Philippe Généreux1, Nicolo Piazza2, Maria C Alu3, Tamim Nazif3, Rebecca T Hahn3, Philippe Pibarot4, Jeroen J Bax5, Jonathon A Leipsic6, Philipp Blanke6, Eugene H Blackstone7, Matthew T Finn3, Samir Kapadia8, Axel Linke9, Michael J Mack10, Raj Makkar11, Roxana Mehran12, Jeffrey J Popma13, Michael Reardon14, Josep Rodes-Cabau4, Nicolas M Van Mieghem15, John G Webb16, David J Cohen17, Martin B Leon18. 1. Gagnon Cardiovascular Institute, Morristown Medical Center, Morristown, New Jersey, USA. 2. McGill University Health Centre, Montreal, Quebec, Canada. 3. Columbia University Irving Medical Center/NewYork-Presbyterian Hospital and Cardiovascular Research Foundation, New York, New York, USA. 4. Quebec Heart & Lung Institute, Laval University, Quebec, Quebec, Canada. 5. Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. 6. Department of Radiology, St. Paul's Hospital and University of British Columbia, Vancouver, British Columboa, Canada. 7. Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic and Department of Quantitative Health Sciences, Research Institute, Cleveland Clinic, Cleveland, Ohio, USA. 8. Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. 9. Herzzentrum Dresden, Dresden, Germany. 10. Baylor Scott & White Heart Hospital Plano, Plano, Texas, USA. 11. Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. 12. The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 13. Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. 14. Methodist DeBakey Heart & Vascular Center, Houston, Texas, USA. 15. Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands. 16. Department of Cardiology, St. Paul's Hospital and University of British Columbia, Vancouver, British Columnia, Canada. 17. University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA. 18. Columbia University Irving Medical Center/NewYork-Presbyterian Hospital and Cardiovascular Research Foundation, New York, New York, USA. Electronic address: ml2398@columbia.edu.
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.
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.
Authors: Madeleine Barker; Janarthanan Sathananthan; Emily Perdoncin; Chandan Devireddy; Patricia Keegan; Kendra Grubb; Andrei M Pop; Jeremiah P Depta; Devesh Rai; Farhad Abtahian; Mark S Spence; Jonathan Mailey; Douglas F Muir; Mark J Russo; Jennifer Pineda-Salazar; Alexis Okoh; Meghan Smith; Thom G Dahle; Masud Rana; Mesfer Alfadhel; David Meier; Andrew Chatfield; Mariama Akodad; Anthony Chuang; Rohit Samuel; Thomas Nestelberger; Cameron McAlister; Sandra Lauck; John G Webb; David A Wood Journal: JACC Cardiovasc Interv Date: 2022-03-28 Impact factor: 11.195