Search Results (323)

Background/Objectives: Elevated lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor associated with atherosclerotic cardiovascular disease and calcific aortic valve disease. Historically, therapeutic options for reducing Lp(a) have been limited. This study aimed to characterize the clinical development landscape of emerging Lp(a)-targeted therapies, evaluate endpoint assessment strategies, and summarize available efficacy evidence from investigational agents. Methods: A qualitative clinical trial landscape review was conducted using ClinicalTrials.gov. Interventional Phase I–III studies evaluating therapies specifically targeting Lp(a) were identified through a structured registry search performed on 5 November 2025. Eligible studies were screened according to predefined inclusion and exclusion criteria. Extracted data included trial characteristics, therapeutic class, endpoint methodologies, and published efficacy outcomes. Data were synthesized narratively. Results: Twenty clinical trials met the eligibility criteria. Three therapeutic classes were identified: antisense oligonucleotides (ASOs), small interfering RNA (siRNA)-based therapies, and small-molecule inhibitors. Pelacarsen represented the sole ASO program, whereas siRNA-based therapies constituted the largest therapeutic category. Five studies were designed as cardiovascular outcomes trials. Percent change from baseline in circulating Lp(a) concentration was the most frequently used efficacy endpoint. Published data demonstrated substantial reductions in Lp(a) concentrations across all major therapeutic platforms. Available non-head-to-head published evidence showed substantial Lp(a) reductions across several investigational agents, including siRNA-based therapies, pelacarsen, and muvalaplin, although differences between studies preclude direct comparison between therapeutic platforms. Conclusions: The Lp(a) therapeutic landscape has rapidly evolved, with RNA-based therapies demonstrating unprecedented reductions in circulating Lp(a) concentrations. Ongoing cardiovascular outcomes trials will determine whether these reductions translate into meaningful cardiovascular benefits, establish Lp(a) as a therapeutic target in cardiovascular prevention and clarify the long-term safety and risk–benefit profile of Lp(a)-targeted therapies. Full article

Background: Low-flow, low-gradient aortic stenosis with reduced left ventricular ejection fraction is a heterogeneous condition with challenging severity assessment. Aortic valve calcification reflects fibro-calcific remodeling, while oxidative stress plays a key role in its pathogenesis. Serum uric acid, a marker of oxidative stress, may be associated with valvular calcification. This study investigated the relationship between serum uric acid levels and aortic valve calcification in this population. Methods: This retrospective study included 85 patients. Aortic valve calcification was quantified using computed tomography with the Agatston method, and patients were categorized as true severe or pseudo-severe according to sex-specific calcium thresholds. Of the patients, 57 were classified as true severe and 28 as pseudo-severe aortic stenosis. Results: Patients with higher calcification burden had significantly elevated serum uric acid levels (6.77 ± 1.57 vs. 5.08 ± 1.10 mg/dL, p < 0.001). Serum uric acid showed a modest correlation with aortic valve calcium score (ρ = 0.339, p = 0.002) and remained independently associated with CT-defined true severe low-flow, low-gradient aortic stenosis in multivariable analysis. ROC analysis yielded an area under the curve of 0.823 and identified a serum uric acid threshold of 5.45 mg/dL associated with a greater likelihood of CT-defined true severe low-flow, low-gradient aortic stenosis. Conclusions: Serum uric acid is associated with CT-derived aortic valve calcification and may provide insight into underlying fibro-calcific remodeling in this population. Full article

Background and Objectives: Transcatheter aortic valve implantation (TAVI) is the standard therapy for patients with severe aortic stenosis at intermediate or high surgical risk. Mitral annular calcification (MAC) is frequently observed in this population and has been linked to adverse cardiovascular outcomes. This study evaluated the association between MAC and TAVI-related complications and mortality, and identified predictors of all-cause mortality and permanent pacemaker implantation (PPI) following TAVI. Materials and Methods: Patients undergoing self-expanding TAVI between January 2010 and June 2020 were retrospectively analyzed. Outcomes included TAVI-related complications, in-hospital and long-term mortality, and predictors of all-cause mortality and PPI. Results: A total of 245 patients (98 men [40%], mean age 76.3 ± 8.3 years) were included. Mean left ventricular ejection fraction was 54.8 ± 11.4%, and aortic valve area was 0.74 ± 0.14 cm². MAC was present in 148 patients (60.4%). Pericardial effusion (26.4% vs. 12.4%, p = 0.013) and acute kidney injury (21.6% vs. 7.2%, p = 0.005) were significantly more frequent in patients with MAC. PPI was required in 42 patients (17.8%). In-hospital mortality occurred in 14 patients (5.7%), and all-cause mortality was observed in 89 patients (36.3%) during a median follow-up of 23.1 months (IQR, 11.6–44.3). MAC extension into the left ventricular outflow tract was the only independent predictor of PPI (OR: 3.32, p = 0.002). Independent predictors of all-cause mortality included use of renin–angiotensin–aldosterone system blockers (HR: 0.54, p = 0.012), hemoglobin level (HR: 0.79, p = 0.006), severe MAC (HR: 1.94, p = 0.024), and post-TAVI atrial fibrillation (HR: 2.39, p = 0.002). Conclusions: MAC is common in TAVI patients and is associated with increased procedural complications, including higher rates of pericardial effusion and acute kidney injury. Greater MAC severity independently predicts higher all-cause mortality. In addition, MAC extension into the left ventricular outflow tract is an independent predictor of PPI following self-expanding TAVI, emphasizing the importance of comprehensive pre-procedural imaging. Full article

Background: The extent and distribution of valvular calcification may differ across hemodynamic subtypes of severe aortic stenosis (AS), but their clinical relevance in patients undergoing transcatheter aortic valve implantation (TAVI) remains incompletely understood. Methods: We retrospectively analyzed 315 consecutive patients undergoing transfemoral TAVI for symptomatic severe AS at a single center between January 2020 and December 2022. Aortic valve calcification was assessed by aortic valve calcium score (AVCS) on non-contrast CT and by calcification volume (CV) on contrast-enhanced CT. Patients were classified as high-gradient aortic stenosis (HGAS), classical low-flow low-gradient aortic stenosis (cLFLGAS), paradoxical low-flow low-gradient aortic stenosis (pLFLGAS), or normal-flow low-gradient aortic stenosis (NFLGAS). Results: HGAS represented 70.8% of the cohort, whereas low-gradient AS subtypes accounted for the remaining cases. Valvular calcification burden was highest in HGAS and consistently lower in all low-gradient phenotypes, particularly in pLFLGAS. The non-coronary cusp was the most heavily calcified cusp across all groups. Neither AVCS nor CV was associated with all-cause mortality up to 2 years after TAVI. Conclusions: Low-gradient AS subtypes exhibit a lower valvular calcification burden than HGAS, but these differences did not translate into differences in 2-year mortality after transfemoral TAVI in this particular cohort. Full article

Background: An aorto-right ventricular fistula (ARVF) secondary to membranous septum rupture is an exceptionally rare complication after surgical aortic valve replacement (SAVR). While sutureless prostheses such as the Perceval valve have gained wide acceptance due to reduced cross-clamp times and procedural simplification, the reported adverse events predominantly include conduction disturbances and paravalvular leaks. Structural septal disruption remains sparsely described. We report a case of an early ARVF after Perceval implantation and review the pathophysiological and procedural mechanisms implicated in septal injury following sutureless and transcatheter aortic valve interventions. Case Description: A 66-year-old woman with severe bicuspid aortic valve stenosis underwent SAVR via a median sternotomy using a Perceval XL prosthesis after meticulous annular decalcification and sizing. Immediate intraoperative transesophageal echocardiography (TEE) confirmed optimal seating without any paravalvular regurgitation. Within 24 h, the patient developed a complete atrioventricular block followed by cardiogenic shock. A repeat TEE revealed a large ARVF with significant left-to-right shunt. Emergent re-exploration identified a membranous septum tear. The Perceval prosthesis was explanted, the defect was closed with a reinforced patch repair, and a 27 mm Inspiris Resilia bioprosthesis was implanted. Peripheral veno-arterial ECMO support was required temporarily. The patient recovered and remained free of prosthetic dysfunction at the two-year follow-up. Discussion: Membranous septum rupture after AVR has an estimated incidence of 0.4–1.5% in TAVR cohorts but is virtually unreported with Perceval valves. The mechanisms are thought to be chronic radial stress from oversized or malpositioned prostheses. Case reports with TAVR devices emphasize oversizing as a risk factor. Predictive factors for septal injury in sutureless AVR mirror those for conduction disturbances: valve oversizing, shallow infra-annular septal length, heavy calcification, and prior valve surgery. Preventive measures, such as strict sizing protocols, the avoidance of balloon dilation, and optimized implantation depth, have reduced conduction complications and may mitigate septal trauma. The treatment choice, whether percutaneous or surgical closure, depends on hemodynamic stability, defect size and anatomy, and operative risk. Conclusions: Early ARVF after Perceval implantation is exceedingly rare but potentially catastrophic. Strict adherence to sizing principles, awareness of septal anatomy, and prompt management, percutaneous in selected stable cases or surgical in acute large defects, are essential to optimize outcomes in sutureless AVR. Full article

Background: Transcatheter mitral valve implantation (TMVI) represents an evolving therapeutic strategy for patients with severe mitral valve disease who are at high or prohibitive risk for conventional surgery. Since the first human implantation in 2012, multiple dedicated and adapted devices have entered clinical investigation, yet only one dedicated system—the Tendyne prosthesis (Abbott Structural)—holds regulatory approval. This systematic review evaluates the current landscape of available and emerging TMVI devices, examines the clinical outcome data, discusses key indications and limitations, analyses the role of computed tomography (CT) in predicting left ventricular outflow tract (LVOT) obstruction caused by the unopposed anterior mitral leaflet, and compares TMVI outcomes with conventional surgical mitral valve replacement (SMVR) in the specific context of severe mitral annular calcification (MAC). Methods: A systematic search of PubMed, EMBASE, Cochrane Central, and Web of Science was performed for studies published from January 2010 to March 2025 reporting outcomes of TMVI in native valve disease, valve-in-valve (ViV), valve-in-ring (ViR), or valve-in-MAC (ViMAC) procedures. Studies reporting CT-based LVOT planning, neo-LVOT quantification, and LVOT obstruction outcomes were specifically sought. Meta-analyses comparing TMVI with redo surgical mitral valve replacement were included. A total of 63 studies (n > 12,000 patients across all subgroups) were included in the qualitative synthesis; 28 studies were included in the quantitative synthesis. Results: Nine dedicated TMVI devices are currently under clinical investigation, with only Tendyne holding CE Mark and FDA approval. In ViV/ViR cohorts, TMVI was associated with significantly lower in-hospital mortality (OR 0.72, 95% CI 0.57–0.92; p = 0.008) and 30-day mortality (OR 0.49; p = 0.04) compared with redo SMVR, with no significant difference at one year (OR 1.03; p = 0.91). In ViMAC cohorts, 30-day mortality ranged from 14 to 24%, which was substantially higher than in the ViV outcomes. CT-based virtual simulation of the neo-LVOT area—the residual outflow tract created by anterior mitral leaflet displacement—is the most validated predictor of LVOT obstruction, with a threshold of ≤1.7 cm² yielding 96% sensitivity and 92% specificity. The LAMPOON technique (laceration of the anterior mitral leaflet to prevent outflow obstruction) has expanded the eligibility for patients who were previously excluded due to LVOT risk. Surgical MVR in severe MAC carries a median 30-day mortality of 6.3% (range 0–27.3%), while ViMAC TMVI with dedicated devices yields 6.8% 30-day mortality, without a definitive randomised comparison. Conclusions: TMVI offers a viable alternative to redo surgery in high-risk patients with failed bioprostheses or rings. In severe MAC, both surgical and transcatheter approaches carry significant risk; patient selection, CT-guided LVOT planning, and use of dedicated devices are critical to optimising outcomes. The ongoing SUMMIT randomised controlled trial will provide the first high-quality comparative data. Future developments in transseptal delivery and LVOT-safe device architectures are expected to broaden the eligible population. Full article

Background: Cognitive impairment is a common and clinically significant complication in patients undergoing peritoneal dialysis, a vulnerable population with multiple comorbidities. However, its underlying determinants remain incompletely understood. Vascular calcification, as a marker of systemic vascular pathology, has been suggested to be associated with cognitive dysfunction. This study aimed to evaluate the relationship between intracranial and valvular calcification and cognitive dysfunction in peritoneal dialysis patients. Methods: This single-center cross-sectional study included patients receiving peritoneal dialysis. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Intracranial and valvular calcifications were determined based on imaging findings. Clinical, demographic, and laboratory parameters were analyzed. Logistic regression analysis was used to identify factors associated with cognitive dysfunction, and receiver operating characteristic (ROC) analysis was performed to assess discriminative performance. Results: A total of 95 patients were included. Patients with cognitive dysfunction were older and more frequently female. In univariate analysis, age, female sex, and mitral valve calcification were significantly associated with cognitive dysfunction. After multivariable adjustment, only age (OR: 1.06, p = 0.02) and female sex (OR: 3.4, p = 0.03) remained independently associated. ROC analysis showed limited discriminative performance (AUC: 0.63). Conclusions: Calcification parameters were associated with cognitive dysfunction in unadjusted analyses but did not remain independent predictors after adjustment. Age was the strongest factor associated with cognitive dysfunction, while female sex was also independently associated with increased risk. These findings suggest that calcification burden may reflect cumulative vascular aging and comorbidity rather than serving as a standalone predictor of cognitive impairment. Full article

The dynamics of calcium carbonate structures in marine organisms (skeletons and shells) has become increasingly important due to heightened interest in marine environmental acidification. Research into molluscan shell corrosion and calcification in response to acidification is typically carried out in laboratory-controlled settings, which often overlooks the intricate interactions found in natural environments. Mollusks inhabiting intertidal zones are especially susceptible to intense shell weathering caused by tidal cycles of heating, cooling, wetting, and drying, exacerbated by solar radiation during periods of air exposure. We investigated the effect of sun exposure (solar radiative heating) on both outer shell corrosion and inner shell compensatory calcification in the tropical oyster, Saccostrea scyphophilla. Shell properties were compared between oysters from neighboring populations in sun-exposed and shaded habitats. Habitat temperatures were measured using iButtons, and right shell valve corrosion was quantified. Compensatory calcification was assessed through measurements of shell thickness, shell density, shell compression strength, and mineralogical properties. Our results revealed that oysters in the sun that experience global irradiance, higher temperature peaks and broader daily temperature ranges (averaging an increase of 10 °C) show considerably greater outer shell surface corrosion (87%) compared to shaded oysters (31%) that experience only diffuse irradiance. Sun-exposed shells also become thickened in the midsection and around the adductor muscle, and they are slightly stronger, indicating compensation for the outer shell loss. These findings highlight the need for caution when interpreting molluscan shell dynamics based on laboratory marine acidification protocols that fail to account for the many natural environmental factors influencing shell formation and dissolution. Full article

Gla-rich protein (GRP), also known as UCMA, is a vitamin K-dependent protein that has emerged as an important regulator of pathological calcification and inflammation. Vascular calcification is a major complication of chronic kidney disease and cardiovascular disorders and is now recognized as an active and tightly regulated process rather than a passive accumulation of minerals. Increasing evidence indicates that GRP plays a protective role in mineral homeostasis through its strong calcium-binding capacity and its dependence on vitamin K-mediated gamma carboxylation. This work represents a comprehensive narrative review aimed at summarizing and critically discussing the current scientific knowledge on GRP. Available experimental and clinical data are analyzed with respect to gene expression, molecular regulation, vitamin K dependency, and underlying mechanisms of action. Particular emphasis is placed on the dual function of GRP in inhibiting ectopic calcification and modulating inflammatory responses. The evidence linking altered GRP levels or changes in its carboxylation status with chronic kidney disease, vascular calcification, calcific aortic valve disease, osteoarthritis, and tumor-associated microcalcifications is systematically examined. Current findings collectively support the concept that GRP is a multifunctional protein operating at the interface of mineral metabolism, inflammation, and tissue remodeling. Despite promising experimental data, important knowledge gaps remain, including the absence of standardized assays capable of distinguishing different GRP forms and the lack of longitudinal clinical studies evaluating its predictive value. This manuscript highlights the potential of GRP as a biomarker of disturbed mineral homeostasis and cardiovascular risk, while emphasizing the need for further research to clarify its precise biological functions and clinical relevance. Full article

Background: Lipoprotein(a) [Lp(a)] is an inherited cardiovascular risk factor, but its relationship with coronary anatomical complexity, plaque phenotype, and outcomes after percutaneous coronary intervention (PCI) remains incompletely defined. Methods: We conducted a systematic review and meta-analysis of studies evaluating the association between circulating Lp(a) levels and coronary disease characteristics, post-PCI clinical outcomes, stent-related adverse outcomes, and aortic valve disease. Results: Twenty-six studies were included. Elevated Lp(a) levels were associated with greater coronary anatomical complexity and a higher risk of major adverse cardiovascular events after PCI (HR 1.4, 95% CI 1.2–1.7). The strongest associations were observed for stent-related adverse outcomes, including restenosis (OR 3.23, 95% CI 2.2–4.8) and target vessel revascularization (OR 2.6, 95% CI 1.6–4.4). Higher Lp(a) levels were also associated with vulnerable plaque features and aortic valve calcification. Conclusions: Elevated Lp(a) is associated with greater coronary disease complexity and adverse outcomes after PCI. Elevated Lp(a) may represent a biological marker identifying high-risk patients and providing additional insight for personalized risk stratification and procedural decision-making in patients undergoing PCI. Full article

Transcatheter aortic valve implantation (TAVI) has transformed the management of severe aortic stenosis (AS), evolving from a therapy reserved for inoperable patients to a viable treatment across the spectrum of surgical risk. This success has stimulated innovation in transcatheter therapies for other valvular heart diseases, including aortic regurgitation (AR). In contrast to AS, AR is characterised by heterogeneous aetiologies, absence of annular calcification, larger and more elliptical annular dimensions, and concomitant aortopathy. These challenges have limited the efficacy and safety of conventional transcatheter aortic valves (TAVs), use of which in pure native AR is associated with high rates of valve embolisation, significant residual regurgitation, permanent pacemaker implantation, and mortality. The development of dedicated TAVs designed specifically for the treatment of AR has addressed many of these anatomical challenges. The JenaValve Trilogy and J-Valve systems incorporate leaflet-grasping mechanisms that enable secure anchoring independent of calcification, resulting in transformation of procedural and clinical outcomes. Recent prospective registry data, including the landmark ALIGN-AR trial, demonstrate high technical and procedural success rates, low residual regurgitation, acceptable safety profiles, and meaningful improvements in functional status and ventricular remodelling. These data have informed contemporary guideline updates, with the 2025 European Society of Cardiology (ESC)/European Association of Cardiothoracic Surgery (EACTS) Guidelines for the management of valvular heart disease issuing the first conditional recommendation for TAVI in selected patients with severe AR and the National Institute for Health and Care Excellence (NICE) recommending TAVI for native AR in patients for whom surgical AVR is not available or is high risk. This review summarises the clinical implications of AR, examines current guideline recommendations for management, and critically appraises the evidence supporting transcatheter treatment strategies. Full article

Background/Objectives: Transcatheter aortic valve implantation (TAVI) in patients with bicuspid aortic valve (BAV) remains associated with higher rates of residual paravalvular leak (PVL), which confers a two-fold increase in mortality. Despite procedural optimization including balloon post-dilatation, a subset of patients exhibit residual ≥moderate PVL. Pre-procedural identification of these patients could guide procedural planning. Methods: We retrospectively analyzed 402 BAV patients who underwent TAVI with self-expanding valves and balloon post-dilatation between January 2016 and June 2024. A multi-modal deep learning model (Model B) was developed, integrating a 3D ResNet encoder for computed tomography (CT) imaging features with a multilayer perceptron (MLP) for clinical variables, fused via a cross-attention mechanism. Its performance was compared against a conventional model (Model A) combining clinical variables with manually derived CT measurements. Both models were evaluated on identical test folds using 5-fold stratified cross-validation. Results: Of 402 patients, 36 (9.0%) had residual ≥moderate PVL, associated with significantly larger aortic root dimensions at all anatomical levels and greater aortic valve calcification volume (median 887.6 vs. 559.2 mm³; p = 0.004). Model A achieved a mean AUC of 0.694 (95% CI: 0.596–0.792). Model B achieved a mean AUC of 0.822 (95% CI: 0.680–0.964), with a specificity of 0.971, accuracy of 0.881, and PPV of 0.860, while sensitivity was 0.429, reflecting the limited number of outcome events in this cohort. Conclusions: A multi-modal deep learning model integrating expert-segmented CT imaging with clinical variables demonstrated significantly improved discrimination over the conventional approach in this internal cohort for predicting residual PVL in BAV-TAVI, supporting the integration of segmentation-guided deep learning into pre-procedural TAVI planning. However, given the modest number of outcome events, external validation is required to confirm the generalizability of these findings. Full article

Background: Infective endocarditis (IE) affects both native and prosthetic heart valves, the endocardial surface, as well as cardiac implantable electronic devices. Identifying specific IE biomarkers for its early risk stratification remains crucial, particularly in cases with blood culture-negative endocarditis. Methods: Eleven native heart valves obtained from IE and calcific aortic valve disease (CAVD) patients were analyzed. Immunohistochemical analysis of a pan-leukocyte marker (CD45), macrophage marker (CD68), T-lymphocyte marker (CD3), B-lymphocyte marker (CD19), neutrophil myeloperoxidase (MPO), and marker of vascular endothelial cells (CD31) was performed. Differentially expressed genes (DEGs) were identified by whole-transcriptome sequencing; proteomic profiling was performed by dot-blotting. Results: The immunophenotyping demonstrates the infiltration of macrophages and neutrophils, as well as occasional T-lymphocytes in the IE-affected aortic valves, and the CAVD-affected heart valves were characterized by the absence of neutrophils. For the whole-transcriptome sequencing, 157 DEGs were identified: 124 DEGs were upregulated, and 33 genes were downregulated in the IE-affected heart valves compared to the CAVD-affected ones. According to the dot-blotting, 35 cytokines were identified in the studied heart valves, but only 21 molecules were expressed in both IE and CAVD-affected heart valves. Analysis of proteases and their inhibitors allowed the identification of 13 protease molecules and 18 enzyme inhibitor molecules in all examined heart valves. Conclusions: The results of the present study can help to improve our understanding of the IE pathogenesis. In addition, we identified the candidate cellular and molecular-genetic features of IE-affected native heart valves. Full article

Large animal models are a critical component of the preclinical evaluation of mechanical cardiac implants, enabling assessment of safety and performance under physiological conditions that cannot be adequately reproduced in vitro. Choosing a suitable animal model is important for both scientifically valid and ethically responsible preclinical evaluation. However, interspecies differences between animal models and humans pose significant challenges for relevant translation of preclinical findings to clinical outcomes. This narrative review provides a comprehensive overview of commonly used large animal models (sheep, goats, pigs, and calves) for the preclinical assessment of mechanical cardiac implants, including prosthetic heart valves, ventricular assist devices, and total artificial hearts. We summarize key anatomical and physiological characteristics that influence device implantation, chronic follow-up, and translational value. Emphasis is placed on three critical outcome domains for preclinical evaluation of mechanical cardiac implants: calcification, thrombogenicity, and hemodynamic performance. Species- and age-dependent differences in calcification are reviewed, identifying juvenile sheep as a worst-case model for early manifestation and detection of graft mineralization. Interspecies differences in coagulation biology are examined, showing attenuated platelet responses in sheep and closer similarity between porcine and human platelet behavior, supporting pigs as the preferred thrombogenicity model. Hemodynamic evaluation strategies in acute and chronic large-animal studies are discussed, with particular emphasis on circulatory demands influenced by somatic growth and on device adaptability under varying loading conditions. Overall, this review provides practical, outcome-driven guidance for large animal model selection and experimental design in mechanical cardiac implant research, while identifying key limitations, knowledge gaps, and the need for standardized reporting to improve the translational reliability of preclinical studies. Based on the findings presented in this review, we conclude that there is no single animal model capable of evaluating all relevant aspects of a device. Instead, different animal models provide distinct advantages depending on the outcomes of interest. Full article

Background: The prevalence of severe aortic stenosis (AS) is increasing, in accordance with a longer life expectancy. Aortic valve calcification is a multifactorial pathological process involving a complex interplay between different types of regenerative cellular and genetic factors. Among these cells, endothelial progenitor cells (EPCs) and their osteoblastic phenotype subpopulation (EPC-OCNs) have been implicated in vascular remodeling and disease progression. Objectives: To assess longitudinal changes in EPC and EPC-OCN levels in patients with severe symptomatic AS undergoing transcatheter aortic valve implantation (TAVI). Methods: In this prospective observational study, 65 patients with severe AS undergoing TAVI were enrolled. Circulating EPC and EPC-OCN levels were quantified by flow cytometry before the procedure, at 4 ± 1 days, and at 90 ± 29 days after TAVI. EPCs were defined by expression of CD133, CD34, and VEGFR-2. Results: Circulating EPC levels remained unchanged throughout the follow-up. In contrast, circulating EPC-OCNs increased significantly over time. Specifically, CD133+/VEGFR-2+/OCN+ cells rose from 2.50% to 6.25%, CD34+/VEGFR-2+/OCN+ from 2.04% to 4.05%, and VEGFR-2+/OCN+ from 1.46% to 3.01% (all p < 0.01). This suggests an osteogenic response to TAVI, while classical endothelial repair mechanisms were not systemically activated. Conclusions: EPC-OCNs increased significantly following TAVI, possibly reflecting ongoing tissue remodeling or calcification processes. In contrast, the stability of classical EPCs levels suggests limited systemic endothelial regeneration. These observations underscore the potential role of EPC-OCNs as markers or modulators of pre- and post-TAVI vascular remodeling. Full article