PMID- 30978556 OWN - NLM STAT- MEDLINE DCOM- 20200130 LR - 20220323 IS - 1097-6744 (Electronic) IS - 0002-8703 (Linking) VI - 212 DP - 2019 Jun TI - Rationale and design of the randomized, controlled Early Valve Replacement Guided by Biomarkers of Left Ventricular Decompensation in Asymptomatic Patients with Severe Aortic Stenosis (EVOLVED) trial. PG - 91-100 LID - S0002-8703(19)30054-7 [pii] LID - 10.1016/j.ahj.2019.02.018 [doi] AB - BACKGROUND: The optimal timing of aortic valve replacement in asymptomatic patients with aortic stenosis is uncertain. Replacement fibrosis, as assessed by midwall (nonischemic) late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging, is an irreversible marker of left ventricular decompensation in aortic stenosis. Once established, it progresses rapidly and is associated with poor long-term prognosis in a dose-dependent manner. TRIAL DESIGN: The objective of this multicenter prospective randomized controlled trial is to determine whether early aortic valve replacement in asymptomatic patients with severe aortic stenosis can improve the adverse prognosis associated with midwall LGE. Patients will be screened for likelihood of having LGE with electrocardiography or high-sensitivity troponin I. Those at high risk will proceed to CMR imaging. Approximately 400 patients with midwall LGE will be randomized 1:1 to early valve replacement or routine care. Those who do not exhibit midwall LGE will continue with routine care and be randomized to a study registry or no further follow-up. Follow-up will be annual for approximately 3 years until the number of required outcome events is achieved. The primary endpoint is a composite of all-cause mortality and unplanned aortic stenosis-related hospitalization. The expected event rate is 25.0% in the routine care arm and 13.4% in the early intervention arm over the first 2 years; 88 observed primary outcome events will give 90% power at 5% significance level. Key secondary endpoints include all-cause mortality, sudden cardiac death, stroke, and symptomatic status. CONCLUSION: The EVOLVED trial is the first multicenter randomized controlled trial to compare early aortic valve replacement to routine care in asymptomatic patients with severe aortic stenosis and midwall LGE. CI - Copyright (c) 2019 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Bing, Rong AU - Bing R AD - British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. FAU - Everett, Russell J AU - Everett RJ AD - British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. FAU - Tuck, Christopher AU - Tuck C AD - Edinburgh Clinical Trials Unit, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK. FAU - Semple, Scott AU - Semple S AD - British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. FAU - Lewis, Steff AU - Lewis S AD - Edinburgh Clinical Trials Unit, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK. FAU - Harkess, Ronnie AU - Harkess R AD - Edinburgh Clinical Trials Unit, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK. FAU - Mills, Nicholas L AU - Mills NL AD - British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. FAU - Treibel, Thomas A AU - Treibel TA AD - Barts Health NHS Trust and University College London, London, United Kingdom. FAU - Prasad, Sanjay AU - Prasad S AD - Imperial College London and Royal Brompton Hospital, London, United Kingdom. FAU - Greenwood, John P AU - Greenwood JP AD - Leeds Institute for Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom. FAU - McCann, Gerry P AU - McCann GP AD - Department of Cardiovascular Sciences, University of Leicester, and the NIHR Leicester Biomedical Research Centre, Leicester, United Kingdom. FAU - Newby, David E AU - Newby DE AD - British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. FAU - Dweck, Marc R AU - Dweck MR AD - British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom. Electronic address: Marc.dweck@ed.ac.uk. LA - eng SI - ClinicalTrials.gov/NCT03094143 GR - FS/14/78/31020/BHF_/British Heart Foundation/United Kingdom GR - CH/09/002/26360/BHF_/British Heart Foundation/United Kingdom GR - U01 HL123336/HL/NHLBI NIH HHS/United States GR - FS/16/14/32023/BHF_/British Heart Foundation/United Kingdom GR - U01 HL123339/HL/NHLBI NIH HHS/United States GR - G0701127/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190315 PL - United States TA - Am Heart J JT - American heart journal JID - 0370465 SB - IM MH - Aged MH - Aortic Valve/*diagnostic imaging/surgery MH - Aortic Valve Stenosis/complications/*diagnosis/surgery MH - Asymptomatic Diseases MH - Echocardiography MH - Electrocardiography MH - Female MH - Follow-Up Studies MH - Heart Valve Prosthesis Implantation/*methods MH - Humans MH - Hypertrophy, Left Ventricular/*diagnosis/etiology/physiopathology MH - Magnetic Resonance Imaging, Cine/*methods MH - Male MH - Middle Aged MH - Myocardium/*pathology MH - Prognosis MH - Prospective Studies MH - Severity of Illness Index MH - Ventricular Function, Left/*physiology EDAT- 2019/04/13 06:00 MHDA- 2020/01/31 06:00 CRDT- 2019/04/13 06:00 PHST- 2018/09/28 00:00 [received] PHST- 2019/02/15 00:00 [accepted] PHST- 2019/04/13 06:00 [pubmed] PHST- 2020/01/31 06:00 [medline] PHST- 2019/04/13 06:00 [entrez] AID - S0002-8703(19)30054-7 [pii] AID - 10.1016/j.ahj.2019.02.018 [doi] PST - ppublish SO - Am Heart J. 2019 Jun;212:91-100. doi: 10.1016/j.ahj.2019.02.018. Epub 2019 Mar 15.