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Background: Mid-term comparative data for the self-expanding ACURATE neo2 transcatheter heart valve and the balloon-expandable SAPIEN 3 Ultra are lacking., Objectives: The aim of this study was to compare 1-year outcomes after transcatheter aortic valve replacement of these 2 valves., Methods: A total of 2,106 patients from 3 centers (neo2, n = 1,166; Ultra, n = 940) undergoing transfemoral transcatheter aortic valve replacement were analyzed retrospectively. The primary endpoint was the composite of all-cause mortality, stroke, and rehospitalization at 1 year. Secondary endpoints were the individual components of the primary endpoint at 1 year. To adjust for baseline differences, nearest neighbor propensity score matching was used., Results: After matching (702 pairs), baseline characteristics were similar between groups. Device success was more common in the neo2 group (87.5% vs 82.3%; P = 0.007), irrespective of matching. DP mean after the procedure was higher for Ultra (13 mm Hg [Q1-Q3: 10-15 mm Hg] vs 8 mm Hg [Q1-Q3: 6-11] mm Hg; P < 0.001). Rates of paravalvular leakage, device embolization, and multiple valve implantations were more common in the neo2 arm, whereas major cardiac structural complications and major vascular complications occurred more frequently in the Ultra group. All other in-hospital complication rates were similar between the 2 groups. At 1 year, the cumulative incidence of the primary endpoint (14.1% for neo2 vs 14.5% for Ultra; P = 0.819) was similar between the groups. Likewise, the individual components showed no difference between the groups., Conclusions: Despite differing immediate results, the outcomes at 1 year, including the composite of all-cause mortality, stroke, or hospitalization, were similar for neo2 and Ultra transcatheter heart valves., Competing Interests: Funding Support and Author Disclosures Dr Kim has received proctor and/or speaker and/or advisory honoraria from Abbott, Boston Scientific, Edwards Lifesciences, Meril Life Sciences, Shockwave, and HID Imaging. Dr Choi has received speaker and proctor fees from Edwards Lifesciences, CytoSorbents, and Getinge. Dr Charitos is a proctor for Boston Scientific. Dr Rheude has received lecture fees from Abbott, AstraZeneca, SIS Medical, and Translumina; and has received travel support from Boston Scientific and Eli Lilly (not related to the present work). Dr Joner has received lecture fees and research grants from Edwards Lifesciences and Boston Scientific; and is a consultant for Biotronik and OrbusNeich. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In addition to the edge-to-edge MitraClip repair system, the edge-to-spacer PASCAL repair system was approved for percutaneous treatment of severe mitral regurgitation (MR). Comparative data are lacking., Objectives: The aim of this study was to compare procedural and short-term safety and efficacy of 2 leaflet-based transcatheter mitral valve repair systems., Methods: Procedural and 30-day outcomes were investigated in a propensity score-matched cohort of 307 PASCAL and 307 MitraClip patients at 10 sites. Matching criteria included sex, age, left ventricular ejection fraction, New York Heart Association functional class, MR etiology, left ventricular end-diastolic diameter, left atrial volume index, and vena contracta width. The primary efficacy endpoints were technical success and degree of residual MR at discharge. The primary safety endpoint was the rate of major adverse events (MAE)., Results: Technical success was 97.0% in the PASCAL group and 98.0% in the MitraClip group (P = 0.624). MR ≤2+ at discharge was comparable in both groups (PASCAL: 93.8% vs MitraClip: 92.4%; P = 0.527), with more patients exhibiting MR ≤1+ in the PASCAL group (70.5% vs 56.6%; P < 0.001). The postprocedural mean gradient was significantly higher in the MitraClip group (3.3 ± 1.5 mm Hg vs 3.9 ± 1.7 mm Hg; P < 0.001). At 30 days, all-cause mortality and MAE rates were similar (mortality: 1.7% vs 3.3%; P = 0.299; MAE: 3.9% vs 5.2%; P = 0.562)., Conclusions: In this first large propensity score-matched comparison, procedural success rates and MAE did not differ significantly between patients treated with the PASCAL or MitraClip valve repair system. Procedural results with less than moderate MR and no elevated transmitral gradient were more common in the PASCAL group, which might have an impact on long-term outcome., Competing Interests: Funding Support and Author Disclosures Dr Iliadis has received travel support from Abbott; and has received consultant honoraria from Abbott and Edwards Lifesciences. Dr Hausleiter has received research grants and speaker honoraria from Abbott Cardiovascular and Edwards Lifesciences. Dr Lurz has received institutional fees and research grants from Abbott Cardiovascular, Edwards Lifesciences, and Medtronic. Dr Möllmann has received speaker honoraria from Abbott Cardiovascular and Edwards Lifesciences. Dr Rudolph has received research grants and consulting honoraria from Edwards Lifesciences. Dr von Bardeleben has received consulting and lecture honoraria from Abbott Cardiovascular, Boehringer Ingelheim, Edwards Lifesciences, NeoChord, and Medtronic. Dr Nef has received speaker and consulting honoraria from Abbott Vascular and Edwards Lifesciences. Dr Luedike has received consulting and lecture honoraria from Edwards Lifesciences. Drs Pfister and Baldus have received consulting honoraria from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to investigate the procedural and short-term safety and efficacy of a new leaflet-based transcatheter mitral valve repair system., Background: The PASCAL repair system has been recently approved for percutaneous treatment of mitral regurgitation (MR). Novel characteristics are broad paddles positioned around a central spacer and the ability for independent leaflet capture., Methods: Procedural and 30-day outcomes were investigated in the first 309 patients with symptomatic MR 3+/4+ treated with the PASCAL repair system at 10 sites. Primary efficacy endpoints were technical success and degree of residual MR at discharge. The primary safety endpoint was the rate of major adverse events (MAE)., Results: Among the 309 patients (mean age 77 ± 10 years, 42% women, mean European System for Cardiac Operative Risk Evaluation II score 5.8 ± 4.5%) included in this study, MR etiology was degenerative in 33%, functional in 52%, and mixed in 16%. Eighty-six percent of patients were in New York Heart Association functional class III or IV. The technical success rate was 96%. Of 308 patients discharged alive, MR was ≤2+ in 93.5%. At 30 days, the MAE rate was 4.1%, with an estimated all-cause mortality rate of 2.0%, and 72% of patients were in New York Heart Association functional class ≤II (p < 0.001). Rates of device success and CLASP (Edwards PASCAL Transcatheter Mitral Valve Repair System Study) trial-defined clinical success were 81.9% and 86.9%, respectively. Single-leaflet device attachment occurred in 7 patients (2.3%)., Conclusions: Mitral valve repair with the PASCAL system in the early post-approval phase was effective and safe, with high procedural success rates and low rates of MAE. MR was significantly reduced, accompanied by significant improvement in functional status., Competing Interests: Author Disclosures Drs. Pfister and Baldus have received honoraria for consulting from Edwards Lifesciences. Dr. Luedike has received honoraria for consulting and lectures from Edwards Lifesciences. Dr. Rudolph has received research grants and honoraria for consulting from Edwards Lifesciences. Dr. Hausleiter has received research grants and speaking honoraria from Abbott Cardiovascular and Edwards Lifesciences. Dr. Lurz has received institutional fees and research grants from Abbott Cardiovascular, Edwards Lifesciences, and Medtronic. Dr. Nef has received speaking and consulting honoraria from Abbott Vascular and Edwards Lifesciences. Dr. Möllmann has received speaking honoraria from Abbott Cardiovascular and Edwards Lifesciences. Dr. von Bardeleben has received consulting and lecture honoraria from Abbott Cardiovascular, Boehringer Ingelheim, Cardiac Dimensions, and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We wanted to explore the effects of two different low doses (0.5μM and 0.05μM) of mifepristone, exposed during the receptive period, on the human embryo implantation process, using a well-established three-dimensional in vitro cell culture model, specifically developed to study this process., Methods: An in vitro three-dimensional cell culture model was constructed using human endometrial cells isolated from the endometrium of proven fertile women, collected on cycle day LH+4. After 5 days of culture, supernumerary human embryos were added and cultured for another 5 days with mifepristone 0.5μM (n=8) or 0.05μM (n=10) or vehicle as control (n=10). The cultures were checked for embryo attachment and terminated. We studied the expression of 16 reported endometrial receptivity markers in the endometrial constructs using real-time polymerase chain reaction., Results: None of the embryos in 0.5μM of mifepristone attached to the endometrial constructs (p=.004), whereas 4 out of 10 in 0.05μM (p=.3698) and 7 out of 10 embryos in the control group attached to the cultures. We found that most of the studied receptivity markers were significantly altered with mifepristone exposure in a similar direction in both treatment groups. Only IL6 was significantly differentially expressed between the treatment groups (p=.017)., Conclusion: We report for the first time that exposure to a low concentration (0.5μM) of mifepristone during the receptive period successfully inhibits human embryo implantation process in vitro. Further, we observed a dose-dependent effect of mifepristone on endometrial receptivity at the functional level., Implication: This study contributes new knowledge that low dose of mifepristone during the short period of receptive phase can inhibit endometrial receptivity, which further promotes mifepristone as a contraceptive agent. This could give women a treatment choice to avoid unwanted pregnancy with high efficacy and minimal side effects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Acute type A aortic dissection (AAD) is a life-threatening disorder with a high rate of mortality and complications. All cannulation techniques currently used to establish arterial flow for cardiopulmonary bypass are associated with a considerable risk of organ malperfusion, stroke, or access site trauma. Here, we report the impact of transatrial cannulation of the left ventricle on patient outcome after surgical treatment of AAD., Methods: Between 2010 and 2013, 46 patients underwent emergency surgery for AAD using transatrial cannulation of the left ventricle. Their outcome was retrospectively compared with that of 73 age- and sex-matched patients operated on for AAD between 2006 and 2010 before introduction of the new technique., Results: No differences concerning preoperative details were found. Arterial flow before 2010 was established after preparation of the femoral artery in 46 patients (63.0%) or by direct cannulation of the ascending aorta in 27 patients (37.0%). Operation times were significantly lower in the transatrial cannulation group (271.2 ± 75.4 versus 308.3 ± 78.2; p = 0.02). Postoperatively, we observed a significantly reduced stroke rate in the group with transatrial cannulation (6.5% versus 26.5%; p = 0.007) and a decreased rate of acute renal failure (20.0% versus 32.4%; p = 0.003). Intraoperative mortality (0% versus 6.8%; p = 0.16), 30-day mortality (8.9% versus 10.3%; p = 1.00), and mortality during follow-up (9.8% versus 34.4%; p = 0.08) did not differ. However, overall mortality was significantly lower in the group after transatrial cannulation (17.7% versus 45.2%; p = 0.003)., Conclusions: In patients undergoing surgery for AAD, transatrial cannulation of the left ventricle proved to be a safe and easy cannulation method that significantly reduced postoperative complications., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Toll-like receptors (TLRs) are known primarily as pathogen recognition receptors of the innate immunity, initiating inflammatory pathways to organize the immune defense. More recently, an involvement of TLRs in various physiologic and pathologic processes has been reported. Because many of these processes implicate angiogenesis, we here elucidated the role of a TLR2/6-dependent pathway on angiogenesis using the TLR2/6 agonist macrophage-activating lipopeptide of 2 kDa (MALP-2), a common bacterial lipopeptide. In vivo and in vitro Matrigel assays demonstrated that MALP-2 promoted angiogenesis in a TLR2/6-dependent manner. Moreover, MALP-2 induced endothelial cell proliferation and migration and a strong secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF release in response to MALP-2 from isolated vascular segments was completely prevented when the endothelium was removed. MALP-2 containing Matrigel implants exhibited vascular structures as well as CD45(+) cells. MALP-2 induced migration of leukocytes and likewise GM-CSF release, particularly from the monocyte population. Inhibition of GM-CSF by siRNA or antibodies suppressed MALP-2-induced angiogenesis in vitro and in vivo. These results clearly identified a TLR2/6-dependent induction of angiogenesis by the bacterial lipopeptide MALP-2, which is mediated by GM-CSF. This might represent a general mechanism to enhance or restore blood flow and recruit immune cells for pathogen defense and tissue regeneration.

Therapeutic strategies to prevent atherosclerotic plaque progression and achieve plaque stabilization involve 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)-reductase inhibitors (statins) and renin-angiotensin system (RAS)-blockade, but studies investigating the potentially additive effects of a combined treatment strategy are rare. We hypothesised that the adjunction of atorvastatin with telmisartan or ramipril might achieve additional effects on experimental atherosclerosis though statin-induced lipid-lowering is lacking. ApoE-/- mice were fed a high-fat diet for 12 weeks and randomized to either placebo (CON), atorvastatin (ATO), ramipril (RAM), telmisartan (TEL) or RAM+ATO and TEL+ATO (N=23 per group). RAS-blockade, but not ATO, reduced systolic blood pressure. None of the treatment regimens lowered systemic cholesterol levels or lipoprotein fractions. RAM, TEL and the combined therapy, but not ATO, significantly reduced aortic lipid deposition. All substances significantly reduced monocyte chemoattracting protein (MCP)-1 concentrations, macrophages and matrixmetalloproteinase (MMP)-9 content and enhanced plaque's content of tissue inhibitor of MMP (TIMP)-1, collagen and fibrous cap thickness, resulting in an overall decrease of advanced plaques (classified as types IV-VI). Additive effects of the adjunction were observed on MMP-9 gelatinolytic activity, interleukin (IL)-6 and IL-10 plasma levels. These results indicate that a combined treatment with RAS-blockade and statins may have additive effects on systemic cardiovascular risk markers even in the absence of lipid-reduction, although additional effects on atherosclerotic plaque progression and stability were not observed in this model.

Activated matrix metalloproteinases (MMPs) in patients with acute coronary syndromes may contribute to plaque destabilization. Since reactive oxygen species (ROS) induce MMP-2 and angiotensin II (ANG II) enhances NADPH-oxidase-dependent ROS formation, we assessed whether ANG II induces MMP-2 in a NADPH-oxidase-dependent manner. MMP-2 mRNA expression and activity were analyzed in wildtype and p47phox-deficient (p47phox-/-) murine smooth muscle cells (SMC). To address a clinical implication, sections of human atherosclerotic arteries were stained for MMP-2, p47phox, ANG II, AT1-receptor, and alpha-smooth muscle cell actin (alpha-SMC actin). MMP-2 protein expression and activity from these arteries were compared to those without atherosclerosis. ANG II enhances mRNA synthesis and activity of MMP-2 in a p47phox-dependent manner. Immunohistochemical analyses revealed a co-localization of MMP-2 with p47phox, ANG II, AT1-receptor, and alpha-SMC actin. MMP-2 protein expression and gelatinolytic activity are increased in atherosclerotic arteries. Thus, activation of the renin-angiotensin system may contribute to plaque destabilization via ROS-dependent induction of MMP-2.