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Background: To date, the only effective treatment of severe aortic stenosis is valve replacement. With the introduction of transcatheter aortic valve replacement and extending indications to younger patients, the use of bioprosthetic valves (BPVs) has considerably increased. The main inconvenience of BPVs is their limited durability because of mechanisms similar as the fibro-calcifying processes observed in native aortic stenosis. One of the major gaps of the field is to identify therapeutic targets to prevent or slow the fibro-calcifying process leading to severe and symptomatic aortic stenosis. The aim was to identify new targets for anticalcification drugs to prevent aortic and BPV calcification using an unbiased translational approach., Methods: Explanted valves were collected from patients and organ donor hearts. A comparative transcriptomic analysis was performed on valvular interstitial cells (VIC) obtained from calcified (bicuspid and tricuspid) versus control valves. The mechanisms and consequences of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) downregulation were analyzed in VIC cultures from control human aortic valves. ALDH1A1 was inhibited or silenced and its impact on osteogenic marker expression and calcification processes assessed in VIC. The effect of all-trans retinoic acid on calcification was tested on human VIC cultures and on 2 animal models: the model of subcutaneous implantation of bovine pericardium in rats and the model of xenograft aortic valve replacement in juvenile sheep., Results: Transcriptome analysis of human VIC identified ALDHA1 as the most downregulated gene in VIC from calcified versus control valves. In human VIC, ALDH1A1 expression is downregulated by TGF-β1 in a SMAD2/3-dependent manner. ALDH1A1 inhibition promotes an osteoblast-like VIC phenotype and increases calcium deposition through inhibition of retinoic acid receptor alpha signaling. Conversely, VIC treatment with retinoids decreases calcium deposition and attenuates VIC osteoblast activity. Last, all-trans retinoic acid inhibits calcification development of aortic BPV in both in vivo models and improves aortic valve echocardiographic parameters in the xenograft sheep model., Conclusions: These results show that ALDH1A1 is downregulated in calcified valves, hence promoting VIC transition into an osteoblastic phenotype. Retinoic acid receptor alpha agonists, including all-trans retinoic acid through a drug repositioning strategy, represent a promising and innovative pharmacological approach to prevent calcification of native aortic valves and BPV.

We report the case of a redo Ross surgery complicated by an ostial left circumflex occlusion requiring emergent percutaneous coronary intervention. The latter was complicated by coronary perforation treated by two covered stents with V-stenting technique. After immediate success, the clinical course was marked by acute stent thrombosis requiring emergent coronary bypass., Learning Objectives: Ostial left circumflex perforation is a rare and potentially fatal complication that is challenging to manage. V stenting technique with two covered stents could be used as a life-saving procedure, but is associated with a high thrombotic risk., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Both computed tomography (CT) angiography and vascular ultrasound have a major role before and during a transfemoral approach to TAVR. CT angiography will determine whether the patient is eligible for a femoral approach. Peri-procedural arterial ultrasound will be helpful to improve safety and optimize results during the femoral approach. Being able to interpret both of these imaging modalities is of paramount importance for any interventional cardiologist who practices structural interventions., (Copyright © 2022. Published by Elsevier Masson SAS.)

Background: Cerebral microbleeds (CMBs) have been observed in healthy elderly people undergoing systematic brain magnetic resonance imaging. The potential role of acute triggers on the appearance of CMBs remains unknown. We aimed to describe the incidence of new CMBs after transcatheter aortic valve replacement (TAVR) and to identify clinical and procedural factors associated with new CMBs including hemostatic measures and anticoagulation management., Methods: We evaluated a prospective cohort of patients with symptomatic aortic stenosis referred for TAVR for CMBs (METHYSTROKE [Identification of Epigenetic Risk Factors for Ischemic Complication During the TAVR Procedure in the Elderly]). Standardized neurologic assessment, brain magnetic resonance imaging, and analysis of hemostatic measures including von Willebrand factor were performed before and after TAVR. Numbers and location of microbleeds on preprocedural magnetic resonance imaging and of new microbleeds on postprocedural magnetic resonance imaging were reported by 2 independent neuroradiologists blinded to clinical data. Measures associated with new microbleeds and postprocedural outcome including neurologic functional outcome at 6 months were also examined., Results: A total of 84 patients (47% men, 80.9±5.7 years of age) were included. On preprocedural magnetic resonance imaging, 22 patients (26% [95% CI, 17%-37%]) had at least 1 microbleed. After TAVR, new microbleeds were observed in 19 (23% [95% CI, 14%-33%]) patients. The occurrence of new microbleeds was independent of the presence of microbleeds at baseline and of diffusion-weighted imaging hypersignals. In univariable analysis, a previous history of bleeding ( P =0.01), a higher total dose of heparin ( P =0.02), a prolonged procedure ( P =0.03), absence of protamine reversion ( P =0.04), higher final activated partial thromboplastin time ( P =0.05), lower final von Willebrand factor high-molecular-weight:multimer ratio ( P =0.007), and lower final closure time with adenosine-diphosphate ( P =0.02) were associated with the occurrence of new postprocedural microbleeds. In multivariable analysis, a prolonged procedure (odds ratio, 1.22 [95% CI, 1.03-1.73] for every 5 minutes of fluoroscopy time; P =0.02) and postprocedural acquired von Willebrand factor defect (odds ratio, 1.42 [95% CI, 1.08-1.89] for every lower 0.1 unit of high-molecular-weight:multimer ratio; P =0.004) were independently associated with the occurrence of new postprocedural microbleeds. New CMBs were not associated with changes in neurologic functional outcome or quality of life at 6 months., Conclusions: One out of 4 patients undergoing TAVR has CMBs before the procedure and 1 out of 4 patients develops new CMBs. Procedural or antithrombotic management and persistence of acquired von Willebrand factor defect were associated with the occurrence of new CMBs., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02972008.

Background: Balloon aortic valvuloplasty (BAV) has been proposed as a therapeutic option in patients suffering from severe aortic stenosis (SAS) who need urgent non-cardiac surgery (NCS). Whether this strategy is better than medical therapy in this very specific population is unknown., Aims: We aimed to evaluate the clinical benefit of an invasive strategy (IS) with preoperative BAV in patients with SAS requiring urgent NCS., Methods: From 2011 to 2019, a registry conducted in two centres included 133 patients with SAS undergoing urgent NCS, of whom 93 underwent preoperative BAV (IS) and 40 a conservative strategy (CS) without BAV. All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW) (10 clinical and anatomical variables)., Results: The primary outcome was MACE at one-month follow-up after NCS including mortality, heart failure, and other cardiovascular outcomes. In patients managed conservatively, occurrence of MACE was 20.0% (n=8) and death was 10.0% (n=4) at 1 month. In patients undergoing BAV, the occurrence of MACE was 20.4% (n=19) and death was 5.4% (n=5) at 1 month. Among patients undergoing conservative management, all events were observed after NCS while, in patients undergoing BAV, 12.9% (n=12) had events between BAV and NCS including 3 deaths, and 7.5% (n=7) had events after NCS including 2 deaths. In IPTW propensity analyses, the incidence of the primary outcome (20.4% vs 20.0%; OR 0.93, 95% CI: 0.38-2.29) and three-month survival (89.2% vs 90.0%; IPTW-adjusted HR 0.90, 95% CI: 0.31-2.60) were similar in both groups., Conclusions: Patients with SAS managed conservatively before urgent NCS are at high risk of events. A systematic invasive strategy using BAV does not provide a significant improvement in clinical outcome.

Background: Transfemoral percutaneous transcatheter aortic valve implantation (TF-TAVI) is a safe, reproducible and established procedure, mainly performed under local anaesthesia, which is mostly administered and monitored by a dedicated anaesthesia team (regular approach). Our centre has developed a standardized pathway of care, and eligible patients are selected for a minimalist TF-TAVI, entirely managed by operators without the presence of the anaesthesia team in the operating room, like most interventional coronary procedures ("percutaneous coronary intervention-like" approach [PCI approach])., Aim: To compare the safety and efficacy of TF-TAVI performed with the PCI approach versus the regular approach., Methods: The analysis population comprised all patients who underwent TF-TAVI with the PCI or regular approach in our institution from November 2016 to July 2019. The two co-primary endpoints were early safety composite and early efficacy composite at 30days as defined by the Valve Academic Research Consortium-2. The PCI (n=137) and Regular (n=221) approaches were compared using the propensity score based method of inverse probability of treatment weighting., Results: No differences were observed after comparison of TAVI performed with the PCI or regular approach regarding the composite safety endpoint (7.3% vs. 11.3%; odds ratio 0.63, 95% confidence interval 0.37 to 1.07; P=0.086) or the composite efficacy endpoint (4.4% vs. 6.3%; odds ratio 0.78, 95% confidence interval 0.41 to 1.49; P=0.45)., Conclusions: This study suggests that the efficacy and safety of TF-TAVI entirely managed by a PCI approach for selected patients are not different to those when TF-TAVI is performed with the attendance of a full anaesthesia care team. The PCI approach appears to be a safe and efficient clinical pathway, providing an appropriate and rational utilization of anaesthesiology resources, and could be used for the majority of TF-TAVI procedures., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: Systems of care have been challenged to control progression of the COVID-19 pandemic. Whether this has been associated with delayed reperfusion and worse outcomes in French patients with ST-segment elevation myocardial infarction (STEMI) is unknown., Aim: To compare the rate of STEMI admissions, treatment delays, and outcomes between the first peak of the COVID-19 pandemic in France and the equivalent period in 2019., Methods: In this nationwide French survey, data from consecutive STEMI patients from 65 centres referred for urgent revascularization between 1 March and 31 May 2020, and between 1 March and 31 May 2019, were analysed. The primary outcome was a composite of in-hospital death or non-fatal mechanical complications of acute myocardial infarction., Results: A total of 6306 patients were included. During the pandemic peak, a 13.9±6.6% (P=0.003) decrease in STEMI admissions per week was observed. Delays between symptom onset and percutaneous coronary intervention were longer in 2020 versus 2019 (270 [interquartile range 150-705] vs 245 [140-646]min; P=0.013), driven by the increase in time from symptom onset to first medical contact (121 [60-360] vs 150 [62-420]min; P=0.002). During 2020, a greater number of mechanical complications was observed (0.9% vs 1.7%; P=0.029) leading to a significant difference in the primary outcome (112 patients [5.6%] in 2019 vs 129 [7.6%] in 2020; P=0.018). No significant difference was observed in rates of orotracheal intubation, in-hospital cardiac arrest, ventricular arrhythmias and cardiogenic shock., Conclusions: During the first peak of the COVID-19 pandemic in France, there was a decrease in STEMI admissions, associated with longer ischaemic time, exclusively driven by an increase in patient-related delays and an increase in mechanical complications. These findings suggest the need to encourage the population to seek medical help in case of symptoms., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

After 15 years of successive randomized, controlled trials, indications for transcatheter aortic valve replacement (TAVR) are rapidly expanding. In the coming years, this procedure could become the first line treatment for patients with a symptomatic severe aortic stenosis and a tricuspid aortic valve anatomy. However, randomized, controlled trials have excluded bicuspid aortic valve (BAV), which is the most frequent congenital heart disease occurring in 1% to 2% of the total population and representing at least 25% of patients 80 years of age or older referred for aortic valve replacement. The use of a less invasive transcatheter therapy in this elderly population became rapidly attractive, and approximately 10% of patients currently undergoing TAVR have a BAV. The U.S. Food and Drug Administration and the "European Conformity" have approved TAVR for low-risk patients regardless of the aortic valve anatomy whereas international guidelines recommend surgical replacement in BAV populations. Given this progressive expansion of TAVR toward younger and lower-risk patients, heart teams are encountering BAV patients more frequently, while the ability of this therapy to treat such a challenging anatomy remains uncertain. This review will address the singularity of BAV anatomy and associated technical challenges for the TAVR procedure. We will examine and summarize available clinical evidence and highlight critical knowledge gaps regarding TAVR utilization in BAV patients. We will provide a comprehensive overview of the role of computed tomography scans in the diagnosis, and classification of BAV and TAVR procedure planning. Overall, we will offer an integrated framework for understanding the current role of TAVR in the treatment of bicuspid aortic stenosis and for guiding physicians in clinical decision-making.

Background: A reduction of admission for MI has been reported in most countries affected by COVID-19. No clear explanation has been provided., Methods: To report the incidence of myocardial infarction (MI) admission during COVID-19 pandemic and in particular during national lockdown in two unequally affected French provinces (10-million inhabitants) with a different media strategy, and to describe the magnitude of MI incidence changes relative to the incidence of COVID-19-related deaths. A longitudinal study to collect all MIs from January 1 until May 17, 2020 (study period) and from the identical time period in 2019 (control period) was conducted in all centers with PCI-facilities in northern "Hauts-de-France" province and western "Pays-de-la-Loire" Province. The incidence of COVID-19 fatalities was also collected., Findings: In "Hauts-de-France", during lockdown (March 18-May 10), 1500 COVID-19-related deaths were observed. A 23% decrease in MI-IR (IRR=0.77;95%CI:0.71-0.84, p <0.001) was observed for a loss of 272 MIs (95%CI:-363,-181), representing 18% of COVID-19-related deaths. In "Pays-de-la-Loire", 382 COVID-19-related deaths were observed. A 19% decrease in MI-IR (IRR=0.81; 95%CI=0.73-0.90, p <0.001) was observed for a loss of 138 MIs (95%CI:-210,-66), representing 36% of COVID-19-related deaths. While in "Hauts-de-France" the MI decline started before lockdown and recovered 3 weeks before its end, in "Pays-de-la-Loire", it started after lockdown and recovered only by its end. In-hospital mortality of MI patients was increased during lockdown in both provinces (5.0% vs 3.4%, p =0.02)., Interpretation: It highlights one of the potential collateral damages of COVID-19 outbreak on cardiovascular health with a dramatic reduction of MI incidence. It advocates for a careful and weighted communication strategy in pandemic crises., Funding: The study was conducted without external funding., Competing Interests: Dr. Lemesle reports personal fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Lilly, MSD, Mylan, Novartis, Novonordisk, Pfizer, Sanofi Aventis, Servier, outside the submitted work. Dr Delhaye reports personal fees from Medtronic outside the submitted work. Dr. Cayla reports personal fees from Amgen, personal fees from Astra Zeneca, personal fees from Bayer, personal fees from Biotronik, personal fees from Bristol Myers Squibb, grants and personal fees from Medtronic, personal fees from MSD, personal fees from Pfizer, personal fees from Sanofi, outside the submitted work. The other authors do not report any conflict of interest., (© 2021 The Authors.)

Objective: The study's aim was to analyze the capacity of human valve interstitial cells (VICs) to participate in aortic valve angiogenesis. Approach and Results: VICs were isolated from human aortic valves obtained after surgery for calcific aortic valve disease and from normal aortic valves unsuitable for grafting (control VICs). We examined VIC in vitro and in vivo potential to differentiate in endothelial and perivascular lineages. VIC paracrine effect was also examined on human endothelial colony-forming cells. A pathological VIC (VIC p ) mesenchymal-like phenotype was confirmed by CD90 + /CD73 + /CD44 + expression and multipotent-like differentiation ability. When VIC p were cocultured with endothelial colony-forming cells, they formed microvessels by differentiating into perivascular cells both in vivo and in vitro. VIC p and control VIC conditioned media were compared using serial ELISA regarding quantification of endothelial and angiogenic factors. Higher expression of VEGF (vascular endothelial growth factor)-A was observed at the protein level in VIC p -conditioned media and confirmed at the mRNA level in VIC p compared with control VIC. Conditioned media from VIC p induced in vitro a significant increase in endothelial colony-forming cell proliferation, migration, and sprouting compared with conditioned media from control VIC. These effects were inhibited by blocking VEGF-A with blocking antibody or siRNA approach, confirming VIC p involvement in angiogenesis by a VEGF-A dependent mechanism., Conclusions: We provide here the first proof of an angiogenic potential of human VICs isolated from patients with calcific aortic valve disease. These results point to a novel function of VIC p in valve vascularization during calcific aortic valve disease, with a perivascular differentiation ability and a VEGF-A paracrine effect. Targeting perivascular differentiation and VEGF-A to slow calcific aortic valve disease progression warrants further investigation.

Background Ultrasound (US) guidance provides the unique opportunity to control the puncture zone of the artery during transfemoral transcatheter aortic valve replacement and may decrease major vascular complications (VC) and life-threatening or major bleeding complications. This study aimed to evaluate the clinical impact of US guidance using a propensity score-matched comparison. Methods and Results US guidance was implemented as the default approach for all transfemoral transcatheter aortic valve replacement cases in our institution in June 2013. We defined 3 groups of consecutive patients according to the method of puncture (fluoroscopic/US guidance) and the use of a transcatheter heart valve. Patients in the US-guided second-generation group (Sapien XT [Edwards Lifesciences, Irvine, CA], Corevalve [Medtronic, Dublin, Ireland]) were successfully 1:1 matched with patients in the fluoroscope-guided second-generation group (n=95) with propensity score matching. In a second analysis we described the consecutive patients of the US-guided third-generation group (Evolut-R [Medtronic], Sapien 3 [Edwards Lifesciences], n=308). All vascular and bleeding complications were reduced in the US-guided second-generation group compared with the fluoroscope-guided second-generation group: VC (16.8% versus 6.3%; P =0.023); life-threatening or major bleeding (22.1% versus 6%; P =0.004); and VC related to vascular access (12.6% versus 4.2%; P =0.052). In the US-guided third-generation group the rates of major VC and life-threatening or major bleeding were 3.2% (95% CI, 1.6% to 5.9%) and 3.6% (95% CI, 1.8% to 6.3%). In the overall population (n=546), life-threatening or major bleeding was associated with a 1.7-fold increased mortality risk ( P =0.02). Conclusions We demonstrated that US guidance effectively reduced VC and bleeding complications for transfemoral transcatheter aortic valve replacement and should be considered the standard puncture method. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02628509.