• Subclinical leaflet thrombosis was recently linked to higher rates of stroke and transient ischemic attack after TAVR. EVs have emerged as a surrogate marker of endothelial dysfunction and cardiovascular risk. • This study demonstrates the role of EVs trapped within the native aortic valve in valvular dysfunction and thrombogenicity, and points at the contribution of the local angiotensin system/NADPH oxidases/SGLT2 pro-oxidant pathway. • Additional studies will be required to clarify the impact of SGLT2 in the limitation of EV-mediated injuries in patients with AS or following TAVR.

Transcatheter aortic valve replacement has emerged as a valuable alternative to surgical aortic valve replacement in patients with severe aortic stenosis. Given the expansion of transcatheter aortic valve replacement to lower‐risk and younger populations with longer life expectancy, the durability of transcatheter heart valves (THVs) has become an important issue that may impact cardiovascular outcomes. THVs share similarities with surgical valves but have unique features, including a trend to larger effective orifice area and less prosthesis–patient mismatch, interactions with the native valve, and crimping process, that may all potentially influence a THV's life span. Multiple mechanisms may lead to bioprosthetic valve dysfunction, including structural valve deterioration, thrombosis, endocarditis, and nonstructural valve deterioration. With an incidence of up to 12.3% 5 years after transcatheter aortic valve replacement, structural valve deterioration represents the ultimate consequence of fibrotic remodeling and calcification within the bioprosthesis, driven by thrombotic and inflammatory processes involving the native aortic valve and influenced by patient and procedural factors. Understanding these mechanisms is crucial for improving THV durability.

Background and Objective: Host defence mechanisms to counter virus infection include the activation of the broncho-alveolar haemostasis. Fibrin degradation products secondary to extravascular fibrin breakdown could contribute to the marked increase in D-Dimers during COVID-19. We sought to examine the prognostic value on lung injury of D-Dimers in non-critically ill COVID-19 patients without thrombotic events. Methods: This study retrospectively analysed hospitalized COVID-19 patients classified according to a D-Dimers threshold following the COVID-19 associated haemostatic abnormalities (CAHA) classification at baseline and at peak (Stage 1: D-Dimers less than three-fold above normal; Stage 2: D-Dimers three- to six-fold above normal; Stage 3: D-Dimers six-fold above normal). The primary endpoint was the occurrence of critical lung injuries on chest computed tomography. The secondary outcome was the composite of in-hospital death or transfer to the intensive care unit (ICU). Results: Among the 123 patients included, critical lung injuries were evidenced in 8 (11.9%) patients in Stage 1, 6 (20%) in Stage 2 and 15 (57.7%) in Stage 3 (p = 0.001). D-Dimers staging at peak was an independent predictor of critical lung injuries regardless of the inflammatory burden assessed by CRP levels (OR 2.70, 95% CI (1.50–4.86); p < 0.001) and was significantly associated with increased in-hospital death or ICU transfer (14.9 % in Stage 1, 50.0% in Stage 2 and 57.7% in Stage 3 (p < 0.001)). D-Dimers staging at peak was an independent predictor of in-hospital death or ICU transfer (OR 2.50, CI 95% (1.27–4.93); p = 0.008). Conclusions: In the absence of overt thrombotic events, D-Dimers quantification is a relevant marker of critical lung injuries and dismal patient outcome.

The impact of antithrombotic regimen and platelet inhibition extent on subclinical leaflet thrombosis (SLT) detected by cardiac multidetector computed tomography (MDCT) after transcatheter aortic valve replacement (TAVR) is not well established. Hypoattenuation affecting motion (HAM) has been proposed as a surrogate marker of SLT, and is characterized by hypoattenuated leaflet thickening (HALT) and concomitant reduction in leaflet motion (RELM). We sought to investigate (i) the prevalence of HAM and HALT after TAVR detected by MDCT, (ii) the predictors of SLT, (iii) the impact of oral anticoagulant (OAC) and platelet inhibition extent assessed by platelet reactivity index vasodilator stimulated phosphoprotein (PRI-VASP) and closure time adenosine diphosphate (CT-ADP) on SLT. Of 187 consecutive patients who underwent TAVR from 1 August 2017 to 31 March 2018, 90 of them had cardiac CT at relevant follow-up. Clinical, biological, echocardiographic, procedural characteristics and treatments were collected before, at discharge, and 1 year after TAVR. P2Y₁₂ platelet inhibition extent and primary haemostasis disorders were investigated using platelet PRI-VASP and CT-ADP point-of-care assays. Eighty-five post-TAVR CTs out of 90 were ranked for clarity and assessed with sufficient diagnostic quality. HAM was evidenced in 13 patients (15.3%) and HALT in 30 patients (35%). Procedural characteristics, including aortic valve calcium score, annulus size, or procedural heparin regimens, were equivalent between groups. Likewise, no impact of P2Y₁₂ inhibition (PRI-VASP) nor primary haemostasis disorders (CT-ADP) on SLT could be evidenced. No impact of SLT on valve deterioration evaluated by transthoracic echocardiography (TTE) and clinical events could be established at 12 months follow-up. By multivariate analysis, lack of oral anticoagulant therapy at discharge (HR 12.130 CI 95% (1.394–150.582); p = 0.028) and higher haemoglobin levels were evidenced as the sole independent predictors of SLT. In four patients with HAM, MDCT follow-up was obtained after initiation of OAC therapy and showed a complete regression of HAM. SLT was evidenced in a sizeable proportion of patients treated by TAVR and was mainly determined by the lack of oral anticoagulant therapy. Conversely, no impact of platelet inhibition extent on SLT could be evidenced.

While cardiovascular disease has been associated with an increased risk of coronavirus disease 2019 (COVID-19), no studies have described its clinical course in patients with aortic stenosis who had undergone transcatheter aortic valve replacement (TAVR). Numerous observational studies have reported an association between the A blood group and an increased susceptibility to SARS-CoV-2 infection. Our objective was to investigate the frequency and clinical course of COVID-19 in a large sample of patients who had undergone TAVR and to determine the associations of the ABO blood group with disease occurrence and outcomes. Patients who had undergone TAVR between 2010 and 2019 were included in this study and followed-up through the recent COVID-19 outbreak. The occurrence and severity (hospitalization and/or death) of COVID-19 and their associations with the ABO blood group served as the main outcome measures. Of the 1125 patients who had undergone TAVR, 403 (36%) died before 1 January 2020, and 20 (1.8%) were lost to follow-up. The study sample therefore consisted of 702 patients. Of them, we identified 22 cases (3.1%) with COVID-19. Fourteen patients (63.6%) were hospitalized or died of disease. Multivariable analysis identified the A blood group (vs. others) as the only independent predictor of COVID-19 in patients who had undergone TAVR (odds ratio (OR) = 6.32; 95% confidence interval (CI) = 2.11−18.92; p = 0.001). The A blood group (vs. others; OR = 8.27; 95% CI = 1.83−37.43, p = 0.006) and a history of cancer (OR = 4.99; 95% CI = 1.64−15.27, p = 0.005) were significantly and independently associated with disease severity (hospitalization and/or death). We conclude that patients who have undergone TAVR frequently have a number of cardiovascular comorbidities that may work to increase the risk of COVID-19. The subgroup with the A blood group was especially prone to developing the disease and showed unfavorable outcomes.

Subclinical leaflet thrombosis (SLT) following transcatheter aortic valve replacement occurs in 10% to 15% of patients at 1 month and up to 30% by 1 year, extending to perivalvular structures as subclinical aortic valve-complex thrombosis. We review contributing factors to SLT, including valve-specific parameters such as flow dynamics in the native sinus and neosinus, prosthesis sizing, deployment symmetry, implant depth, and commissural alignment; the persistent metabolic activity of retained calcified leaflets; and the impact of antithrombotic therapy on SLT incidence. Although oral anticoagulation reduces imaging-detected SLT, it increases bleeding and mortality. This review offers a comprehensive analysis integrating device geometry, sinus flow dynamics, and native tissue activity to inform personalized, time-limited anticoagulation strategies in high-risk patients, thereby optimizing the thrombosis-bleeding balance and enhancing transcatheter aortic valve replacement outcomes.