Clinical Research on Transcatheter Aortic Valve Replacement for Bicuspid Aortic Valve Disease: Principles, Challenges, and an Agenda for the Future.

Bicuspid aortic valve disease (BAVD) is present in up to half of all patients referred for surgical aortic valve replacement (SAVR) yet was an exclusion criterion for all randomized controlled trials (RCTs) comparing transcatheter aortic valve replacement (TAVR) to SAVR. Nonetheless, approximately 10% of patients currently treated with TAVR have BAVD and available observational data for performing TAVR in these patients are limited by selection bias. Many in the cardiovascular community have advocated for RCTs in this population, but none have been performed. The Heart Valve Collaboratory (HVC) is a multidisciplinary community of stakeholders with the aim of creating significant advances in valvular heart disease by stimulating clinical research, engaging in educational activities, and advancing regulatory science. In December 2020, the HVC hosted a Global Multidisciplinary workshop involving over 100 international experts in the field. Following this 2-day symposium, working groups with varied expertise were convened to discuss BAVD, including the need for and design of RCTs. This review, conducted under the auspices of the HVC, summarizes available data and knowledge gaps regarding procedural therapy for BAVD, outlining specific challenges for trials in this population. We also propose several potential studies that could be performed and discuss respective strengths and weaknesses of each approach. Finally, we present a roadmap for future directions in clinical research in TAVR for BAVD with an emphasis both on RCTs and also prospective registries focused on disease phenotyping to develop parameters and risk scores that could ultimately be applied to patients to inform clinical decision-making.
Competing Interests: Dr Madhavan was supported by a grant from the National Institutes of Health/National Heart, Lung, and Blood Institute to Columbia University Irving Medical Center (T32 HL007854). Dr Baron reports consulting for Boston Scientific Corp, Abiomed, Abbott, Edwards, and Mitra Labs and research support from Abiomed and Boston Scientific Corp. Dr Forrest is a consultant for Edwards Lifesciences and Medtronic and receives grant support from Edwards Lifesciences, and Medtronic. Dr Leipsic reports unrestricted research grants from GE Healthcare, stock options and consulting fees from HeartFlow and Circle CVI, payment or honoraria from Philips, board of directors of SCCT, deputy editor for Radiology: Cardiothoracic Imaging. Dr Cavalcante has received research grants from and is a consultant for Abbott Vascular, Circle Cardiovascular Imaging, Boston Scientific, Medtronic, Siemens Healthineers, and Edwards Lifesciences; is a consultant for VDyne and Triflo; and is a member of the Speakers Bureau for Circle Cardiovascular Imaging, Medtronic, Siemens Healthineers. Dr Wang has served as a consultant to Edwards Lifesciences, Abbott, NeoChord, and Boston Scientific; and received research grant support from Boston Scientific assigned to her employer, the Henry Ford Health System. Dr McCarthy has received royalties and honoraria for speaking for Edwards Lifesciences. Dr Szerlip has served as National Principal Investigator for trial sponsored by Edwards Lifesciences; has served on steering committees for trials by Abbott and Medtronic; and has served as speaker for Medtronic, Abbott, and Edwards Lifesciences. Dr Makkar has received research grants from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific; has served as national Principal Investigator for Portico (Abbott) and Acurate (Boston Scientific) U.S. investigation device exemption trials; has received personal proctoring fees from Edwards Lifesciences; and has received travel support from Edwards Lifesciences, Abbott, and Boston Scientific. Dr Mack has served as a co-principal investigator for Edwards Lifesciences and Abbott; and as a study chair for Medtronic. Dr Leon has received research support to his institution from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott; has served on Advisory Boards for Medtronic, Boston Scientific, Gore, Meril Lifescience, and Abbott; and has served as the Co-Principal Investigator of the PARTNER 3 trial (Edwards Lifesciences, no direct compensation). Dr Cohen has received institutional research grants and personal fees from Medtronic, Boston Scientific, and Abbott Vascular, outside the submitted work. The other authors had no conflicts to declare.
(© 2022 The Author(s).)