Background: Myocardial bridge (MB) is a frequent coronary artery anomaly. The aims of this study are to describe the use of antiplatelet therapy (APT) in a cohort of patients with MB and assess its impact on ischemic and bleeding events. Methods: The RIALTO (Myocardial Bridge Evaluation Towards Personalized Medicine) registry (ID: NCT05111418) is an ambispective multicenter observational registry, enrolling patients with a clinical indication to coronary angiography and evidence of MB. The present analysis included patients with MB without any preexisting indication for APT/anticoagulant therapy according to guidelines. Patients were categorized into 2 groups: single APT or no APT based on discharge prescriptions. The primary end point was the time to first occurrence of net adverse clinical events, defined as a composite of cardiovascular death, nonfatal myocardial infarction, unplanned or elective coronary angiography, ischemic cerebrovascular events, and any bleeding. Results: Out of 486 enrolled patients with MB, 221 (mean age: 60 years, 66% male) were included in this analysis. One hundred and forty‐one patients (64%) received single APT. At a median follow‐up of 1661 days, patients with MB receiving single APT had a higher rate of net adverse clinical events (adjusted hazard ratio [aHR], 6.2; P =0.03), mainly driven by a higher rate of minor bleeding events (aHR, 10.58; P =0.02), with no difference regarding ischemic events. Results were consistent after 1:1 propensity‐score matching sensitivity analyses. Conclusions: The prescription of single APT is common in patients with MB, and it seems to be associated with an increased risk of bleeding, in the absence of a beneficial effect on ischemic events.

Atherosclerosis is a complex, multifactorial disease that progresses through distinct stages: initiation, progression, and complication, ultimately leading to acute coronary syndromes (ACS). Endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and macrophages are central players in this process, influencing plaque stability and vulnerability. Insulin-Like Growth Factor 1 (IGF-1), soluble-Klotho (S-Klotho), and the Growth Hormone Receptor exon 3 deletion polymorphism (GHRd3) have emerged as key modulators of vascular health, impacting these cellular components through various mechanisms. IGF-1 supports endothelial function, enhances VSMC survival and migration, and mitigates inflammation by inhibiting macrophage recruitment and activation, ultimately reducing the risk of plaque destabilization. S-Klotho, an anti-aging protein with potent anti-inflammatory and antioxidant properties, has been linked to vascular protection, with its deficiency associated with endothelial dysfunction, vascular calcification, and impaired VSMC survival. Evidence suggests that IGF-1 may enhance Klotho shedding, indicating a potential synergistic role in maintaining vascular integrity. This narrative review aims to outline the fundamental stages of atherosclerosis progression, consolidate current evidence on the roles of IGF-1 and S-Klotho in modulating key cellular components of atherosclerosis, and shed light on their potential involvement in plaque healing—an area that remains largely unexplored. By integrating established molecular mechanisms, we explore how these factors may contribute to endothelial integrity, VSMC survival, and macrophage activation and polarization, potentially shaping a more stable plaque phenotype and influencing future therapeutic strategies in cardiovascular disease.

Background. Before transcatheter aortic valve implantation (TAVI), predicted prosthesis–patient mismatch (PPM) is graded from a reference effective orifice area (EOA) taken from interchangeably-used sources that were never compared.Methods. In 1,419 consecutive transfemoral native-valve TAVI patients, predicted EOA was derived four ways: Transcatheter Valve Therapy (TVT) registry values; manufacturer/bench values (IFU/Bench); a CT-derived EOA from the CT-indicated size; and the CT annular area directly (PPMp2), graded by VARC-3. With no method as reference, the four were compared against each other, the residual gradient and mortality.Results. No patient had severe PPM; moderate PPM ranged 0.6–11.7%. The methods were not equivalent (Cochran Q = 78.9, p < 0.001), five of six pairs differing. For a gradient ≥20 mmHg, TVT registry and CT-derived-EOA were indistinguishable (ΔAUC 0.019, p = 0.103), whereas TVT registry outperformed IFU/Bench (0.057, p = 0.010) and PPMp2 (0.106, p = 0.005). Over a median 36.7 months, 363/1,177 died; no method predicted mortality (hazard ratios 0.99–1.13, all p > 0.45; C-indices 0.51–0.53).Conclusions. The sources differ and rank against the residual gradient, yet none is prognostic. Predicted PPM is a measurement problem, not a risk marker: the EOA source and VARC-3 threshold should always be stated.