Impact of pulmonary hypertension on outcomes after TEER in patients suffering from mitral regurgitation.

AIM: Data on associations of invasively determined hemodynamic parameters with procedural success and outcomes in patients suffering from mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair of the mitral valve (M-TEER) is limited. METHODS AND RESULTS: We enrolled 239 patients with symptomatic MR of grade 2 + , who received M-TEER. All patients underwent extensive pre-interventional invasive hemodynamic measurements via right heart catheterization (mean pulmonary arterial pressure (mPAP), systolic- (PAPsys) and diastolic pulmonary arterial pressure (PAPdia), pulmonary arterial wedge pressure (PAWP), a-wave, v-wave, pulmonary vascular resistance (PVR), transpulmonary pressure gradient (TPG), cardiac index (CI), stroke volume index (SVI)). mPAP and PAWP at baseline were neither associated with procedural success, immediate reduction of MR, nor residual MR after 6 months of follow-up. The composite outcome (All-cause mortality (ACM) and/or heart failure induced rehospitalization (HFH)) and HFH differed significantly after M-TEER when stratified according to mPAP, PAWP, PAPdia, a-wave and v-wave. ACM was not associated with the afore mentioned parameters. Neither PVR, TPG, CI nor SVI were associated with the composite outcome and HFH, respectively. In multivariable analyses, PAWP was independently associated with the composite outcome and HFH. PVR and SVI were not associated with outcomes. CONCLUSION: PAWP at baseline was significantly and independently associated with HFH and might serve as a valuable parameter for identifying patients at high risk for HFH after M-TEER. ACM and procedural success were not affected by pulmonary arterial pressure before M-TEER. We suggest that the post-capillary component of PH serves as the driving force behind the risk of HFH.

Cyclophilin A is a ligand for RAGE in thrombo-inflammation.

AIMS: Cyclophilin A (CyPA) induces leucocyte recruitment and platelet activation upon release into the extracellular space. Extracellular CyPA therefore plays a critical role in immuno-inflammatory responses in tissue injury and thrombosis upon platelet activation. To date, CD147 (EMMPRIN) has been described as the primary receptor mediating extracellular effects of CyPA in platelets and leucocytes. The receptor for advanced glycation end products (RAGE) shares inflammatory and prothrombotic properties and has also been found to have similar ligands as CD147. In this study, we investigated the role of RAGE as a previously unknown interaction partner for CyPA. METHODS AND RESULTS: Confocal imaging, proximity ligation, co-immunoprecipitation, and atomic force microscopy were performed and demonstrated an interaction of CyPA with RAGE on the cell surface. Static and dynamic cell adhesion and chemotaxis assays towards extracellular CyPA using human leucocytes and leucocytes from RAGE-deficient Ager-/- mice were conducted. Inhibition of RAGE abrogated CyPA-induced effects on leucocyte adhesion and chemotaxis in vitro. Accordingly, Ager-/- mice showed reduced leucocyte recruitment and endothelial adhesion towards CyPA in vivo. In wild-type mice, we observed a downregulation of RAGE on leucocytes when endogenous extracellular CyPA was reduced. We furthermore evaluated the role of RAGE for platelet activation and thrombus formation upon CyPA stimulation. CyPA-induced activation of platelets was found to be dependent on RAGE, as inhibition of RAGE, as well as platelets from Ager-/- mice showed a diminished activation and thrombus formation upon CyPA stimulation. CyPA-induced signalling through RAGE was found to involve central signalling pathways including the adaptor protein MyD88, intracellular Ca2+ signalling, and NF-κB activation. CONCLUSION: We propose RAGE as a hitherto unknown receptor for CyPA mediating leucocyte as well as platelet activation. The CyPA-RAGE interaction thus represents a novel mechanism in thrombo-inflammation.

Focal Pulsed Field Ablation for Atrial Arrhythmias: Efficacy and Safety under Deep Sedation.

Focal pulsed field ablation (PFA) is a novel technique for treating cardiac arrhythmias. It has demonstrated positive results in initial studies and has a good safety profile. In recent studies, PFA was often utilized for first-time pulmonary vein isolation (PVI) and was performed under general anesthesia. In our study, we assessed the feasibility, safety, acute procedural efficacy, and efficiency of focal PFA under deep sedation in patients, 80% of whom had undergone at least one left atrial ablation previously. We treated 30 patients (71 ± 7, 46% male) using the CENTAURI system for various atrial arrhythmias, including atrial fibrillation, typical and atypical atrial flutter, and focal atrial tachycardia. The average procedure and fluoroscopy times were 122 ± 43 min and 9 ± 7 min, respectively. A total of 83.33% of patients received additional line ablations beyond PVI, specifically targeting the posterior box and anterior mitral line. All ablations were successfully performed in deep sedation with only one major and one minor complication observed. The major complication was a vasospasm of the right coronary artery during ablation of the cavotricuspid isthmus, which was treated successfully with intracoronary nitroglycerin. All patients could be discharged in sinus rhythm. Moreover, adenosine appears effective in identifying dormant conduction in some patients after focal PFA. In conclusion, focal PFA is an effective approach for complex left atrial ablations under deep sedation, offering both high efficacy and efficiency with a reliable safety profile. Studies on long-term outcomes are needed.

Deceleration capacity of heart rate predicts 1-year mortality in patients undergoing transcatheter edge-to-edge mitral valve repair.

BACKGROUND: Risk stratification for transcatheter procedures in patients with severe mitral regurgitation is challenging. Deceleration capacity (DC) has already proven to be a reliable risk predictor in patients undergoing transcatheter aortic valve implantation. We hypothesized, that DC provides prognostic value in patients undergoing transcatheter edge-to-edge mitral valve repair (TEER). METHODS: We retrospectively analyzed electrocardiogram signals from 106 patients undergoing TEER at the University Hospital of Tübingen. All patients received continuous heart-rate monitoring to assess DC following the procedure. One-year all-cause mortality was defined as the primary end point. RESULTS: Sixteen patients (15.1%) died within 1 year. The DC in nonsurvivors was significantly reduced compared to survivors (5.1 ± 3.0 vs. 3.0 ± 1.6 ms, p = 0.002). A higher EuroSCORE II and impaired left ventricular function were furthermore associated with poor outcome. In Cox regression analyses, a DC < 4.5 ms was found a strong predictor of 1-year mortality (hazard ratio: 0.10, 95% confidence interval: 0.13-0.79, p = 0.029). Finally, a significant negative correlation was found between DC and residual mitral regurgitation after TEER (r = -0.41, p < 0.001). CONCLUSION: In patients with severe mitral regurgitation undergoing TEER, DC may serve as a new predictor of follow-up mortality.

Effect of Left Atrial Pulmonary Vein Angiography on Safety and Efficacy for High-Power, Short-Duration Pulmonary Vein Isolation in Patients with Atrial Fibrillation.

Imaging of pulmonary vein (PV) anatomy by angiography before pulmonary vein isolation (PVI) for atrial fibrillation (AF) has long been standard practice in many centers. Nowadays, very accurate anatomical maps can be generated by the use of high-resolution mapping catheters, and very effective ablation lesions can be generated by the use of the high-power, short-duration (HPSD) technique. In our center, PV angiography was routinely performed before PVI. However, since there is no clear evidence for this, we refrained from performing PV angiography. This study aimed to investigate whether PV angiography is still necessary when using high-resolution mapping catheters after ablation in the high-power, short-duration (HPSD) technique. A total of 139 consecutive patients with atrial fibrillation (66.25 ± 11.68 years old, 62.39% male) undergoing radiofrequency PVI were included in the study. Ablation was performed with the HPSD technique using a fixed protocol for energy delivery of 50 watts (contact force 3-20 g). We observed no significant effect on the efficacy, efficiency and complications of the ablation procedure if pulmonary vein angiography was omitted before HPSD PVI. Thus, using our protocol, it may be useful that PV angiography is avoided, especially in young patients and those with chronic renal disease.

[Tachycardiomyopathy]. / Tachykardiomyopathie.

Tachycardiomyopathy (TMP) is the development of heart failure due to a cardiac arrhythmia - triggered by rapid and/or irregular ventricular actions. TMP is in principle a (at least partially) reversible disease, so that control of the arrhythmia is of central importance. This article provides an overview of the causes, diagnosis and therapy.

High-resolution mapping as an alternative for exit block testing in the presence of entrance block after high-power short-duration pulmonary vein isolation.

BACKGROUND: After pulmonary vein isolation (PVI) for atrial fibrillation (AF), it is common as an endpoint to demonstrate an exit block from the pulmonary veins (PVs) in addition to an entrance block into them. By using high-resolution mapping catheters, even very small signals can be detected. OBJECTIVES: We investigated whether additional exit block testing is still necessary when using high-resolution mapping catheters after ablation in high-power short-duration (HPSD) techniques. MATERIALS AND METHODS: Overall, 114 patients with AF (average age, 65.14 ± 11.3 years; 65.8% male) undergoing radiofrequency PVI were included in the study. Ablation was performed with the HPSD technique using a fixed protocol for energy delivery of 50 W (contact force 3-20 g). Entrance and exit block were tested with a high-resolution mapping catheter. Isolation of the PVs was achieved in all patients. RESULTS: Capture of local PV tissue was demonstrated in all patients after PVI and exit block was present in all patients after entrance block was detected using a high-resolution mapping catheter. CONCLUSION: Exit block testing in addition to the demonstration of an entrance block as an endpoint of PVI seems to have no additional benefit and might no longer be necessary when a high-resolution mapping catheter is used in HPSD ablation for PVI of AF.

Novel ventricular tachyarrhythmia detection enhancement detects undertreated life-threatening arrhythmias.

BACKGROUND: Ventricular tachyarrhythmias (VTA) with low and varying signal amplitudes and morphologies may not be successfully identified utilizing traditional implantable cardioverter-defibrillator algorithms. OBJECTIVE: Develop and validate a novel algorithm (VF Therapy Assurance, VFTA) to improve detection and timely delivery of high-voltage therapy (HVT) for these arrhythmias. METHODS: Arrhythmia detection was simulated on recorded VTA electrograms (EGMs) utilizing Abbott's Merlin.net database. EGMs where an HVT occurred only when VFTA was enabled, or where VFTA provided an HVT >30 seconds earlier than without VFTA, were readjudicated with physician review. As VFTA never prevents detection or therapy, EGMs where VFTA did not activate or alter HVT were not adjudicated. RESULTS: Among 564,353 recorded VTA EGMs from 20,000 devices, VFTA altered HVT in 105 EGMs from 67 devices. Physician adjudication determined that 81.9% (86/105) of these EGMs were true undertreated VTA episodes and would have received appropriate HVT with VFTA enabled. Furthermore, 65% of the episodes (56/86) were ventricular fibrillation, were polymorphic, did not self-terminate during the recording window, or were not amenable antitachycardia pacing. Of those, 87.5% (49/56) would not have elicited HVT without VFTA. Overall, VFTA provided new or earlier appropriate HVT in 0.27% (53/20,000) of devices with an increase in inappropriate HVT in 0.07% (14/20,000) devices. CONCLUSION: The VFTA algorithm successfully identifies VTA missed by traditional detection algorithms, owing to undersensed ventricular signals resulting in the rate falling below the programmed detection rate. The use of VFTA increases the likelihood of delivering life-saving HVT.

Cyclophilin A Is Not Acetylated at Lysine-82 and Lysine-125 in Resting and Stimulated Platelets.

Cyclophilin A (CyPA) is widely expressed by all prokaryotic and eukaryotic cells. Upon activation, CyPA can be released into the extracellular space to engage in a variety of functions, such as interaction with the CD147 receptor, that contribute to the pathogenesis of cardiovascular diseases. CyPA was recently found to undergo acetylation at K82 and K125, two lysine residues conserved in most species, and these modifications are required for secretion of CyPA in response to cell activation in vascular smooth muscle cells. Herein we addressed whether acetylation at these sites is also required for the release of CyPA from platelets based on the potential for local delivery of CyPA that may exacerbate cardiovascular disease events. Western blot analyses confirmed the presence of CyPA in human and mouse platelets. Thrombin stimulation resulted in CyPA release from platelets; however, no acetylation was observed-neither in cell lysates nor in supernatants of both untreated and activated platelets, nor after immunoprecipitation of CyPA from platelets. Shotgun proteomics detected two CyPA peptide precursors in the recombinant protein, acetylated at K28, but again, no acetylation was found in CyPA derived from resting or stimulated platelets. Our findings suggest that acetylation of CyPA is not a major protein modification in platelets and that CyPA acetylation is not required for its secretion from platelets.

"Mind the Gap": An 85-Year-Old Man with Severe Tricuspid Valve Regurgitation Who Underwent Percutaneous Edge-to-Edge Valve Leaflet Plication Using the New and Advanced MitraClip XTR System.

BACKGROUND Severe tricuspid valve regurgitation (TR) is associated with high cardiovascular mortality. Safe and feasible interventional approaches to treat severe TR are of clinical relevance. The MitraClip is a device that has been approved by the US Food and Drug Administration (FDA) for the repair of mitral valve lesions. Percutaneous femoral venous access with fluoroscopic and echocardiographic guidance is used to deliver a cobalt-chromium clip to secure the mitral valve leaflets. We report on an 85-year-old man with tricuspid valve regurgitation who underwent percutaneous edge-to-edge tricuspid valve leaflet plication with the new, advanced MitraClip XTR System. CASE REPORT An 85-year-old man with severe TR due to annulus dilation of the right ventricle and short septal leaflet presented repeatedly at our hospital with severe right heart failure symptoms. Transesophageal echocardiography revealed severe TR with a large coaptation gap size of 10.6 mm. Percutaneous edge-to-edge valve repair with the new-generation MitraClip System XTR with wider clip arms could overcome the large coaptation gap. We achieved a strong reduction of TR after deploying 2 MitraClips XTR. The patient recovered quickly and has not been admitted to hospital due to heart failure symptoms since the intervention for more than 6 months. CONCLUSIONS Previous studies have shown the safety and effectiveness of the MitraClip device and supported FDA approval for tricuspid valve repair. This report of a patient with complex tricuspid regurgitation demonstrated the feasible use of the new MitraClip XTR System, which improved edge-to-edge tricuspid valve repair due to its increased span and improved grip.

The aged hematopoietic system promotes hippocampal-dependent cognitive decline.

The aged systemic milieu promotes cellular and cognitive impairments in the hippocampus. Here, we report that aging of the hematopoietic system directly contributes to the pro-aging effects of old blood on cognition. Using a heterochronic hematopoietic stem cell (HSC) transplantation model (in which the blood of young mice is reconstituted with old HSCs), we find that exposure to an old hematopoietic system inhibits hippocampal neurogenesis, decreases synaptic marker expression, and impairs cognition. We identify a number of factors elevated in the blood of young mice reconstituted with old HSCs, of which cyclophilin A (CyPA) acts as a pro-aging factor. Increased systemic levels of CyPA impair cognition in young mice, while inhibition of CyPA in aged mice improves cognition. Together, these data identify age-related changes in the hematopoietic system as drivers of hippocampal aging.

Predictors of Mortality in Patients With Biopsy-Proven Viral Myocarditis: 10-Year Outcome Data.

Background There is scarce data about the long-term mortality as well as the prognostic value of cardiovascular magnetic resonance and late gadolinium enhancement (LGE) in patients with biopsy-proven viral myocarditis. We sought to investigate: (1) mortality and (2) prognostic value of LGEcardiovascular magnetic resonance (location, pattern, extent, and distribution) in a >10-year follow-up in patients with biopsy-proven myocarditis. Methods and Results Two-hundred three consecutive patients with biopsy-proven viral myocarditis and cardiovascular magnetic resonance were enrolled; 183 patients were eligible for standardized follow-up. The median follow-up was 10.1 years. End points were all-cause death, cardiac death, and sudden cardiac death (SCD). We found substantial long-term mortality in patients with biopsy-proven myocarditis (39.3% all cause, 27.3% cardiac, and 10.9% SCD); 101 patients (55.2%) demonstrated LGE. The presence of LGE was associated with a more than a doubled risk of death (hazard ratio [HR], 2.40; 95% CI], 1.30-4.43), escalating to a HR of 3.00 (95% CI, 1.41-6.42) for cardiac death, and a HR of 14.79 (95% CI, 1.95-112.00) for SCD; all P≤0.009. Specifically, midwall, (antero-) septal LGE, and extent of LGE were highly associated with death, all P<0.001. Septal LGE was the best independent predictor for SCD (HR, 4.59; 95% CI, 1.38-15.24; P=0.01). Conclusions In patients with biopsy-proven viral myocarditis, the presence of midwall LGE in the (antero-) septal segments is associated with a higher rate of mortality (including SCD) compared with absent LGE or other LGE patterns, underlining the prognostic benefit of a distinct LGE analysis in these patients.

CD147 is a Novel Interaction Partner of Integrin αMß2 Mediating Leukocyte and Platelet Adhesion.

Surface receptor-mediated adhesion is a fundamental step in the recruitment of leukocytes and platelets, as well as platelet-leukocyte interactions. The surface receptor CD147 is crucially involved in host defense against self-derived and invading targets, as well as in thrombosis. In the current study, we describe the previously unknown interaction of CD147 with integrin αMß2 (Mac-1) in this context. Using binding assays, we were able to show a stable interaction of CD147 with Mac-1 in vitro. Leukocytes from Mac-1-/- and CD147+/- mice showed a markedly reduced static adhesion to CD147- and Mac-1-coated surfaces, respectively, compared to wild-type mice. Similarly, we observed reduced rolling and adhesion of monocytes under flow conditions when cells were pre-treated with antibodies against Mac-1 or CD147. Additionally, as assessed by antibody inhibition experiments, CD147 mediated the dynamic adhesion of platelets to Mac-1-coated surfaces. The interaction of CD147 with Mac-1 is a previously undescribed mechanism facilitating the adhesion of leukocytes and platelets.

Platelet surface expression of cyclophilin A is associated with increased mortality in patients with symptomatic coronary artery disease.

BACKGROUND: Cyclophilin A (CyPA) is an important intracellular molecule mediating essential cellular functions such as signaling and protein folding. Enhanced CyPA platelet surface expression is associated with hypertension and hypercholesterolemia in patients with stable coronary artery disease (CAD). In patients with acute myocardial infarction CyPA platelet surface expression is significantly decreased. The aim of this study was to investigate possible associations of CyPA platelet surface expression and a clinically relevant CyPA single-nucleotide polymorphism (CyPA PPIA rs6850) with prognosis in patients with symptomatic cardiovascular disease. MATERIALS AND METHODS: Blood was obtained from 335 consecutive patients with symptomatic CAD. All patients were followed up for 1080 days for endpoints all-cause death, myocardial infarction (MI), ischemic stroke, and bleeding. The primary combined endpoint was defined as a composite of all-cause death and/or MI and/or ischemic stroke. Cyclophilin A platelet surface expression levels less than or equal to the median were significantly associated with a worse prognosis (combined endpoint and all-cause death) when compared to CyPA greater than the median. Genotyping for CyPA PPIA rs6850 was performed in 752 patients with symptomatic CAD. Homozygous carriers of the minor allele showed a significantly worse cumulative event-free survival for both combined endpoint and MI when compared to carriers of the major allele. CONCLUSION: The CyPA platelet surface expression is associated with mortality whereas CyPA PPIA rs6850 is associated with recurrent MI in patients with symptomatic CAD. Cyclophilin A might offer a new biomarker for risk stratification and tailoring therapies in patients with cardiovascular disease.

Pivotal role of PDK1 in megakaryocyte cytoskeletal dynamics and polarization during platelet biogenesis.

During thrombopoiesis, megakaryocytes (MKs) form proplatelets within the bone marrow (BM) and release platelets into BM sinusoids. Phosphoinositide-dependent protein kinase-1 (PDK1) is required for Ca2+-dependent platelet activation, but its role in MK development and regulation of platelet production remained elusive. The present study explored the role of PDK1 in the regulation of MK maturation and polarization during thrombopoiesis using a MK/platelet-specific knockout approach. Pdk1-deficient mice (Pdk1-/-) developed a significant macrothrombocytopenia as compared with wild-type mice (Pdk1fl/fl). Pdk1 deficiency further dramatically increased the number of MKs without sinusoidal contact within the BM hematopoietic compartment, resulting in a pronounced MK hyperplasia and a significantly increased extramedullary thrombopoiesis. Cultured Pdk1-/- BM-MKs showed impaired spreading on collagen, associated with an altered actin cytoskeleton structure with less filamentous actin (F-actin) and diminished podosome formation, whereas the tubulin cytoskeleton remained unaffected. This phenotype was associated with abrogated phosphorylation of p21-activated kinase (PAK) as well as its substrates LIM domain kinase and cofilin, supporting the hypothesis that the defective F-actin assembly results from increased cofilin activity in Pdk1-deficient MKs. Pdk1-/- BM-MKs developed increased ploidy and exhibited an abnormal ultrastructure with disrupted demarcation membrane system (DMS). Strikingly, Pdk1-/- BM-MKs displayed a pronounced defect in DMS polarization and produced significantly less proplatelets, indicating that PDK1 is critically required for proplatelet formation. In human MKs, genetic PDK1 knockdown resulted in increased maturity but reduced platelet-like particles formation. The present observations reveal a pivotal role of PDK1 in the regulation of MK cytoskeletal dynamics and polarization, proplatelet formation, and thrombopoiesis.

Conventional echocardiographic parameters or three-dimensional echocardiography to evaluate right ventricular function in percutaneous edge-to-edge mitral valve repair (PMVR).

INTRODUCTION: In this study, we evaluated right ventricular (RV) function before and after percutaneous mitral valve repair (PMVR) using conventional echocardiographic parameters and novel 3DE data sets acquired prior to and directly after the procedure. PATIENTS AND METHODS: Observational study on 45 patients undergoing PMVR at an university hospital. RESULTS: In the overall collective, the 3D RV-EF before and after PMVR showed no significant change (p = 0.16). While there was a significant increase of the fractional area change (FAC, from 23 [19-29] % to 28 [24-33] %, p = 0.001), no significant change of the tricuspid annular plane systolic excursion (TAPSE, from 17 ±â€¯6 mm to 18 ±â€¯5 mm (standard deviation), p = 0.33) was observed. Regarding patients with a reduced RV-EF (< 35%), a significant RV-EF improvement was observed (from 27 [23-34] % to 32.5 [30-39] % (p = 0.001). 71.4% of patients had an improved clinical outcome (improvement in 6-minute walk test and/or improvement in NYHA class of more than one grade), whereas clinical outcome did not improve in 28.6% of patients. Using univariate logistic regression analysis, the post-PMVR RV-EF (OR 1.15: 95% CI 1.02-1.29; p = 0.02) and the change in RV-EF (OR 1.13: 95% CI 1.02-1.25; p = 0.02) were significant predictors for improved clinical outcome at 6 months follow up. CONCLUSION: Thus, RV function may be an important non-invasive parameter to add to the predictive parameters indicating a potential clinical benefit from treatment of severe mitral regurgitation using PMVR.

ECG changes after percutaneous edge-to-edge mitral valve repair.

BACKGROUND: Mitral regurgitation (MR) has a severe impact on hemodynamics and induces severe structural changes in the left atrium. Atrial remodeling is known to alter excitability and conduction in the atrium facilitating atrial fibrillation and atrial flutter. PMVR is a feasible and highly effective procedure to reduce MR in high-risk patients, which are likely to suffer from atrial rhythm disturbances. So far, electroanatomical changes after PMVR have not been studied. HYPOTHESIS: In the current study, we investigated changes in surface electrocardiograms (ECGs) of patients undergoing PMVR for reduction of MR. METHODS: We evaluated 104 surface ECGs from patients in sinus rhythm undergoing PMVR. P wave duration, P wave amplitude, PR interval, QRS duration, QRS axis, and QT interval were evaluated before and after PMVR and at follow-up. RESULTS: We found no changes in QRS duration, QRS axis, and QT interval after successful PMVR. However, P wave duration, amplitude, and PR interval were significantly decreased after reduction of MR through PMVR (P < .05, respectively). CONCLUSION: The data we provide offers insight into changes in atrial conduction after reduction of MR using PMVR in patients with sinus rhythm.

Thrombogenicity and Antithrombotic Strategies in Structural Heart Interventions and Nonaortic Cardiac Device Therapy-Current Evidence and Practice.

As the number of, and the indications for, structural heart interventions are increasing worldwide, the optimal secondary prevention to reduce device thrombosis is becoming more important. To date, most of the recommendations are empiric. The current review discusses mechanisms behind device-related thrombosis, the available evidence with regard to antithrombotic regimen after cardiac device implantation, as well as providing an algorithm for identification of risk factors for device thrombogenicity and for management of device thrombosis after implantation of patent foramen ovale and left atrial appendage occluders, MitraClips/transcatheter mitral valve replacement, pacemaker leads, and left ventricular assist devices. Of note, the topic of antithrombotic therapy and thrombogenicity of prostheses in aortic position (transcatheter aortic valve replacement, surgical, mechanical, and bioprostheses) is not part of the present article and is discussed in detail in other contemporary focused articles.