Early Intervention in Patients With Asymptomatic Severe Aortic Stenosis and Myocardial Fibrosis: The EVOLVED Randomized Clinical Trial

Loganath K 1 , Craig NJ 1 , Everett RJ 2 , Bing R 2 , Tsampasian V 3 , Molek P 4 Show all authors , Botezatu S 5 , Aslam S 6 , Lewis S 7 , Graham C 8 , White AC 1 , MacGillivray T 9 , Tuck CE 1 , Rayson P 7 , Cranley D 7 , Irvine S 7 , Armstrong R 7 , Milne L 7 , Chin CWL 10 , Hillis GS 11 , Fairbairn T 12 , Greenwood JP 13 , Steeds R 14 , Leslie SJ 15 , Lang CC 16 , Bucciarelli-Ducci C 17 , Joshi NV 17 , Kunadian V 18 , Vassiliou VS 3 , Dungu JN 19 , Hothi SS 20 , Boon N 21 , Prasad SK 22 , Keenan NG 23 , Dawson D 24 , Treibel TA 25 , Motwani M 26 , Miller CA 27 , Mills NL 1 , Rajani R 28 , Ripley DP 29 , McCann GP 6 , Prendergast B 30 , Singh A 6 , Newby DE 1 , Dweck MR 1 , EVOLVED investigators

Affiliations 

  • 1 British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, Scotland
  • 2 Edinburgh Heart Centre, Royal Infirmary of Edinburgh, Edinburgh, Scotland
  • 3 Norwich Medical School, University of East Anglia, Norwich, United Kingdom
  • 4 Department of Coronary Disease and Heart Failure, Jagiellonian University Medical College, Krakow, Poland
  • 5 University of Medicine and Pharmacy Carol Davila, Cardiology Department, Euroecholab, Bucharest, Romania
  • 6 Department of Cardiovascular Sciences, University of Leicester and the NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom
  • 7 Edinburgh Clinical Trials Unit, Usher Institute, The University of Edinburgh, Edinburgh, Scotland
  • 8 Edinburgh Clinical Research Facility, The University of Edinburgh, Edinburgh, Scotland
  • 9 Edinburgh Imaging, The University of Edinburgh, Edinburgh, Scotland
  • 10 Department of Cardiology, National Heart Centre Singapore, Singapore
  • 11 Medical School, University of Western Australia, Perth, Western Australia, Australia
  • 12 Department of Cardiology, Liverpool Centre for Cardiovascular Science, Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
  • 13 Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
  • 14 Department of Cardiology, Queen Elizabeth Hospital Birmingham, University Hospitals of Birmingham NHS Foundation Trust, Birmingham, United Kingdom
  • 15 Cardiac Unit, Raigmore Hospital, Inverness, Scotland
  • 16 Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, Scotland, United Kingdom
  • 17 Bristol Heart Institute, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom
  • 18 Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle, United Kingdom
  • 19 Essex Cardiothoracic Centre, Nethermayne, Basildon, Essex, United Kingdom
  • 20 Department of Cardiology, Royal Wolverhampton NHS Trust, Wolverhampton, UK, Institute of Cardiovascular Sciences, University of Birmingham, United Kingdom
  • 21 Retired, Hertfordshire, United Kingdom
  • 22 Royal Brompton and Harefield Hospitals, Guys' and St Thomas NHS Foundation Trust, London, United Kingdom
  • 23 Department of Cardiology, West Hertfordshire Hospitals NHS Trust, Watford, United Kingdom
  • 24 Aberdeen Cardiovascular and Diabetes Centre, University of Aberdeen, Aberdeen, Scotland
  • 25 Institute of Cardiovascular Sciences, University College London, and St Bartholomew's Hospital, Barts Health NHS Trust, West Smithfield, London, United Kingdom
  • 26 Department of Cardiology, Manchester Heart Institute, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester, United Kingdom
  • 27 Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom
  • 28 Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
  • 29 Cardiology, Northumbria Healthcare NHS Foundation Trust, Newcastle upon Tyne, United Kingdom
  • 30 Cleveland Clinic London and St Thomas' Hospital, London, United Kingdom
JAMA, 2025 Jan 21;333(3):213-221.
PMID: 39466640 DOI: 10.1001/jama.2024.22730

Abstract

IMPORTANCE: Development of myocardial fibrosis in patients with aortic stenosis precedes left ventricular decompensation and is associated with an adverse long-term prognosis.

OBJECTIVE: To investigate whether early valve intervention reduced the incidence of all-cause death or unplanned aortic stenosis-related hospitalization in asymptomatic patients with severe aortic stenosis and myocardial fibrosis.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, randomized, open-label, masked end point trial was conducted between August 2017 and October 2022 at 24 cardiac centers across the UK and Australia. Asymptomatic patients with severe aortic stenosis and myocardial fibrosis were included. The final date of follow-up was July 26, 2024.

INTERVENTION: Early valve intervention with transcatheter or surgical aortic valve replacement or guideline-directed conservative management.

MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of all-cause death or unplanned aortic stenosis-related hospitalization in a time-to-first-event intention-to-treat analysis. There were 9 secondary outcomes, including the components of the primary outcome and symptom status at 12 months.

RESULTS: The trial enrolled 224 eligible patients (mean [SD] age, 73 [9] years; 63 women [28%]; mean [SD] aortic valve peak velocity of 4.3 [0.5] m/s) of the originally planned sample size of 356 patients. The primary end point occurred in 20 of 113 patients (18%) in the early intervention group and 25 of 111 patients (23%) in the guideline-directed conservative management group (hazard ratio, 0.79 [95% CI, 0.44-1.43]; P = .44; between-group difference, -4.82% [95% CI, -15.31% to 5.66%]). Of 9 prespecified secondary end points, 7 showed no significant difference. All-cause death occurred in 16 of 113 patients (14%) in the early intervention group and 14 of 111 (13%) in the guideline-directed group (hazard ratio, 1.22 [95% CI, 0.59-2.51]) and unplanned aortic stenosis hospitalization occurred in 7 of 113 patients (6%) and 19 of 111 patients (17%), respectively (hazard ratio, 0.37 [95% CI, 0.16-0.88]). Early intervention was associated with a lower 12-month rate of New York Heart Association class II-IV symptoms than guideline-directed conservative management (21 [19.7%] vs 39 [37.9%]; odds ratio, 0.37 [95% CI, 0.20-0.70]).

CONCLUSIONS AND RELEVANCE: In asymptomatic patients with severe aortic stenosis and myocardial fibrosis, early aortic valve intervention had no demonstrable effect on all-cause death or unplanned aortic stenosis-related hospitalization. The trial had a wide 95% CI around the primary end point, with further research needed to confirm these findings.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03094143.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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