Abstract
Aims: The Valve Academic Research Consortium (VARC), founded in 2010, was intended to (i) identify appropriate clinical endpoints and (ii) standardize definitions of these endpoints for transcatheter and surgical aortic valve clinical trials. Rapid evolution of the field, including the emergence of new complications, expanding clinical indications, and novel therapy strategies have mandated further refinement and expansion of these definitions to ensure clinical relevance. This document provides an update of the most appropriate clinical endpoint definitions to be used in the conduct of transcatheter and surgical aortic valve clinical research. Methods and results: Several years after the publication of the VARC-2 manuscript, an in-person meeting was held involving over 50 independent clinical experts representing several professional societies, academic research organizations, the US Food and Drug Administration (FDA), and industry representatives to (i) evaluate utilization of VARC endpoint definitions in clinical research, (ii) discuss the scope of this focused update, and (iii) review and revise specific clinical endpoint definitions. A writing committee of independent experts was convened and subsequently met to further address outstanding issues. There were ongoing discussions with FDA and many experts to develop a new classification schema for bioprosthetic valve dysfunction and failure. Overall, this multi-disciplinary process has resulted in important recommendations for data reporting, clinical research methods, and updated endpoint definitions. New definitions or modifications of existing definitions are being proposed for repeat hospitalizations, access site-related complications, bleeding events, conduction disturbances, cardiac structural complications, and bioprosthetic valve dysfunction and failure (including valve leaflet thickening and thrombosis). A more granular 5-class grading scheme for paravalvular regurgitation (PVR) is being proposed to help refine the assessment of PVR. Finally, more specific recommendations on quality-of-life assessments have been included, which have been targeted to specific clinical study designs. Conclusions: Acknowledging the dynamic and evolving nature of less-invasive aortic valve therapies, further refinements of clinical research processes are required. The adoption of these updated and newly proposed VARC-3 endpoints and definitions will ensure homogenous event reporting, accurate adjudication, and appropriate comparisons of clinical research studies involving devices and new therapeutic strategies.
| Original language | English |
|---|---|
| Pages (from-to) | 2717-2746 |
| Number of pages | 30 |
| Journal | Journal of the American College of Cardiology |
| Volume | 77 |
| Issue number | 21 |
| DOIs | |
| Publication status | Published - 1 Jun 2021 |
Bibliographical note
Funding Information:The authors wish to thank the following individuals, who made significant contributions to the development of this document: Stuart J. Head, MD, PhD (Medtronic, Inc.), A. Pieter Kappetein, MD, PhD (Medtronic), Neil E. Moat, MD (Abbott), and Bahira Shahim, MD, PhD (Cardiovascular Research Foundation).
Funding Information:
P.G. has received consultant fees from Abbott Vascular, Abiomed, Boston Scientific, Cardinal Health, Cardiovascular System Inc., Edwards Lifesciences, Medtronic, Opsens, Siemens, SoundBite Medical Solutions, Sig.Num, Saranas, Teleflex, Tryton Medical, and has equity in Pi-Cardia, Sig.Num, SoundBite Medical Solutions, Saranas, and Puzzle Medical. N.P. has received consultant fees from Medtronic, Peijia, and Microport. M.C.A.’s institution receives research funding from Edwards Lifesciences and Abbott. T.N. discloses consulting fees or honoraria from Edwards LifeSciences, Medtronic, Boston Scientific, and Biotrace Medical and consulting fees and equity from Keystone Heart. R.T.H. reports speaker fees from Boston Scientific Corporation and Baylis Medical; consulting for Abbott Structural, Edwards Lifesciences, Medtronic, Navigate, Philips Healthcare and Siemens Healthcare; non-financial support from 3mensio; and is the Chief Scientific Officer for the Echocardiography Core Laboratory at the Cardiovascular Research Foundation for multiple industry-sponsored trials, for which she receives no direct industry compensation. P.P. received research grants from Edwards Lifesciences and Medtronic for echo corelab analyses in TAVR. J.B. reports personal fees from Abbott Vascular and Boehringer Ingelheim, and grants from Edwards, Boston Scientific, General Electric, Biotronik, and Medtronic, all outside the submitted work. J.L. reports personal fees from Circle CVI, GE Healthcare, Philips and HeartFlow, as well as grants to his institution for core lab work from Medtronic, Edwards, Abbott, and GE Healthcare. E.H.B. reports grants to his institution from Edwards Lifesciences. A.L. reports grants from Novartis and Edwards Lifesciences, personal fees from Medtronic, Abbott, Edwards, Boston Scientific, AstraZeneca, Novartis, Pfizer, Abiomed, Bayer, Boehringer, and stock options from Picardia, Transverse Medical, and Claret Medical. M.M. reports grants from Abbott, Medtronic, and Edwards. R.M. reports grants from Abbott and Edwards Lifesciences, and personal fees from Cordis and Medtronic. R.M. reports grants, personal fees, and other from Abbott Laboratories, grants from AstraZeneca, Bayer, and Beth Israel Deaconess, grants and other from Bristol-Myers Squibb, grants from CERC, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, and OrbusNeich, grants and other from Abiomed, other from the Medicines Company, personal fees from Boston Scientific, personal fees from Janssen Scientific Affairs, Medscape/WebMD, Roivant Services, Sanofi, Siemens Medical Solutions, and non-financial support and other from Idorsia Pharmaceuticals, non-financial support and other from Regeneron Pharmaceuticals, other from Spectranetics/Philips/Volcano Corp, personal fees from Medtelligence (Janssen Scientific Affairs), other from Watermark Research Partners, other from Claret Medical, other from Elixir Medical, personal fees from ACC, personal fees from AMA, grants from Applied Therapeutics, other from Merck, outside the submitted work. J.P.P. reports grants from Medtronic, grants and personal fees from Edwards, grants from Boston Scientific, grants from Abbott, outside the submitted work. M.R. reports consulting for Medtronic, with fees to his institution. J.R.-C. has received institutional research grants from Edwards Lifesciences, Medtronic and Boston Scientific. Nicolas Van Mieghem has received research grants from Abbott, Boston Scientific, Edwards, Medtronic and Essential Medical/Teleflex. He received advisory fees from Abbott, Boston Scientific, Ancora, Medtronic and Essential Medical/Teleflex. J.G.W. has received consulting fees from Edwards Lifesciences. D.J.C. reports institutional research grants and personal fees from Edwards Lifesciences, grants and personal fees from Medtronic, grants and personal fees from Boston Scientific, grants and personal fees from Abbott, outside the submitted work. M.B.L. reports institutional research grants from Edwards Lifesciences, Medtronic, Boston Scientific and Abbott, and advisory board/consulting fees from Medtronic, Boston Scientific, Abbott, Gore Medical and Meril Lifescience, all outside the submitted work.
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