Background: IHD is determined by an inadequate coronary blood supply to the myocardium, and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Validation of results in larger cohorts and new populations is needed. The aim of this study is to evaluate the associations between the allelic variants of the eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility and its clinical presentation. Methods: A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD); G2, coronary microvascular dysfunction (CMD); and G3, a control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG and TT, of rs1799983 for the NOS3 gene, encoding for eNOS, was performed. Results: rs1799983_GT was significantly more expressed by the ischemic groups (G1 and G2) compared to G3. The TT variant was significantly more expressed by the G1 group, compared to the G2 group. Among ischemic patients, GT was significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentations. In the multivariate analysis, the allelic variant GT was found to potentially represent an independent predictor of IHD and ACS presentation. Conclusion: The presence of the SNP rs1799983_GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently of cardiovascular risk factors. These results may be useful for the prediction of IHD development, particularly with an acute clinical manifestation. They may allow the early identification of patients at high risk of developing IHD with an ACS, promoting a genetic-based prevention strategy against IHD.

Chronic kidney disease (CKD) and valvular heart disease (VHD) frequently coexist and are associated with a significant increase in morbidity and mortality. Their interplay is complex and multifactorial, involving shared pathophysiological mechanisms such as chronic inflammation, mineral and bone disorder, vascular and valvular calcification, and neurohormonal activation. These factors contribute to a bidirectional relationship in which each condition can exacerbate the progression and clinical consequences of the other. This review provides a comprehensive synthesis of the current evidence on the epidemiology, pathogenesis, and clinical impact of the CKD–VHD association. Special attention is given to the mechanisms underlying valvular calcification in the uremic milieu, the diagnostic challenges posed by overlapping symptoms, and the prognostic implications of valvular disease in patients with impaired renal function. Furthermore, this paper critically examines the available therapeutic options, including medical management, surgical and transcatheter interventions, and their outcomes in CKD patients. Given the limited evidence from randomized controlled trials in this population, our work also identifies key knowledge gaps and highlights future research directions, advocating for multidisciplinary approaches and tailored strategies. A better understanding of this cardio‐renal interaction is crucial to optimize clinical decision‐making and improve patient outcomes.

Background and objectives: Valve-in-valve transcatheter aortic valve replacement (ViV TAVR) has become an established treatment for failed surgical bioprostheses in patients at high surgical risk. However, procedures performed in degenerated stentless aortic valves remain particularly challenging because of the absence of a radiopaque frame, variable surgical implantation techniques, and a potentially increased risk of coronary obstruction. Evidence in this specific setting is limited. We conducted a systematic review of the literature to identify studies reporting ViV TAVI in degenerated stentless surgical bioprostheses. Materials and methods: Case reports and case series were included when patient-level or clearly identifiable data were available. Baseline characteristics, anatomical features, procedural strategies, and clinical outcomes were extracted and analyzed using a descriptive approach. A total of 54 studies were included, encompassing 294 ViV TAVI procedures performed in failed stentless aortic valves. Results: The mean patient age was 73.9 years, and the average STS-PROM score was 13.45%, reflecting a high-risk population. The most frequently treated prosthesis was the Medtronic Freestyle valve, and the predominant mechanism of failure was regurgitation. Transfemoral access represented the most common approach, while balloon-expandable and self-expanding transcatheter valves were used with similar frequency. Coronary protection strategies were adopted in a minority of procedures, whereas adjunctive procedural techniques such as pre- or post-dilation were relatively common. Device-related complications were mainly driven by coronary obstruction, while cardiac complications included myocardial infarction and unplanned coronary intervention. Overall, VARC-3 device success was achieved in the majority of procedures, with acceptable short-term mortality despite the complexity of the treated population. Conclusions: ViV TAVR in degenerated stentless bioprostheses appears feasible and generally effective but remains associated with specific procedural challenges, particularly related to coronary obstruction risk. Careful anatomical assessment and tailored procedural planning are essential, and larger contemporary studies are needed to better define optimal management strategies in this complex setting.

Aortic aneurysms are associated with substantial morbidity and mortalitbecause of the risk of progressive dilation, rupture, and related acute aortic complications. Although diabetes mellitus (DM) is a major cardiovascular risk factor, epidemiological studies have consistently reported an inverse association between DM and the prevalence and progression of abdominal aortic aneurysm (AAA). More limited evidence suggests an inverse association between diabetes and thoracic aortic aneurysm. Accordingly, this review focuses primarily on AAA; where available, evidence concerning TAA and aortic dissection is discussed separately. This review examines the pathophysiological mechanisms underlying the inverse association between DM and aortic aneurysm development. Key mechanisms include the effects of hyperglycemia on extracellular matrix remodeling, particularly through modulation of matrix metalloproteinase (MMP-2 and MMP-9) activity, increased formation of advanced glycation end products (AGEs), and enhanced collagen cross-linking. Experimental and translational evidence suggests that diabetes may influence inflammatory cell states and mural neoangiogenesis, although these effects appear to be context- and model-dependent. Antidiabetic therapies, including metformin, DPP-4 inhibitors, GLP-1 receptor agonists, thiazolidinediones, sulfonylureas, and SGLT2 inhibitors, may also contribute to the observed association through glucose-lowering and/or pleiotropic vascular effects. Furthermore, diabetes-related changes in aortic wall biomechanics, including increased wall thickness and potentially altered wall stress, may contribute to aneurysm stabilization. Overall, DM is associated with a lower prevalence and slower progression of AAA, potentially through a combination of metabolic, inflammatory, structural, and treatment-related mechanisms. These observations should not be interpreted as evidence that diabetes or chronic hyperglycemia is clinically beneficial; rather, they may help identify biological pathways relevant to aneurysm development and progression.