL-12, IL-15, IL-18, and tumor necrosis factor α, or alternative anti-inflammatory cytokine IL-10, and adhesion molecules (ICAM-1, VCAM-1), involved in atherosclerosis progression have been shown to predict cardiovascular diseases. Furthermore, several signaling pathways, such as NLRP3 inflammasome, that are associated with the inflammatory response and the disrupted H2S bioavailability are postulated to be new indicators for endothelial cell inflammation and its associated endothelial dysfunction. In this review, we summarize the knowledge of a plethora of reviews, research articles, and clinical trials concerning the key inflammatory modulators and signaling pathways in atherosclerosis due to endothelial dysfunction.

Mitral regurgitation (MR) is a prevalent and prognostically relevant valvular disease, especially in patients with heart failure, in whom MR contributes to adverse remodeling, increased symptom burden, and higher mortality. Surgical repair or replacement remains the standard of care for suitable candidates, but many patients are excluded because of advanced age, comorbidities, or high surgical risk. Transcatheter methods have emerged as transformative alternatives, including mitral transcatheter edge-to-edge repair (MTEER) with devices such as MitraClip and PASCAL, annuloplasty-based devices such as Carillon and Cardioband, and transcatheter mitral valve replacement (TMVR) with devices such as Tendyne, Intrepid, and others under development. Data from randomized trials and registries have established that MTEER lowers hospital readmission rates and improves mortality in carefully selected secondary MR subjects, and that device upgrades improve procedural success and anatomical versatility. Annuloplasty provides targeted repair for functional MR with annular dilation, whereas TMVR offers an alternative for anatomically complex cases or those ineligible for MTEER, albeit with distinct procedural risks. Management of severe mitral annular calcification remains difficult and demands meticulous pre-procedural planning and customized device strategies. Careful patient selection based on MR etiology, proportionality, ventricular function, and anatomical suitability is essential for optimizing outcomes in this rapidly evolving field.

Background/Introduction: The clinical importance of a hypertensive response to exercise (HRE) in subjects with high normal blood pressure (BP) is not fully elucidated, while sympathetic overactivity followed by arterial stiffening are linked with development of hypertension. Purpose: The aim of this study was to assess parameters related to the development of hypertension in a 3 year follow in subjects with high normal BP. Methods: One hundred consecutive subjects with high normal office BP (54±8 years, 42 males, baseline office BP: 132/82 mmHg, 24-hour BP: 122/76 mmHg) at baseline underwent a negative for ischemia treadmill exercise test. Arterial stiffness was evaluated on the basis of carotid to femoral pulse wave velocity (PWV) values and sympathetic drive was assessed by muscle sympathetic nerve activity (MSNA) based on established methodology. SBP/MET-slope defined as: peak systolic BP–resting SBP)/(peak MET-1) was assessed. Follow up was scheduled every 6 months for 3 consecutive years, where BP was measured both in the office and with ambulatory blood pressure monitoring. End point was the development of hypertension diagnosed from office blood pressure measurements and confirmed from ambulatory blood pressure monitoring. Results: Patients who developed hypertension (n=35) compared to those who remained normotensives (n=65) had at baseline higher prevalence of HRE (75% vs. 13%, p=0.026), higher levels of carotid to femoral PWV (8.35 vs. 7.5 m/sec, p=0.043) and MSNA (37 vs. 31 bursts per minute, p=0.04), while their metabolic profile did not differ at the follow up (p=NS for all). In those who developed hypertension, SBP/MET-slope was higher in all Bruce protocol stages till peak exercise (stage 1: 6.25 vs. 4.25, stage 2: 7.6 vs. 5.3, peak exercise: 7.22 vs. 5.1; p<0.05 for all). Additionally, those who remained normotensives compared to those who developed hypertension exhibited a higher exercise capacity (10 vs. 11.5 METs, p<0.05) and maximal heart rate at peak exercise (154 vs. 164, p=0.001). Conclusion: In subjects with high normal BP, those who develop hypertension during follow-up are characterized by more frequent HRE accompanied with lower exercise capacity, arterial stiffening and sympathetic overactivation. These results suggest that exercise BP response, along with PWV and MSNA estimation could contribute to identify high normal BP subjects who are more prone to become hypertensives. Funding Acknowledgement: Type of funding sources: None.

The pre-procedural presence of chronic total occlusions (CTO) in patients undergoing transcatheter aortic valve implantation (TAVI) could be a significant predictor of outcomes. This meta-analysis aims to investigate whether CTO presence significantly alters outcomes in TAVI patients. A systematic search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. After study selection, a random effect meta-analysis was performed. Seven studies with a total of 15,162 patients undergoing TAVI were included. There was no significant difference regarding in-hospital [Relative Risk (RR): 1.13; 95% Confidence Interval (95% CI): 0.82-1.55] and 1-year all-cause mortality (RR: 1.58; 95% CI: 0.71-3.50). Patients with CTO exhibited significantly increased rates of myocardial infarction (RR: 1.27, 95% CI: 1.07-1.51) and reduced rates of new pacemaker implantation (RR: 0.88, 95% CI: 0.79-0.98). No differences were found in cardiogenic shock (RR: 1.18, 95% CI: 0.97-1.44), acute kidney injury (RR: 1.06, 95% CI: 0.88-1.28), vascular complications (RR: 1.10, 95% CI: 0.91-1.33), or bleeding (RR: 1.01, 95% CI: 0.89-1.14). In TAVI patients, pre-procedural unrevascularized CTO presence is not related to short- or mid-term increased mortality. Further studies are needed to identify predictors of adverse events and phenotypes benefiting from revascularization.

Mitral transcatheter edge-to-edge repair (M-TEER) has emerged as a cornerstone in the management of severe mitral regurgitation, serving as a robust, low-risk alternative to conventional mitral valve surgery. Although thromboembolic risk remains a critical clinical challenge, that varies significantly across the clinical continuum, from pre-procedural substrates to post-procedural management. This review highlights the role of atrial cardiomyopathy in creating a prothrombotic milieu even prior to intervention, while during the procedure, device time emerges as a potentially dominant independent predictor of embolic burden, marking the periprocedural window as the period of peak hazard. Furthermore, this article addresses the notable disparity between the near-universal presence of subclinical ischemic lesions on magnetic resonance imaging and the infrequent incidence of overt neurological deficits. As the post-procedural phase is considered, we discuss the shift from standardized antithrombotic protocols to individualized strategies and the potential role of concomitant left atrial appendage occlusion. Ultimately, integrating these stage-specific clinical and procedural determinants with emerging technologies—like digital twins and artificial intelligence—represents a promising frontier for mitigating embolic risks, optimizing procedural planning and patient safety in the evolving landscape of mitral valve interventions.