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Objectives: The aim of this study was to characterize the safety profile of an intra-annular self-expanding valve with a next-generation low-profile delivery system (DS)., Background: Key design modifications to the FlexNav DS include the addition of a hydrophilic-coated, integrated sheath and stability layer to facilitate gradual, controlled deployment in vessels with diameter ≥5 mm., Methods: Patients were pooled from 2 concurrent prospective, multicenter, single-arm studies (FlexNav DS arm of PORTICO IDE [Portico Re-Sheathable Transcatheter Aortic Valve System U.S. IDE Trial] [n = 134] and the FlexNav EU CE Mark Study [n = 46]) for the analysis. The primary endpoint was Valve Academic Research Consortium-2-defined major vascular complications at 30 days. Clinical outcomes and valve performance were assessed through 30 days by an independent clinical events committee and an echocardiography core laboratory, respectively., Results: One hundred forty high-risk and 40 extreme-risk subjects enrolled between October 15, 2018, and December 10, 2019, from 28 sites in the United States, Australia, and Europe who underwent attempted transfemoral Portico valve implantation were included. The mean age was 85.1 ± 5.6 years, 60% were women, the mean Society of Thoracic Surgeons score was 5.3%, and 96.1% presented with ≥1 frailty factor. Technical device success was 96.7%. At 30 days, the rate of major vascular complications was 5.0%, with 4.4% of complications adjudicated as access site-related (3.3% transcatheter aortic valve replacement DS access site-related). Death (0.6%) and disabling stroke (1.1%) were rare. The rate of new permanent pacemaker implantation was 15.4%. Echocardiography revealed a mean gradient of 7.1 ± 3.2 mm Hg, mean valve area of 1.77 ± 0.41 cm 2 , and a 4.1% rate of moderate paravalvular leak at 30 days., Conclusions: Portico valve implantation with the FlexNav DS was associated with an excellent safety profile at 30 days., Competing Interests: Author Relationship With Industry Dr. Fontana is a consultant for and has received proctoring fees from Abbott, Medtronic, and LivaNova; is a member of the structural heart safety advisory board for Abbott; and is a principal investigator for Abbott and Medtronic. Dr. Bedogni has served as a consultant for Boston Scientific, Medtronic, and Abbott. Dr. Groh is a member of the structural heart safety advisory board for Abbott. Dr. Smith has received speaking fees and proctoring fees from Abbott. Dr. Chehab has received grant and research support from Abbott; and has received speaking and proctoring fees from Abbott, Edwards Lifesciences, Medtronic, and Boston Scientific. Dr. Yong is a physician proctor for Abbott Vascular, Medtronic, and Edwards Lifesciences. Dr. Worthley has received research grants from Abbott and Biotronik. Dr. Manoharan has served as a proctor for Boston Scientific, Medtronic, and Abbott. Dr. Walton is a proctor for Medtronic and Abbott; is a medical advisory board member for Medtronic; and has received grant support from Medtronic, Abbott, and Edwards Lifesciences. Dr. Hermiller is a physician proctor for Abbott. Dr. Dhar is a proctor for Abbott Vascular, Edwards Lifesciences, and Medtronic; has received a research grant from Boston Scientific; is a member of the interventional cardiology medical advisory board for Boston Scientific; and is a member of the Speakers Bureau for Boston Scientific. Dr. Waksman is an advisory board member for Amgen, Boston Scientific, Cardioset, Cardiovascular Systems, Medtronic, Philips, and Pi-Cardia; is a consultant for Amgen, Biotronik, Boston Scientific, Cardioset, Cardiovascular Systems, Medtronic, Philips, and Pi-Cardia; has received grant support from AstraZeneca, Biotronik, Boston Scientific, and Chiesi; is a Speakers Bureau member for AstraZeneca and Chiesi; and is an investor in MedAlliance. Dr. Ramana has received speaking, consulting, and proctoring fees from Edwards Lifesciences; has received consulting fees from Abbott and Medtronic; and has received research support from Boston Scientific. Dr. Mahoney is a consultant and proctor for Edwards Lifesciences; and is a consultant for Abbott. Dr. Asch is director of an academic echocardiography core laboratory that has institutional research contracts with Abbott, Edwards Lifesciences, Boston Scientific, Medtronic, LivaNova, Biotronik, and Vascular Innovations. Dr. Chakravarty is a consultant for Edwards Lifesciences, Medtronic, Abbott, and Boston Scientific. Dr. Jilaihawi has been a consultant to Boston Scientific and Medtronic; and has received grant and research support from Medtronic, Edwards Lifesciences, Abbott Vascular, and HLT, Inc. Dr. Makkar has received research grants and speaking and proctoring fees from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific. Dr. Garrett has reported that he has no relationships relevant to the contents of this paper to disclose., (Copyright © 2020. Published by Elsevier Inc.)

Background: Randomised trial data assessing the safety and efficacy of the self-expanding intra-annular Portico transcatheter aortic valve system (Abbott Structural Heart, St Paul, MN, USA) compared with any commercially available valves are needed to compare performance among designs., Methods: In this prospective, multicentre, non-inferiority, randomised controlled trial (the Portico Re-sheathable Transcatheter Aortic Valve System US Investigational Device Exemption trial [PORTICO IDE]), high and extreme risk patients with severe symptomatic aortic stenosis were recruited from 52 medical centres experienced in performing transcatheter aortic valve replacement in the USA and Australia. Patients were eligible if they were aged 21 years or older, in New York Heart Association functional class II or higher, and had severe native aortic stenosis. Eligible patients were randomly assigned (1:1) using permuted block randomisation (block sizes of 2 and 4) and stratified by clinical investigational site, surgical risk cohort, and vascular access method, to transcatheter aortic valve replacement with the first generation Portico valve and delivery system or a commercially available valve (either an intra-annular balloon-expandable Edwards-SAPIEN, SAPIEN XT, or SAPIEN 3 valve [Edwards LifeSciences, Irvine, CA, USA]; or a supra-annular self-expanding CoreValve, Evolut-R, or Evolut-PRO valve [Medtronic, Minneapolis, MN, USA]). Investigational site staff, implanting physician, and study participant were unmasked to treatment assignment. Core laboratories and clinical event assessors were masked to treatment allocation. The primary safety endpoint was a composite of all-cause mortality, disabling stroke, life-threatening bleeding requiring transfusion, acute kidney injury requiring dialysis, or major vascular complication at 30 days. The primary efficacy endpoint was all-cause mortality or disabling stroke at 1 year. Clinical outcomes and valve performance were assessed up to 2 years after the procedure. Primary analyses were by intention to treat and the Kaplan-Meier method to estimate event rates. The non-inferiority margin was 8·5% for primary safety and 8·0% for primary efficacy endpoints. This study is registered with ClinicalTrials.gov, NCT02000115, and is ongoing., Findings: Between May 30 and Sept 12, 2014, and between Aug 21, 2015, and Oct 10, 2017, with recruitment paused for 11 months by the funder, we recruited 1034 patients, of whom 750 were eligible and randomly assigned to the Portico valve group (n=381) or commercially available valve group (n=369). Mean age was 83 years (SD 7) and 395 (52·7%) patients were female. For the primary safety endpoint at 30 days, the event rate was higher in the Portico valve group than in the commercial valve group (52 [13·8%] vs 35 [9·6%]; absolute difference 4·2, 95% CI -0·4 to 8·8 [upper confidence bound {UCB} 8·1%]; p non-inferiority =0·034, p superiority =0·071). At 1 year, the rates of the primary efficacy endpoint were similar between the groups (55 [14·8%] in the Portico group vs 48 [13·4%] in the commercial valve group; difference 1·5%, 95% CI -3·6 to 6·5 [UCB 5·7%]; p non-inferiority =0·0058, p superiority =0·50). At 2 years, rates of death (80 [22·3%] vs 70 [20·2%]; p=0·40) or disabling stroke (10 [3·1%] vs 16 [5·0%]; p=0·23) were similar between groups., Interpretation: The Portico valve was associated with similar rates of death or disabling stroke at 2 years compared with commercial valves, but was associated with higher rates of the primary composite safety endpoint including death at 30 days. The first-generation Portico valve and delivery system did not offer advantages over other commercially available valves., Funding: Abbott., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Importance: To our knowledge, REPRISE III is the first large randomized comparison of 2 different transcatheter aortic valve replacement platforms: the mechanically expanded Lotus valve (Boston Scientific) and self-expanding CoreValve (Medtronic)., Objective: To evaluate outcomes of Lotus vs CoreValve after 2 years., Design, Setting, and Participants: A total of 912 patients with high/extreme risk and severe, symptomatic aortic stenosis enrolled between September 22, 2014, and December 24, 2015, were randomized 2:1 to receive Lotus (607 [66.6%]) or CoreValve (305 [33.4%] at 55 centers in North America, Europe, and Australia. The first 2-year visit occurred on October 17, 2016, and the last was conducted on April 12, 2018. Clinical and echocardiographic assessments are complete through 2 years and will continue annually through 5 years., Main Outcomes and Measures: All-cause mortality and all-cause mortality or disabling stroke at 2 years. Other clinical factors included overall stroke, disabling stroke, repeated procedures, rehospitalization, valve thrombosis, and pacemaker implantation. Echocardiographic analyses included effective orifice area, mean gradient, and paravalvular leaks (PVLs)., Results: Of 912 participants, the mean (SD) age was 82.8 (7.3) years, 465 (51%) were women, and the mean (SD) Society of Thoracic Surgeons predicted risk of mortality was 6.8% (4.0%). At 2 years, all-cause death was 21.3% with Lotus vs 22.5% with CoreValve (hazard ratio [HR], 0.94; 95% CI, 0.69-1.26; P = .67) and all-cause mortality or disabling stroke was 22.8% with Lotus and 27.0% with CoreValve (HR, 0.81; 95% CI, 0.61-1.07; P = .14). Overall stroke was 8.4% vs 11.4% (HR, 0.75; 95% CI, 0.48-1.17; P = .21); disabling stroke was more frequent with CoreValve vs Lotus (4.7% Lotus vs 8.6% CoreValve; HR, 0.53; 95% CI, 0.31-0.93; P = .02). More Lotus patients received a new permanent pacemaker (41.7% vs 26.1%; HR, 1.87; 95% CI, 1.41-2.49; P < .01) or had a valve thrombosis (3.0% vs 0.0%; P < .01) compared with CoreValve. More patients who received CoreValve experienced a repeated procedure (0.6% Lotus vs 2.9% CoreValve; HR, 0.19; 95% CI, 0.05-0.70; P < .01), valve migration (0.0% vs 0.7%; P = .05), or embolization (0.0% vs 2.0%; P < .01) than Lotus. Valve areas remained significantly larger and the mean gradient was lower with CoreValve than Lotus (valve area, mean [SD]: Lotus, 1.53 [0.49] cm2 vs CoreValve, 1.76 [0.51] cm2; P < .01; valve gradient, mean [SD]: Lotus, 13.0 [6.7] mm Hg vs 8.1 [3.7] mm Hg; P < .01). Moderate or greater PVL was more frequent with CoreValve (0.3% Lotus vs 3.8% CoreValve; P < .01) at 2 years. Larger improvements in New York Heart Association (NYHA) functional class were observed with Lotus compared with CoreValve (improved by ≥1 NYHA class: Lotus, 338 of 402 [84.1%] vs CoreValve, 143 of 189 [75.7%]; P = .01; improved by ≥2 NYHA classes: 122 of 402 [37.3%] vs 65 of 305 [21.3%])., Conclusions and Relevance: After 2 years, all-cause mortality rates, mortality or disabling stroke were similar between Lotus and CoreValve. Disabling stroke, functional class, valve migration, and PVL favored the Lotus arm whereas valve hemodynamics, thrombosis, and new pacemaker implantation favored the CoreValve arm., Trial Registration: clinicaltrials.gov Identifier: NCT02202434.