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Atherosclerotic cardiovascular disease (ASCVD) and consequent acute coronary syndromes (ACS) are substantial contributors to morbidity and mortality across Europe. Fortunately, as much as two thirds of this disease's burden is modifiable, in particular by lipid-lowering therapy (LLT). Current guidelines are based on the sound premise that, with respect to low-density lipoprotein cholesterol (LDL-C), "lower is better for longer", and recent data have strongly emphasised the need for also "the earlier the better". In addition to statins, which have been available for several decades, ezetimibe, bempedoic acid (also as fixed dose combinations), and modulators of proprotein convertase subtilisin/kexin type 9 (PCSK9 inhibitors and inclisiran) are additionally very effective approaches to LLT, especially for those at very high and extremely high cardiovascular risk. In real life, however, clinical practice goals are still not met in a substantial proportion of patients (even in 70%). However, with the options we have available, we should render lipid disorders a rare disease. In April 2021, the International Lipid Expert Panel (ILEP) published its first position paper on the optimal use of LLT in post-ACS patients, which complemented the existing guidelines on the management of lipids in patients following ACS, which defined a group of "extremely high-risk" individuals and outlined scenarios where upfront combination therapy should be considered to improve access and adherence to LLT and, consequently, the therapy's effectiveness. These updated recommendations build on the previous work, considering developments in the evidential underpinning of combination LLT, ongoing education on the role of lipid disorder therapy, and changes in the availability of lipid-lowering drugs. Our aim is to provide a guide to address this unmet clinical need, to provide clear practical advice, whilst acknowledging the need for patient-centred care, and accounting for often large differences in the availability of LLTs between countries., Competing Interests: Declarations. Funding: No external funding was used in the preparation of this article. Conflict of interest: Dr. Banach has received research grant(s)/support from Amgen, Daiichi-Sankyo, Mylan/Viatris, and Sanofi, and has received honoraria and/or served as a consultant for Adamed, Amgen, Daiichi-Sankyo, Esperion, Kogen, KRKA, Lilly, MSD, Mylan/Viatris, NewAmsterdam Pharma, Novartis, Novo Nordisk, Polfarmex, Polpharma, Sanofi-Regeneron, Servier, Teva, and Zentiva. Dr. Reiner has received honoraria from Sanofi and Novartis. Dr. Cicero has received personal fees from Mylan-Viatris, Sharper, and Servier. Dr. Dyrbuś has received fee for scientific activities from Novartis, Sanofi-Aventis, and Amgen. Dr. Fedacko has received a consultancy fee from Sanofi, Amgen and Novo Nordisk, and a research grant from Pfizer. Dr. Fras has received grants and fees for scientific activities from Amgen, Krka, Novartis, Swix BioPharma, and Viatris. Dr. Gaita has received honoraria from Amgen, AstraZeneca, Bayer, Berlin Chemie, Biofarm, Boehringer Ingelheim, Galenica, GSK, Gedeon Richter, Krka, MSD, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier, Terapia, Vifor Pharma, and Zentiva. Dr. Gierlotka reports honoraria from Sanofi, Novartis, Bayer, Amgen, Novo Nordisk, AstraZeneca, Servier. Dr. Gouni-Berthold has served as consultant and received honoraria from Akcea, Amgen, Daiichi-Sankyo, Novartis, Sanofi-Regeneron, Ultragenyx, and Amarin. Dr. Jankowski has received a research grant from Sanofi and has served as a consultant for Novartis, Servier, and Zentiva. Dr. Járai has served as a consultant for and received honoraria from Bayer, Berlin-Chemie, Boehringer Ingelheim, Egis, MSD, Novartis (Sandoz), Novo Nordisk, Pfizer, Richter Gedeon, Sanofi, Servier, and Teva. Dr. Latkovskis has given talks, attended conferences, received consultancy fees, and/or participated in trials sponsored by Abbott Laboratories, Amgen, AstraZeneca, Berlin-Chemie/Menarini, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Grindex, KRKA, MSD, Mylan, Novartis, Novo Nordisk, Pfizer, Sanofi, Servier Laboratories, Siemens Laboratories, and Zentiva. Dr. Magda has received consultation fees from Novartis, Sanofi, and Servier. Dr. Margetic has received a fee for scientific activities from Novartis and Sanofi. Dr. Ostadal has received honoraria from Getinge, Abiomed, Edwards, Fresenius/Xenios, AstraZeneca, Bayer, Boehringer Ingelheim, Amgen, Sanofi, Servier, Novartis, Pfizer, AOP, and GSK. Dr Paragh has received lectures fees from Hungarian branches of Novartis, Richter Gedeon, and Sandoz. Dr. Paneni has received honoraria from Novo Nordisk. Dr. Pećin has received grants and fees for scientific activities from Amgen, Bayer, Novartis, and Sanofi. Dr. Pella has received grant support and honoraria from Sanofi, Amgen, MSD, Servier, Novartis, and Pfizer. Dr. Postadzhiyan reports fees for educational activities from Amgen, AstraZeneca, KRKA, Novartis, Servier, Teva, and Zentiva. Dr. Stoian has given lectures, received honoraria and research support, and participated in conferences, advisory boards, and clinical trials sponsored by pharmaceutical companies, from AstraZeneca, Amgen, Boehringer Ingelheim, Coca-Cola, Eli Lilly, Merck, Medtronic, MSD, Medochemie, Novo Nordisk, Novartis, Roche Diagnostics, Servier, Sandoz, and Sanofi. Dr. Trbusic has received a fee for scientific activities from Novartis and Sanofi. Dr. Udroiu has received a fee for scientific activities from AstraZeneca and Pfizer. Dr. Viigimaa reports fees for educational activities from Amgen, AstraZeneca, Novartis, Novo Nordisk, Menarini, Servier, and Swixx BioPharma. Dr. Vinereanu has received research grants and expert fees from Amgen, Sanofi, Novartis, and Servier. Dr. Vlachopoulos has received grants and fees for scientific activities from Amgen, Sanofi, and MSD. Dr. Vrablik has received personal fees from Abbott, Amgen, AstraZeneca, BMS, Genzyme, KRKA, MSD Idea, Novartis, Pfizer, and Sanofi-Regeneron. Dr. Vulic has received a fee for scientific activities from Sanofi. Dr. Penson owns four shares in AstraZeneca PLC and has received honoraria from Amgen and Sanofi and travel/accommodation reimbursement for events sponsored by AKCEA, Amgen, AMRYT, Link Medical, Mylan, and Napp. All other authors declare that they have no potential conflicts of interest that might be relevant to the contents of this article. Authors’ contributions: Dr. Banach: Conceptualisation; data curation; methodology; project administration; supervision; validation; visualisation; writing, reviewing, and editing; revisions; preparing the final version of the paper. Dr. Penson: Data curation; investigation; methodology; validation; visualisation; first draft preparation; reviewing and editing. Dr Surma: data curation, visualisation, draft figures preparations; reviewing and editing. Drs. Reiner, Bajraktari, Bielecka-Dabrowa, Bunc, Bytyçi, Ceska, Cicero, Dudek, Dyrbuś, Fedacko, Fras, Gaita, Gavish, Gierlotka, Gil, Gouni-Berthold, Jankowski, Járai, Jóźwiak, Katsiki, Latkovskis, Magda, Margetic, Margoczy, Mitchenko, Durak-Nalbantic, Ostadal, Paragh, Petrulioniene, Paneni, Pećin, Pella, Postadzhiyan, Stoian, Trbusic, Udroiu, Viigimaa, Vinereanu, Vlachopoulos, Vrablik, and Vulic: Investigation, methodology; validation; writing, reviewing, and editing; final revisions and approval. Data availability statement: Data sharing is not applicable to this article as no datasets were generated for this article. Ethics approval: Not applicable. Code availability: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable., (© 2024. The Author(s).)

Background: There are limited head-to-head randomised trials comparing the performance of different transcatheter heart valves (THVs)., Aims: We aimed to evaluate the non-inferiority of the balloon-expandable Myval THV series compared to the balloon-expandable SAPIEN THV series or the self-expanding Evolut THV series., Methods: The LANDMARK trial randomised 768 patients in a 1:1 ratio, (Myval THV series [n=384] vs contemporary series with 50% SAPIEN THV series [n=192] and 50% Evolut THV series [n=192]). The non-inferiority of Myval over the SAPIEN or Evolut THV series in terms of the 30-day primary composite safety and effectiveness endpoint as per the third Valve Academic Research Consortium (VARC-3) was tested in an intention-to-treat population with a predefined statistical power of 80% (1-sided alpha of 5%) for a non-inferiority margin of 10.44%., Results: The Myval THV series achieved non-inferiority for the primary composite endpoint over the SAPIEN THV series (24.7% vs 24.1%, risk difference [95% confidence interval {CI}]: 0.6% [not applicable {NA} to 8.0]; p=0.0033) and the Evolut THV series (24.7% vs 30.0%, risk difference [95% CI]: -5.3% [NA to 2.5]; p<0.0001). The incidences of pacemaker implantation were comparable (Myval THV series: 15.0%, SAPIEN THV series: 17.3%, Evolut THV series: 16.8%). At 30 days, the mean pressure gradient and effective orifice area were significantly better with the Myval THV series compared to the SAPIEN THV series (p<0.0001) and better with the Evolut THV series than with the Myval THV series (p<0.0001). At 30 days, the proportion of moderate to severe prosthetic valve regurgitation was numerically higher with the Evolut THV series compared to the Myval THV series (7.4% vs 3.4%; p=0.06), while not significantly different between the Myval THV series and the SAPIEN THV series (3.4% vs 1.6%; p=0.32)., Conclusions: The Myval THV series is non-inferior to the SAPIEN THV series and the Evolut THV series in terms of the primary composite endpoint at 30 days., Clinical Trial Registration: ClinicalTrials.gov: NCT04275726; EudraCT number 2020-000,137-40.

Background: Prosthesis-patient mismatch after transcatheter aortic valve replacement (TAVR) can be measured echocardiographically (measured prosthesis-patient mismatch [PPMm]) or predicted (predicted prosthesis-patient mismatch [PPMp]) using published effective orifice area (EOA) reference values. However, the clinical implications of PPM post-TAVR remain unclear., Objectives: This study aimed to elucidate the prevalence of PPMm and PPMp post-TAVR and their impact on mortality in a large international cohort., Methods: The IMPPACT TAVR (Impact of Measured or Predicted Prosthesis-pAtient mismatCh after TAVR) registry included 38,808 TAVR patients from 26 international centers. Valve Academic Research Consortium 3 criteria were used to define prosthesis-patient mismatch severity. EOA was determined echocardiographically (PPMm) or predicted (PPMp) based on core lab-derived EOA reference values. The primary endpoint was 2-year all-cause mortality., Results: The prevalence of PPMp (moderate: 6.8%, severe: 0.6%) was significantly lower than that of PPMm (moderate: 20.7%, severe: 4.3%; P < 0.001) with negligible correlation between the 2 methods (Kendall's tau c correlation coefficient: 0.063; P < 0.001). In unadjusted analyses, severe PPMm adversely influenced 2-year survival (HR: 1.22; 95% CI: 1.02-1.45; P = 0.027), whereas severe PPMp was not associated with outcomes (HR: 0.81; 95% CI: 0.55-1.19; P = 0.291). After adjusting for confounders, neither PPMm nor PPMp had a significant effect on 2-year all-cause mortality., Conclusions: PPMm and PPMp were associated with different patient characteristics, with PPMm tending toward worse (especially low flow) and PPMp toward better (especially women) survival. After adjusting for confounders, neither PPMm nor PPMp significantly affected 2-year all-cause mortality. Hence, valve selection should not solely be based on hemodynamics but rather on a holistic approach, including patient and procedural specifics., Competing Interests: Funding Support and Author Disclosures This work was supported by the Deutsche Forschungsgemeinschaft (397484323) to Drs Guthoff, Matti Adam and Stephan Baldus, and Mauri; PA 2409/5-2 to Drs Thurow and Pauly; the Dean’s Office, Faculty of Medicine, University of Cologne (clinician scientist position) to Dr Guthoff; and the Center for Molecular Medicine Cologne (Baldus B-02) to Dr Stephan Baldus. Dr Abdel-Wahab’s institution has received speaker honoraria and/or consultancy fees from Abbott, Boston Scientific, and Medtronic. Dr Kim has received proctor and personal fees from Abbott, Boston Scientific, Meril Life Sciences, and Shockwave Med; is a member of the advisory boards for Abbott, Boston Scientific, and HID Imaging; and Dr Kim’s institution has received fees from Boston Scientific. Dr Nombela-Franco has served as proctor for Abbott and Edwards Lifesciences. Dr Matjaz Bunc served as proctor for TAVR procedures with Edwards Lifesciences, Medtronic, Meril, and Abbott. Matjaz Bunc is a member of the advisory boards for Medtronic and Edwards Lifesciences. Dr Veulemans has received speaker and/or study honoraria from Edwards Lifesciences, Medtronic, and Boston Scientific. Dr Tanja Rudolph has received lecture fees from Abbott, SIS Medical and Translumina. Dr Zeus has received speaker and/or study honoraria from Edwards Lifesciences, Medtronic, and Boston Scientific. 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: Transcatheter aortic valve implantation is an established, guideline-endorsed treatment for severe aortic stenosis. Precise sizing of the balloon-expandable Myval transcatheter heart valve (THV) series with the aortic annulus is facilitated by increasing its diameter in 1·5 mm increments, compared with the usual 3 mm increments in valve size. The LANDMARK trial aimed to show non-inferiority of the Myval THV series compared with the contemporary THVs Sapien Series (Edwards Lifesciences, Irvine, CA, USA) or Evolut Series (Medtronic, Minneapolis, MN, USA)., Methods: In this prospective, multinational, randomised, open-label, non-inferiority trial across 31 hospitals in 16 countries (Germany, France, Sweden, the Netherlands, Italy, Spain, New Zealand, Portugal, Greece, Hungary, Poland, Slovakia, Slovenia, Croatia, Estonia, and Brazil), 768 participants with severe symptomatic native aortic stenosis were randomly assigned (1:1) to the Myval THV or a contemporary THV. Eligibility was primarily decided by the heart team in accordance with 2021 European Society of Cardiology guidelines. As per the criteria of the third Valve Academic Research Consortium, the primary endpoint at 30 days was a composite of all-cause mortality, all stroke, bleeding (types 3 and 4), acute kidney injury (stages 2-4), major vascular complications, moderate or severe prosthetic valve regurgitation, and conduction system disturbances resulting in a permanent pacemaker implantation. Non-inferiority of the study device was tested in the intention-to-treat population using a non-inferiority margin of 10·44% and assuming an event rate of 26·10%. This trial is registered with ClinicalTrials.gov, NCT04275726, and EudraCT, 2020-000137-40, and is closed to new participants., Findings: Between Jan 6, 2021, and Dec 5, 2023, 768 participants with severe symptomatic native aortic stenosis were randomly assigned, 384 to the Myval THV and 384 to a contemporary THV. 369 (48%) participants had their sex recorded as female, and 399 (52%) as male. The mean age of participants was 80·0 years (SD 5·7) for those treated with the Myval THV and 80·4 years (5·4) for those treated with a contemporary THV. Median Society of Thoracic Surgeons scores were the same in both groups (Myval 2·6% [IQR 1·7-4·0] vs contemporary 2·6% [1·7-4·0]). The primary endpoint showed non-inferiority of the Myval (25%) compared with contemporary THV (27%), with a risk difference of -2·3% (one-sided upper 95% CI 3·8, p non-inferiority <0·0001). No significant difference was seen in individual components of the primary composite endpoint., Interpretation: In individuals with severe symptomatic native aortic stenosis, the Myval THV met its primary endpoint at 30 days., Funding: Meril Life Sciences., Competing Interests: Declaration of interests NvR reports grant funding and personal fees from Abbott; grants from Philips, Biotronik, and Medtronic; and personal fees from MicroPort, Bayer, and RainMed Medical outside the submitted work. IJA-S reports being a proctor for Medtronic, Boston Scientific, and Meril Life Sciences. AIj reports consulting fees from Meril Life Sciences, Medtronic, Angiocare, Keystone Heart, PulseCath, Salveo, Abbott, Philips, Fysicon, Cardiawave, Pi Medical, and Svelte. DU reports lecture and educational event fees from Medtronic; a lecture fee from and being a proctor for Meril Life Sciences; and being a member of the Medtronic EMEA surgical advisory board. RSH reports grant funding from Bayer; and speaker fees from Amgen, Novartis, and Abbott outside the submitted work. MW reports institutional research funding from Emboline, Meril Life Sciences, Edwards Lifesciences, and TransAortic Medical. MPa reports honoraria from Boston Scientific, Philips, and Abbott. OA reports research grants and lecture fees from and being a proctor for Abbott; and advisory board participation for and support for attending meetings from Meril Life Sciences. W-KK reports honoraria or consultancy fees from Abbott, Boston Scientific, Edwards Lifesciences, Meril Life Sciences, and Hi-D Imaging; and participation on an advisory board or data and safety monitoring board for Abbott and Boston Scientific. JR reports being a consultant with Medtronic and Qatma; being a proctor for Medtronic; and travel support for attending meetings from Meril Life Sciences, Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific. AT reports a grant from the Fukuda Foundation for Medical Technology. SG reports honoraria or consultancy fees from Biosensors. PWS reports consultancy fees from SMT, Novartis, Meril Life Sciences, Xeltis, and Philips. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background/Objectives : To date, data regarding the characteristics and management of obstructive, stable coronary artery disease (CAD) encountered in patients undergoing transcatheter aortic valve implantation (TAVI) are sparse. The aim of the study was to analyze granular details, treatment, and outcomes of patients undergoing TAVI with obstructive, stable CAD from real-world practice. Methods : REVASC-TAVI (Management of myocardial REVASCularization in patients undergoing Transcatheter Aortic Valve Implantation with coronary artery disease) is an investigator-initiated, multicenter registry, which collected data from patients undergoing TAVI with obstructive stable CAD found during the pre-TAVI work-up. Results : A total of 2025 patients from 30 centers worldwide with complete follow-up were included in the registry. Most patients had single-vessel CAD (56.1%). An involvement of proximal coronary tracts was detected in 62.5% of cases, with 12.0% of patients having CAD in left main (LM). Most patients received percutaneous coronary intervention (PCI) (n = 1617, 79.9%), especially those with proximal CAD (90.4%). At 2 years, the rates of all-cause death [Kaplan-Meier (KM) estimates 20.1% vs. 18.8%, p log-rank = 0.86] and of the composite of all-cause death, stroke, myocardial infarction, and rehospitalization for heart failure (KM estimates 29.7% vs. 27.5%, p log-rank = 0.82) did not differ between patients undergoing PCI and those who were not. Conclusions : Patients undergoing TAVI with obstructive CAD more commonly had a single-vessel disease and an involvement of proximal coronary tracts. They were commonly treated with PCI, with similar outcomes compared to those treated conservatively., Competing Interests: Thomas Pilgrim received research grants to the institution from Biotronik, Boston Scientific, and Edwards Lifesciences; and speaker/consultancy fees from Medtronic, Boston Scientific, Biotronik, and HighLifeSAS. Ole De Backer received institutional research grants and/or consulting fees from Abbott and Boston Scientific. Lars Sondergaard received consultant fees and/or institutional research grants from Abbott, Boston Scientific, Medtronic, and SMT. Maurizio Taramasso is a consultant for Abbott, Edwards Lifesciences, Boston Scientific, Shenqi Medical, CoreMedic, MEDIRA, 4tech, Simulands, Occlufit, and MTEX. Corrado Tamburino is a consultant for Medtronic. All other authors have nothing to disclose.

The early unfractionated heparin (UFH) treatment in patients with ST-elevation myocardial infarction (STEMI) is a single-center, open-label, randomized controlled trial. The study population are patients with STEMI that undergo primary percutaneous coronary intervention (PPCI). The trial was designed to investigate whether early administration of unfractionated heparin immediately after diagnosis of STEMI is beneficial in terms of patency of infarct-related coronary artery (IRA) when compared to established UFH administration at the time of coronary intervention. The patients will be randomized in 1:1 fashion in one of the two groups. The primary efficacy endpoint of the study is Thrombolysis in myocardial infarction (TIMI) flow grades 2 and 3 on diagnostic coronary angiography. Secondary outcome measures are: TIMI flow after PPCI, progression to cardiogenic shock, 30-day mortality, ST-segment resolution, highest Troponin I and Troponin I values at 24 hours. The safety outcome is bleeding complications. The study of early heparin administration in patients with STEMI will address whether pretreatment with UFH can increase the rate of spontaneous reperfusion of infarct-related coronary artery., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Fister et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Data on the likelihood of left ventricle (LV) recovery in patients with severe LV dysfunction and severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and its prognostic value are limited., Aims: We aimed to assess the likelihood of LV recovery following TAVI, examine its association with midterm mortality, and identify independent predictors of LV function., Methods: In our multicentre registry of 17 TAVI centres in Western Europe and Israel, patients were stratified by baseline LV function (ejection fraction [EF] >/≤30%) and LV response: no LV recovery, LV recovery (EF increase ≥10%), and LV normalisation (EF ≥50% post-TAVI)., Results: Our analysis included 10,872 patients; baseline EF was ≤30% in 914 (8.4%) patients and >30% in 9,958 (91.6%) patients. The LV recovered in 544 (59.5%) patients, including 244 (26.7%) patients whose LV function normalised completely (EF >50%). Three-year mortality for patients without severe LV dysfunction at baseline was 29.4%. Compared to this, no LV recovery was associated with a significant increase in mortality (adjusted hazard ratio 1.32; p<0.001). Patients with similar LV function post-TAVI had similar rates of 3-year mortality, regardless of their baseline LV function. Three variables were associated with a higher likelihood of LV recovery following TAVI: no previous myocardial infarction (MI), estimated glomerular filtration rate >60 mL/min, and mean aortic valve gradient (mAVG) (expressed either as a continuous variable or as a binary variable using the standard low-flow, low-gradient aortic stenosis [AS] definition)., Conclusions: LV recovery following TAVI and the extent of this recovery are major determinants of midterm mortality in patients with severe AS and severe LV dysfunction undergoing TAVI. Patients with no previous MI and those with an mAVG >40 mmHg show the best results following TAVI, which are at least equivalent to those for patients without severe LV dysfunction. (ClinicalTrials.gov: NCT04031274).

Background: The COVID-19 pandemic adversely affected health care systems. Patients in need of transcatheter aortic valve replacement (TAVR) are especially susceptible to treatment delays., Objectives: This study sought to evaluate the impact of the COVID-19 pandemic on global TAVR activity., Methods: This international registry reported monthly TAVR case volume in participating institutions prior to and during the COVID-19 pandemic (January 2018 to December 2021). Hospital-level information on public vs private, urban vs rural, and TAVR volume was collected, as was country-level information on socioeconomic status, COVID-19 incidence, and governmental public health responses., Results: We included 130 centers from 61 countries, including 65,980 TAVR procedures. The first and second pandemic waves were associated with a significant reduction of 15% (P < 0.001) and 7% (P < 0.001) in monthly TAVR case volume, respectively, compared with the prepandemic period. The third pandemic wave was not associated with reduced TAVR activity. A greater reduction in TAVR activity was observed in Africa (-52%; P = 0.001), Central-South America (-33%; P < 0.001), and Asia (-29%; P < 0.001). Private hospitals (P = 0.005), urban areas (P = 0.011), low-volume centers (P = 0.002), countries with lower development (P < 0.001) and economic status (P < 0.001), higher COVID-19 incidence (P < 0.001), and more stringent public health restrictions (P < 0.001) experienced a greater reduction in TAVR activity., Conclusions: TAVR procedural volume declined substantially during the first and second waves of the COVID-19 pandemic, especially in Africa, Central-South America, and Asia. National socioeconomic status, COVID-19 incidence, and public health responses were associated with treatment delays. This information should inform public health policy in case of future global health crises., Competing Interests: Funding Support and Author Disclosures Dr Lefèvre has served as a proctor for Edwards Lifesciences; and received minor fees from Boston Scientific, Terumo, and Abbott. Dr Pilgrim has received research, travel, or educational grants to the institution without personal remuneration from Biotronik, Boston Scientific, Edwards Lifesciences, and ATSens; and speaker fees and consultancy fees to the institution from Biotronik, Boston Scientific, Edwards Lifesciences, Abbott, Medtronic, Biosensors, and Highlife. Dr Van Mieghem has received research grant support from Abbott Vascular, Boston Scientific, Edwards Lifesciences, Medtronic, Daiichi Sankyo, AstraZeneca, Teleflex; and advisory board fees from Abbott Vascular, Boston Scientific, Inari, JenaValve, Medtronic, Daiichi Sankyo, AstraZeneca, Siemens, Pie Medical, and Teleflex. Dr Swaans has served as a proctor/lecturer for Abbott Vascular, Boston Scientific, Bioventrix Inc, Cardiac Dimensions, Edwards Lifesciences, GE Healthcare, Medtronic, and Philips Healthcare. Dr Prendergast has received speaker/consultancy fees from Medtronic, MicroPort, Anteris, and Edwards Lifesciences. Dr Resar has received institutional research funding from Medtronic, Edwards Lifesciences, and Abbott; and served as a TAVR proctor for Medtronic. Dr Chen has served as a consultant for Venus MedTech. Dr Hildick-Smith has received research funds and speaker fees from Medtronic. Dr Spence has received TAVR proctoring and consultancy fees from Medtronic, Boston Scientific, and Edwards Lifesciences. Dr Bunc has served as a proctor for Abbott, Meril, Edwards Lifesciences, and Medtronic. Dr Molnár has served as a consultant for Medtronic and Abbott. Dr Toggweiler has served as a consultant and proctor for Medtronic, Boston Scientific, and Biosensors; has served as a proctor for Edwards Lifesciences and Abbott Vascular; has served as a consultant for Medira, Shockwave, Teleflex, atHeart Medical, Cardiac Dimensions, and Polares Medical; has received institutional research grants from Boston Scientific, Fumedica, and Novartis; has received speaker honoraria from Sanofi, AstraZeneca, ReCor Medical, and Daiichi Sankyo; and holds equity in Hi-D Imaging. Dr Ojeda has received consulting fees from Medtronic and Edwards Lifesciences; and speaker fees from Philips and Word Medica. Dr Toutouzas has served as a proctor for Medtronic, Abbott, Myval, and Boston Scientific. Dr AlMerri has served as a TAVR proctor for Medtronic. Dr Noble has served as a proctor for Medtronic; and received institutional grant support from Edwards Lifesciences, Boston Scientific, Abbott Vascular, and Medtronic. Dr Kala has served as a consultant for Boston Scientific; served on the Speakers Bureau for Edwards Lifesciences, Servier, and AstraZeneca; and received research support from Novartis. Dr Kurt has served as a TAVR proctor for Abbott. Dr Yin has served as a TAVR proctor for Medtronic, Edwards Lifesciences, and Abbott. Dr Sztejfman has served as a proctor for Boston Scientific, Edwards Lifesciences, Medtronic, Meril Life Sciences, and MicroPort. Dr Mendiz has served as a proctor for Medtronic, Boston Scientific, and Edwards Lifesciences. Dr Gunasekaran has received fees from Medtronic, Meril Life Sciences, Abbott, and Boston Scientific. Dr Kao has served as a proctor for Medtronic and Edwards Lifesciences. Dr Dager has served as a consultant for Medtronic. Dr Ferrero-Guadagnoli has served as a proctor for Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Modine has served as a consultant for and received honorarium from Abbott, Medtronic, and Edwards Lifesciences. Dr Hayashida has served as a proctor for Edwards Lifesciences, Medtronic, and Abbott. Dr Makkar has received research grants from Abbott, Edwards Lifesciences, and Boston Scientific, and served as a consultant for Cordis and Medtronic. Dr Mylotte has received institutional grant funding from Boston Scientific and Medtronic; and personal fees from Boston Scientific, Medtronic, and MicroPort. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Coronary lesions are supposed to be enclosed between proximal and distal reference segments (RSs), the sites with the largest lumens within the same vessel segment. Finding "healthy" landing zones has been fundamental for efficient stent implantation. Consequently, our study aimed to determine, using optical coherence tomography (OCT), to what degree RSs conform to this concept., Methods: Sixty-seven patients with a mean age of 63.5 years underwent culprit lesion stenting due to acute myocardial infarction (MI) (Group 1) or stable angina (Group 2). OCT was performed with commercially available equipment; all evaluations were made at RSs and minimal lumens., Results: Normal vessel wall was infrequent (~10%) at RSs. Acceptable external elastic 220°) occurred in 55% to 67% and in 28% to 31% of RSs, respectively. Tissue composition at RSs was similar in both study groups except for a greater accumulation of thin-cap fibroatheromas (TCFA) in acute MI (29% in Group 1 vs. 9% in Group 2, P=0.035). Flow deterioration after stenting was associated with TCFA clusters extending from culprit main bodies into proximal RSs (P=0.008)., Conclusions: Optimal landing zones for stent placement should frequently be searched for beyond the culprit lesion segments although utilizing the largest intrasegmental lumens does not seem to cause immediate harm. However, TCFA at the landings should definitely be avoided., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-924/coif). I.D.G. has received grants from Abbott Laboratories, Medtronic Laboratories, and Cryolife Inc. Payments have been provided to the institution in the form of grants and travel support for meetings; none are related to the creation of this manuscript. He is the Program Director for the Brano Heart Failure Forum and has received support related to travel. B.K. has received institutional grants from Saranas, Edwards LifeSciences, LLC, BioVentrix, Inc and Boston Scientific; none are related to the creation of this manuscript. The other authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: Treatment with a coronary sinus reducer (CSR) is a new therapeutic option for refractory angina patients. Preclinical studies have shown antiarrhythmic properties of coronary sinus narrowing. The possible antiarrhythmic effect of CSR implantation is unknown. This study aimed to determine the possible antiarrhythmic effects of CSR implantation as assessed by high-resolution electrocardiogram (hrECG) parameters., Methods: 24 patients from the Crossroad study randomized to either CSR treatment (n = 12) or a sham procedure (n = 12) had hrECG recorded at baseline and after 6 months. T-peak and T-end interval (TpTe) defined as the time difference between the peak amplitude of the T wave and the global end of the T wave, spatial angle between QRS complex and T axis defined as the angle between the ventricular depolarization and repolarization vectors using maximal (QRSTP) and mean (QRSTM) vector amplitudes and spatial ventricular gradient (SVG) calculated as integral of ECG voltages over the entire QRST complex were analyzed. Additionally, we analyzed parameters of QT and heart rate variability using time and frequency domain., Results: At baseline, all analyzed parameters were comparable between both groups and heart rate remained constant. The intragroup analysis did not show any significant change in TpTe, QRSTP, QRSTM, SVG, QT, and heart rate variability at follow-up. Furthermore, intergroup comparison between CSR implantation and sham procedure also did not show any significant difference in the change of analyzed parameters., Conclusions: Compared to the sham procedure, CSR implantation did not demonstrate a significant impact on the arrhythmogenic substrate assessed with hrECG., Clinical Trial Registration: Unique Identifier: NCT04121845, https://classic.clinicaltrials.gov/ct2/show/NCT04121845., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Background: The aim of this study was to compare short-term and mid-term outcomes in low-risk octogenarian population treated with transfemoral transcatheter aortic valve implantation (tf-TAVI) or minimally invasive aortic valve replacement (mini-AVR) for severe aortic stenosis., Methods: In this single-center, retrospective cohort study we gathered data on low-risk (Society of Thoracic Surgeons [STS] score < 4%) octogenarians before and after tf-TAVI and mini-AVR performed between January 2013 and May 2019; follow-up was completed in May 2022. Short-term outcomes were hospital length of stay, in-hospital all-cause mortality and other major postoperative outcomes. Mid-term clinical outcomes were 1‑year and 3‑year all-cause mortality. Propensity score-based matching was performed., Results: In total 106 patients were matched, resulting in 53 pairs. In-hospital complications were similar between the matched groups of patients with the exception of mild and moderate paravalvular leak (mini-AVR vs. tf-TAVI: mild PVL: 3.8% vs. 45.3%, p < 0.001; moderate PVL: 0% vs. 3.8%, p = 0.4952) and of postprocedural acute kidney injury that was more frequent in mini-AVR group (mini-AVR vs. tf-TAVI: 22.6% vs. 5.7%; p = 0.023). Hospital length of stay (p = 0.239) and in-hospital mortality (p = 0.495) did not differ between groups. The 1-year and 3‑year all-cause mortality Kaplan-Meier estimates were similar between mini-AVR and tf-TAVI., Conclusion: In the present study on low-risk octogenarians, transfemoral TAVI and minimally invasive AVR showed comparable short-term and mid-term results. Both procedures are deemed safe and effective. Larger RCTs will be required to determine which low-risk patients will benefit most from TAVI., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: The optimal timing to perform percutaneous coronary interventions (PCI) in transcatheter aortic valve implantation (TAVI) patients remains unknown., Aims: We sought to compare different PCI timing strategies in TAVI patients., Methods: The REVASC-TAVI registry is an international registry including patients undergoing TAVI with significant, stable coronary artery disease (CAD) at preprocedural workup. In this analysis, patients scheduled to undergo PCI before, after or concomitantly with TAVI were included. The main endpoints were all-cause death and a composite of all-cause death, stroke, myocardial infarction (MI) or rehospitalisation for congestive heart failure (CHF) at 2 years. Outcomes were adjusted using the inverse probability treatment weighting (IPTW) method., Results: A total of 1,603 patients were included. PCI was performed before, after or concomitantly with TAVI in 65.6% (n=1,052), 9.8% (n=157) or 24.6% (n=394), respectively. At 2 years, all-cause death was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (6.8% vs 20.1% vs 20.6%; p<0.001). Likewise, the composite endpoint was significantly lower in patients undergoing PCI after TAVI as compared with PCI before or concomitantly with TAVI (17.4% vs 30.4% vs 30.0%; p=0.003). Results were confirmed at landmark analyses considering events from 0 to 30 days and from 31 to 720 days., Conclusions: In patients with severe aortic stenosis and stable coronary artery disease scheduled for TAVI, performance of PCI after TAVI seems to be associated with improved 2-year clinical outcomes compared with other revascularisation timing strategies. These results need to be confirmed in randomised clinical trials.

Transcatheter aortic valve implantation (TAVI) improves event-free survival in patients with severe aortic stenosis, but patients' exercise capacity remains poor after the procedure. Therefore, we sought to compare the effects of a supervised center-based exercise training program and unsupervised exercise routine on exercise capacity and vascular function in patients after TAVI. Patients were randomized to either center-based exercise training (12-24 sessions of combined aerobic and low-weight resistance training twice weekly for 8-12 weeks) or an unsupervised home-based exercise routine (initial appraisal with detailed recommendations and monthly follow-up). Exercise capacity (cardiopulmonary testing) and vascular function (ultrasonographic measurement of flow-mediated vasodilation (FMD) and arterial stiffness) were assessed at the baseline and after the study period. We included 23 patients (mean age of 81 years, 61% women), with higher-than-expected drop-out rates (41%) because of the coronavirus-19 pandemic outbreak. Exercise capacity improved over time, irrespective of the intervention group: 0.09 mL/min/kg increase in peak oxygen uptake (95% CI [0.01-0.16]; p = 0.02), 8.2 Watts increase in workload (95% CI [0.6-15.8]; p = 0.034), and 47 s increase in cumulative exercise time (95% CI [5.0-89.6]; p = 0.029). A between-group difference in change over time (treatment effect) was detected only for FMD (4.49%; 95% CI [2.35; 6.63], p < 0.001), but not for other outcome variables. Both supervised and unsupervised exercise training improve exercise capacity and vascular function in patients after TAVI, with supervised exercise training possibly yielding larger improvements in vascular function, as determined by FMD.

Coronary sinus reducer (CSR) implantation is a new treatment option for patients with refractory angina pectoris. However, there is no evidence from a randomized trial that would show an improvement in exercise capacity after this treatment. The aim of this study was to evaluate the influence of CSR treatment on maximal oxygen consumption and compare it to a sham procedure. Twenty-five patients with refractory angina pectoris (Canadian Cardiovascular Society (CCS) class II-IV) were randomized to a CSR implantation ( n = 13) or a sham procedure ( n = 12). At baseline and after 6 months of follow-up, the patients underwent symptom-limited cardiopulmonary exercise testing with an adjusted ramp protocol and assessment of angina pectoris using the CCS scale and Seattle angina pectoris questionnaire (SAQ). In the CSR group, maximal oxygen consumption increased from 15.56 ± 4.05 to 18.4 ± 5.2 mL/kg/min ( p = 0.03) but did not change in the sham group ( p = 0.53); p for intergroup comparison was 0.03. In contrast, there was no difference in the improvement of the CCS class or SAQ domains. To conclude, in patients with refractory angina and optimized medical therapy, CSR implantation may improve oxygen consumption beyond that of optimal medical therapy.

Background: Degenerative aortic stenosis is an atherosclerotic-like process associated with impaired endothelial and autonomic function. Transcatheter aortic valve implantation (TAVI) has become a treatment of choice for patient with severe degenerative aortic stenosis at high surgical risk. The effect of this procedure on endothelial function measured with flow mediated dilatation (FMD) and autonomic function measured with heart rate variability (HRV) at different time-points of disease management (early and late follow-up) remains unknown., Methods: We prospectively included 50 patients with severe aortic stenosis who were deemed suitable for TAVI by the Heart Team. FMD and HRV parameters were collected at baseline ( < 24 h pre-TAVI), at early follow-up (up to 48 h post-TAVI) and at late follow-up (3-6 months post-TAVI)., Results: 43 patients (mean age 81 (75-85); 60% women) completed the study. FMD significantly improved from 2.8 ± 1.5% before TAVI to 4.7 ± 2.7% early after TAVI ( p < 0.001) and was later maintained on late follow-up (4.8 ± 2.7%, p = 0.936). Conversely, high-resolution ECG parameters remained preserved at early and improved at late follow-up after TAVI. Significant improvement was detected in a high frequency-domain parameter-HF (from 5231 ± 1783 to 6507 ± 1789 ms 2 ; p = 0.029) and in two Poincare plot parameters: ratio of the short- and long-term R-R variability in the Poincare plot-SD1/SD2 (from 0.682 to 0.884 ms 2 ; p = 0.003) and short-term R-R variability in the Poincare plot-SDRR (from 9.6 to 23.9 ms; p = 0.001). Echocardiographic parameters comprising baseline maximal aortic valve velocity (R = 0.415; p = 0.011), mean aortic gradient (R = 0.373; p = 0.018), indexed stroke volume (R = 0.503; p = 0.006), change in aortic valve maximal velocity (R = 0.365; p = 0.031), change in mean aortic gradient (R = 0.394; p = 0.019) and NT-proBNP (R = 0.491; p = 0.001) were found as significant predictors of change in FMD., Conclusions: Endothelial function measured with FMD and autonomic function obtained with HRV parameters significantly improve after TAVI. While endothelial function improves early and is maintained later after TAVI, autonomic function remains stable and improves on late follow-up. This is most likely caused by early hemodynamic changes after resolution of aortic valve obstruction and gradual left ventricular remodeling., Clinical Trial Registration: www.clinicaltrials.gov, identifier NCT04286893., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Aims: Paravalvular regurgitation (PVR) after transcatheter aortic valve implantation (TAVI) is associated with increased morbidity and mortality. The effect of transcatheter interventions to treat PVR after the index TAVI was investigated., Methods and Results: A registry of consecutive patients who underwent transcatheter intervention for ≥ moderate PVR after the index TAVI at 22 centers. The principal outcomes were residual aortic regurgitation (AR) and mortality at 1 year after PVR treatment. A total of 201 patients were identified: 87 (43%) underwent redo-TAVI, 79 (39%) plug closure, and 35 (18%) balloon valvuloplasty. Median TAVI-to-re-intervention time was 207 (35; 765) days. The failed valve was self-expanding in 129 (63.9%) patients. The most frequent devices utilized were a Sapien 3 valve for redo-TAVI (55, 64%), an AVP II as plug (33, 42%), and a True balloon for valvuloplasty (20, 56%). At 30 days, AR ≥ moderate persisted in 33 (17.4%) patients: 8 (9.9%) after redo-TAVI, 18 (25.9%) after plug, and 7 (21.9%) after valvuloplasty (P = 0.036). Overall mortality was 10 (5.0%) at 30 days and 29 (14.4%) at 1 year: 0, 8 (10.1%), and 2 (5.7%) at 30 days (P = 0.010) and 11 (12.6%), 14 (17.7%), and 4 (11.4%) at 1 year (P = 0.418), after redo-TAVI, plug, and valvuloplasty, respectively. Regardless of treatment strategy, patients in whom AR was reduced to ≤ mild had lower mortality at 1 year compared with those with AR persisting ≥ moderate [11 (8.0%) vs. 6 (21.4%); P = 0.007]., Conclusion: This study describes the efficacy of transcatheter treatments for PVR after TAVI. Patients in whom PVR was successfully reduced had better prognosis. The selection of patients and the optimal PVR treatment modality require further investigation., Competing Interests: Conflict of interest J.G.W.: consultant to, and has received research funding from, Edwards Lifesciences, Abbott Vascular, and Boston Scientific. W-K.K.: proctor or speaker fees from Boston Scientific, Abbott, Edwards Lifesciences, Medtronic, Meril Life Sciences. M.A-W.: received speaker's honoraria and/or consultancy fees on his behalf from Boston Scientific and Medtronic. M.B.: consultant for Edwards Lifesciences, Medtronic, and Boston Scientific. L.S.: consultant fees and institutional research grants from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and Symetis. C.H.: Advisory Board Medtronic. J.M. Sinning: speaker honoraria and research grants from Medtronic, Boston Scientific, and Edwards Lifesciences. J.S.: consultant to Edwards Lifesciences. M. Andreas: proctor/consultant/speaker for Edwards, Abbott, and Medtronic, received institutional grants (Edwards, Abbott, Medtronic, and LSI). Dr. M. Guerrero: research grant support from Abbott Vascular and Edwards Lifesciences. F. Castriota: proctor for Medtronic and Boston Scientific. T.N.: consulting or honoraria from Edwards Lifesciences, Medtronic, and Boston Scientific. Consulting and equity with Venus MedTech. T.P.: research grants from Boston Scientific, Edwards Lifesciences, and Biotronik; speaker fees/consultancy fees from Boston Scientific, Medtronic, Abbott, Biotronik, and HighLife SAS. V.C. Babaliaros: consultant to Edwards Lifesciences and equity in transmural system. M.M.: consultant fee from Abbott, Boston, Kardia, and Medtronic. N.V.M.: institutional research grants and consulting fees from Abbott, Boston Scientific, Medtronic, Daiichi Sankyo, and PulseCath BV and institutional research grant support from Edwards Lifesciences. A.L.: institutional research/grant support from Abbott, Boston Scientific, Medtronic, and Edwards Lifesciences; and personal consulting honoraria from Abbott, Edwards Lifesciences and Medtronic. D.H-S.: proctor and advisory to Boston, Medtronic, Edwards Lifesciences, and Abbott. R.M. received grant support from Edwards Lifesciences Corporation; he is a consultant for Abbott Vascular, Cordis, and Medtronic and holds equity in Entourage Medical. All other authors have no conflict of interest to report in relation with this manuscript., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The best management of stable coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI) is still unclear due to the marked inconsistency of the available evidence., Methods: The REVASC-TAVI registry (Management of Myocardial Revascularization in Patients Undergoing Transcatheter Aortic Valve Implantation With Coronary Artery Disease) collected data from 30 centers worldwide on patients undergoing TAVI who had significant, stable CAD at preprocedural work-up. For the purposes of this analysis, patients with either complete or incomplete myocardial revascularization were compared in a propensity score matched analysis, to take into account of baseline confounders. The primary and co-primary outcomes were all-cause death and the composite of all-cause death, stroke, myocardial infarction, and rehospitalization for heart failure, respectively, at 2 years., Results: Among 2407 patients enrolled, 675 pairs of patients achieving complete or incomplete myocardial revascularization were matched. The primary (21.6% versus 18.2%, hazard ratio' 0.88 [95% CI, 0.66-1.18]; P =0.38) and co-primary composite (29.0% versus 27.1%, hazard ratio' 0.97 [95% CI, 0.76-1.24]; P =0.83) outcome did not differ between patients achieving complete or incomplete myocardial revascularization, respectively. These results were consistent across different prespecified subgroups of patients (< or >75 years of age, Society of Thoracic Surgeons score > or <4%, angina at baseline, diabetes, left ventricular ejection fraction > or <40%, New York Heart Association class I/II or III/IV, renal failure, proximal CAD, multivessel CAD, and left main/proximal anterior descending artery CAD; all P values for interaction >0.10)., Conclusions: The present analysis of the REVASC-TAVI registry showed that, among TAVI patients with significant stable CAD found during the TAVI work-up, completeness of myocardial revascularization achieved either staged or concomitantly with TAVI was similar to a strategy of incomplete revascularization in reducing the risk of all cause death, as well as the risk of death, stroke, myocardial infarction, and rehospitalization for heart failure at 2 years, regardless of the clinical and anatomical situations.

Background: Transcatheter aortic valve implantation (TAVI) is the preferred treatment option for severe aortic stenosis in the elderly and in patients with comorbidities. We sought to compare outcomes after TAVI and surgical aortic valve replacement (SAVR) in octogenarians., Methods: In this retrospective cohort study conducted at our tertiary center, clinical data were gathered before and after TAVI and SAVR procedures performed from January 2013 to May 2019; follow-up completed in March 2021. The primary outcome was 1-year mortality. Patients were stratified according to Society of Thoracic Surgeons (STS) score and procedure type. Propensity score-based matching was also performed., Results: Of 542 patients who matched the inclusion criteria, 273 underwent TAVI and 269 SAVR. TAVI patients were older (85.8 ± 3.0 vs. 82.2 ± 2.2 years; P < 0.001) and had a higher mean STS score (5.0 ± 4.0 vs. 2.8 ± 1.3; P < 0.001) and EuroSCORE II (5.3 ± 4.1 vs. 2.8 ± 6.0; P < 0.001). Rates of postoperative permanent pacemaker insertion (15.0% vs. 9.3%; P = 0.040) and paravalvular leak (9.9% vs. 0.8%; P < 0.001) were higher and acute kidney injury lower (8.8% vs. 32.7%; P < 0.001) after TAVI, with no difference between treatment groups for major bleeding (11.0% vs. 6.7%; P = 0.130) or 30-day mortality (5.5% vs. 3.7%; P = 0.315). A statistically significant difference was found between TAVI and SAVR in low- and intermediate-risk groups when it came to occurrence of paravalvular leak, acute kidney injury, and new onset AF (all P < 0.001)., Conclusion: This analysis of an octogenarian "real-life" population undergoing TAVI or SAVR (with a biological valve) showed similar outcomes regarding clinical endpoints in low- and medium-risk (STS score) groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kolar, Lakič, Kotnik, Štubljar, Fras and Bunc.)

Background: The natural history of tricuspid valve regurgitation (TR) is characterized by poor prognosis and high in-hospital mortality when treated with isolated surgery. We report the preliminary echocardiographic and procedural results of a prospective cohort of symptomatic patients with high to prohibitive surgical risk and at least severe TR who underwent transcatheter edge-to-edge repair through the TriClipTM system. Methods: From June 2020 to March 2022, 27 consecutive patients were screened, and 13 underwent transcatheter TriClipTM repair. In-hospital, 30-day and six-month clinical and echocardiographic outcomes were collected. Results: Nine patients had severe, three massive and one baseline torrential TR. Sustained TR reduction of ≥1 grade was achieved in all patients, of which 90% reached a moderate TR or less. On transthoracic echocardiographic examination, there were significant reductions in vena contracta width (p < 0.001), effective regurgitant orifice area (p < 0.001) and regurgitant volume (p < 0.001) between baseline and hospital discharge. We also observed a significant reduction in tricuspid annulus diameter (p < 0.001), right ventricular basal diameter (p = 0.001) and right atrial area (p = 0.026). Conclusion: Treatment with the edge-to-edge TriClip device is safe and effective. The resulting echocardiographic improvements indicate tricuspid valve leaflet approximation does not just significantly reduce the grade of TR but also affects adjacent structures and improves right ventricular afterload adaptation.

Aortic stenosis is the most common valve disease requiring surgery or percutaneous treatment. Since the first-in-man implantation in 2002 we have witnessed incredible progress in transcatheter aortic valve implantation (TAVI). In this article, we review the technical aspects of TAVI development with a look at the future. Durability, low thrombogenicity, good hydrodynamics, biocompatibility, low catheter profile, and deployment stability are the attributes of an ideal TAVI device. Two main design types exist-balloon-expandable and self-expanding prostheses. Balloon-expandable prostheses use a cobalt-chromium alloy frame providing high radial strength and radiopacity, while the self-expanding prostheses use a nickel-titanium (Nitinol) alloy frame, which expands to its original shape once unsheathed and heated to the body temperature. The valve is sewn onto the frame and consists of the porcine or bovine pericardium, which is specially treated to prevent calcinations and prolong durability. The lower part of the frame can be covered by polyethylene terephthalate fabric or a pericardial skirt, providing better sealing between the frame and aortic annulus. The main future challenges lie in achieving lower rates of paravalvular leaks and new pacemaker implantations following the procedure, lower delivery system profiles, more precise positioning, longer durability, and a good hemodynamic profile. Patient-specific design and the use of autologous tissue might solve these issues.

Background: As transcatheter aortic valve (TAV) replacement is increasingly used in patients with longer life expectancy, a sizable proportion will require redo TAV replacement (TAVR). The unique configuration of balloon-expandable TAV (bTAV) vs a self-expanding TAV (sTAV) potentially affects TAV-in-TAV outcome., Objectives: The purpose of this study was to better inform prosthesis selection, TAV-in-TAV outcomes were assessed according to the type of initial and subsequent TAV., Methods: Patients from the Redo-TAVR registry were analyzed using propensity weighting according to their initial valve type (bTAV [n = 115] vs sTAV [n = 106]) and subsequent valve type (bTAV [n = 130] vs sTAV [n = 91])., Results: Patients with failed bTAVs presented later (vs sTAV) (4.9 ± 2.1 years vs 3.7 ± 2.3 years; P < 0.001), with smaller effective orifice area (1.0 ± 0.7 cm 2 vs 1.3 ± 0.8 cm 2 ; P = 0.018) and less frequent dominant regurgitation (16.2% vs 47.3%; P < 0.001). Mortality at 30 days was 2.3% (TAV-in-bTAV) vs 0% (TAV-in-sTAV) (P = 0.499) and 1.7% (bTAV-in-TAV) vs 1.0% (sTAV-in-TAV) (P = 0.612); procedural safety was 72.6% (TAV-in-bTAV) vs 71.2% (TAV-in-sTAV) (P = 0.817) and 73.2% (bTAV-in-TAV) vs 76.5% (sTAV-in-TAV) (P = 0.590). Device success was similar according to initial valve type but higher with subsequent sTAV vs bTAV (77.2% vs 64.3%; P = 0.045), primarily because of lower residual gradients (10.3 mm Hg [8.9-11.7 mm Hg] vs 15.2 mm Hg [13.2-17.1 mm Hg]; P < 0.001). Residual regurgitation (moderate or greater) was similar after bTAV-in-TAV and sTAV-in-TAV (5.7%) and nominally higher after TAV-in-bTAV (9.1%) vs TAV-in-sTAV (4.4%) (P = 0.176)., Conclusions: In selected patients, no association was observed between TAV type and redo TAVR safety or mortality, yet subsequent sTAV was associated with higher device success because of lower redo gradients. These findings are preliminary, and more data are needed to guide valve choice for redo TAVR., Competing Interests: Funding Support and Author Disclosures Dr Webb is a consultant to and has received research funding from Edwards Lifesciences, Abbott Vascular, and Boston Scientific. Dr Kim is a proctor for and has received speaker fees from Boston Scientific, Abbott, Edwards Lifesciences, and Medtronic. Dr Abdel-Wahab has received speaker honoraria and/or consultancy fees to the hospital on his behalf from Boston Scientific and Medtronic. Dr Barbanti is a consultant for Edwards Lifesciences; and is an advisory board member for Biotronik. Dr Søndergaard has received consulting fees and institutional research grants from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and Symetis. Dr Redwood is a proctor for and has received lecture fees from Edwards Lifesciences. Dr Hamm is an advisory board member for Medtronic. Dr Sinning has received speaker honoraria and research grants from Medtronic, Boston Scientific, and Edwards Lifesciences. Dr Sathananthan is a consultant to Edwards Lifesciences. Dr Schofer has received speaker fees and travel compensation from Boston Scientific; and has received travel compensation from Edwards Lifesciences and Abbott/St. Jude Medical. Dr Andreas is a proctor, consultant, and speaker for Edwards Lifesciences, Abbott, and Medtronic; and has received institutional grants from Edwards Lifesciences, Abbott, Medtronic, and LSI. Dr Guerrero has received research grant support from Abbott Vascular and Edwards Lifesciences. Dr Castriota is a proctor for Medtronic and Boston Scientific. Dr Nazif is a consultant for or has received honoraria from Edwards Lifesciences, Medtronic, Boston Scientific, Biotrace, and Baylis Medical; and is a consultant for and holds equity in Venus Medtech. Dr Pilgrim has received research grants from Boston Scientific, Edwards Lifesciences, and Biotronik; and has received speaker fees from Boston Scientific and Biotronik. Dr Babaliaros is a consultant to Edwards Lifesciences; and holds equity in Transmural Systems. Dr Van Mieghem has received institutional research grants and consulting fees from Abbott, Boston Scientific, Medtronic, Daiichi Sankyo, and PulseCath; and has received institutional research grant support from Edwards Lifesciences. Dr Latib has received institutional research and grant support from Abbott, Boston Scientific, Medtronic, and Edwards Lifesciences; and has received personal consulting honoraria from Abbott, Edwards Lifesciences, and Medtronic. Dr Hildick-Smith is a proctor and adviser for Boston Scientific, Medtronic, and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Background: Data on outcomes of transcatheter aortic valve replacement (TAVR) using balloon-expandable valves (BEVs) or self-expandable valves (SEVs) as well as the impact of center valve preference on these outcomes are limited., Objectives: The aim of this study was to compare outcomes of TAVR procedures using third-generation BEVs and SEVs stratified by center valve preference., Methods: In a multicenter registry (n = 17), 13 centers exhibited valve preference (66.6%-90% of volume) and were included. Outcomes were compared between BEVs and SEVs stratified by center valve preference., Results: In total, 7,528 TAVR procedures (3,854 with SEVs and 3,674 with BEVs) were included. The mean age was 81 years, and the mean Society of Thoracic Surgeons score was 5.2. Baseline characteristics were similar between BEVs and SEVs. Need for pacemaker implantation was higher with SEVs at BEV- and SEV-dominant centers (17.8% vs 9.3% [P < 0.001] and 12.7% vs 10.0% [P = 0.036], respectively; HR: 1.51; P for interaction = 0.021), risk for cerebrovascular accident was higher with SEVs at BEV-dominant but not SEV-dominant centers (3.6% vs 1.1% [P < 0.001] and 2.2% vs 1.4% [P = 0.162]; HR: 2.08; P for interaction < 0.01). Aortic regurgitation greater than mild was more frequent with SEVs at BEV-dominant centers and similar with BEVs regardless of center dominance (5.2% vs 2.8% [P < 0.001] and 3.4% vs 3.7% [P = 0.504], respectively). Two-year mortality was higher with SEVs at BEV-dominant centers but not at SEV-dominant centers (21.9% vs 16.9% [P = 0.021] and 16.8% vs 16.5% [P = 0.642], respectively; HR: 1.20; P for interaction = 0.032)., Conclusions: Periprocedural outcomes, aortic regurgitation greater than mild, and 2-year mortality are worse when TAVR is performed using SEVs at BEV-dominant centers. Outcomes are similar regardless of valve type at SEV-dominant centers. The present results stress the need to account for this factor when comparing BEV and SEV outcomes. (The Aortic+Mitral Transcatheter [AMTRAC] Valve Registry; NCT04031274)., Competing Interests: Funding Support and Author Disclosures Dr Van Miegham has received research grant support from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, PulseCath BV, and Daiichi-Sankyo; and has received advisory fees from Abbott, Boston Scientific, Ancora, Medtronic, PulseCath BV, and Daiichi-Sankyo. Dr Barbanti has received consulting fees from Edwards Lifesciences. Dr Grasso is a proctor for Abbott Vascular. Dr De Backer has received research grants and consulting fees from Abbott and Boston Scientific. Dr Andreas is a proctor for Abbott and Edwards Lifesciences; and has received advisory board fees from Medtronic. Dr Estévez-Loureiro is a consultant for Abbott Vascular and Boston Scientific. Dr Nombela-Franco has received consulting fees from Edwards Lifesciences; and is a proctor for Abbott. Dr Søndergaard has received consulting fees and/or institutional research support from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, and SMT. Dr Amat-Santos is a proctor for Boston Scientific. Dr Finkelstein is a proctor for Edwards Lifesciences and Medtronic; and has received consulting fees from Edwards Lifesciences and Medtronic. 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.)

Introduction: Severe aortic stenosis, a highly-common valve disease in the elderly, has a poor prognosis if left untreated. To address the concern of effective procedures for severe aortic stenosis, a systematic TAVI program was established at the Dedinje Cardiovascular Institute (Belgrade, Serbia)., Methods: Our cohort was composed of 56 patients (74±15 years old). The mean logistic EuroScore was 10.17%; the mean Society of Thoracic Surgeons score was 3.22%. One third of the patients were categorized as class III or IV of the New York Heart Association (NYHA). The valves selected for use were either self-expandable or balloon expandable (Evolut R, Medtronic; Acurate Neo, Boston Scientific and Myval, Meril). The choice of valve type was made by the Institute's Structural Heart Team, in accordance with the patient's native aortic valve, size and calcification of ilio-femoral vessels, as well as the need for alternative access. TAVI procedure was conducted according to current guidelines provided by the European Society of Cardiology., Results: The procedure success rate was 100%. Trans-femoral approach was achieved in 100% of patients; percutaneously in 87.5%, while a surgical cut was necessary in 12.5%. No patient showed moderate or severe aortic regurgitation after the procedure, although trace or mild regurgitation was recorded in 30.3%. Permanent pacemaker was implanted in one patient (1.78%), contrast induced acute kidney injury occured in one patient (1.78%), no stroke was recorded, and three pseudo-aneurysms which required surgical intervention occurred. Three patients required blood transfusions (5.33%). A 30-day all-cause mortality rate was 1.78%., Conclusion: The Dedinje Cardiovascular Institute spearheaded all efforts to establish a TAVI program in Serbia. Our initial TAVI results are promising, encouraging, and comparable with the results of previous large randomized trials. This initial experience opens the door for further development with a goal of our Institute to become a high-volume TAVI center., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Boljevic, Bojic, Farkic, Sagic, Topic, Kovacevic, Lakcevic, Veljkovic, Dobric, Hinic, Ilijevski, Nikolic, Kaludjerovic, Bunc and Nikolic.)

Background: The mean age of transcatheter aortic valve implantation (TAVI) patients is steadily decreasing., Aims: The aim of the study was to describe the characteristics, the indications for and the outcomes of TAVI in patients <70 years old., Methods: All patients undergoing TAVI (n=8,626) from the 18 participating centres between January 2007 and June 2020 were stratified by age (70). For patients <70, the indications for TAVI were extracted from Heart Team discussions and the baseline characteristics and mortality were compared between the two groups., Results: Overall, 640 (7.4%) patients were <70 (9.1% during 2018-2020, p<0.001); the mean age was 65.0±2.3 years. The younger patients were more often male, with bicuspid valves or needing valve-in-valve procedures. They had a higher prevalence of lung disease and diabetes. In 80.7% of cases, the Heart Team estimated an increased surgical risk and TAVI was selected, reflected by an STS score >4% in 20.4%. Five-year mortality was similar (29.4 vs 29.8%, HR 0.95, p=0.432) in the <70 and >70 groups. In the <70 group, mortality was higher for those referred for TAVI due to an increased surgical risk compared to those referred for other reasons (31.6 vs 24.5%, HR 1.23, p=0.021). Mortality was similar regardless of the STS stratum in patients judged by the Heart Team to be at increased surgical risk (32.6 vs 30.4%, HR 0.98, p=0.715)., Conclusions: Use of TAVI in patients <70 is becoming more frequent. The main reason for choosing TAVI is due to an increased surgical risk not adequately represented by the STS score. The outcomes for these patients are similar to those for older TAVI patients. Dedicated trials of TAVI/SAVR in younger patients are needed to guide decisions concerning expansion of TAVI indications. ((ClinicalTrials.gov: NCT04031274).

Monoclonal antibodies are the fastest growing class of therapeutics. However, aggregation limits their shelf life and can lead to adverse immune responses. Assessment and optimization of the long-term antibody stability are therefore key challenges in the biologic drug development. Here, we present a platform based on the analysis of temperature-dependent aggregation data that can dramatically shorten the assessment of the long-term aggregation stability and thus accelerate the optimization of antibody formulations. For a set of antibodies used in the therapeutic areas from oncology to rheumatology and osteoporosis, we obtain an accurate prediction of aggregate fractions for up to three years using the data obtained on a much shorter time scale. Significantly, the strategy combining kinetic and thermodynamic analysis not only contributes to a better understanding of the molecular mechanisms of antibody aggregation but has already proven to be very effective in the development and production of biological therapeutics.

Background: Clinical efficacy of coronary sinus reducer (CSR) in refractory angina (RA) patients with ischemia due to the chronic total occlusion (CTO) of the right coronary artery (RCA) remains unknown., Aims: To evaluate the efficacy of CSR implantation in RA patients with CTO RCA and compare them to CSR recipients with left coronary artery (LCA) ischemia., Methods: Consecutive patients with CTO RCA from 2 centers were prospectively included and compared to patients with LCA ischemia. All patients underwent evaluation of angina severity and quality of life (QoL) at baseline and after 12 months. In a subgroup of CTO RCA patients, stress cardiac magnetic resonance (CMR) imaging was also performed., Results: Twenty-two patients with CTO RCA and predominant inferior and/or inferoseptal wall ischemia (the CTO RCA group) were compared to 24 patients with predominant anterior, lateral, and/or anteroseptal wall ischemia (the LCA group). While the Canadian Cardiovascular Society (CCS) anginascore mean (SD) improved in the CTO RCA group from 2.73 (0.46) to 1.82 (0.73) (P <0.001) and in the LCA group from 2.67 (0.57) to 1.92 (0.72) (P <0.001), there was no intergroup difference (P = 0.350). Significant improvement in all domains of the Seattle Angina Questionnaire was observed. Stress CMR did not show a significant reduction of ischemic inferior and/or inferoseptal segments, however, improvements in the transmurality index (P = 0.03) and the myocardial perfusion reserve index in segments with inducible ischemia (P = 0.03) were observed in the CTO RCA group., Conclusions: In CTO RCA patients, CSR implantation alleviated angina symptoms and improved QoL. The extent of improvement was comparable to that observed in patients with LCA ischemia.