Myocardial Fibrosis and Early Intervention in Asymptomatic Patients With Severe Aortic Stenosis

Importance: Myocardial fibrosis burden has been associated with adverse clinical outcomes in symptomatic patients with aortic stenosis. Objective: To determine whether midwall myocardial fibrosis burden is associated with adverse clinical outcomes in asymptomatic patients and whether those with more fibrosis derive greater benefit from early intervention. Design, Setting, and Participants: This post hoc analysis of a randomized clinical trial was conducted between August 2017 and October 2022. The trial took place at 24 cardiac centers across the United Kingdom and Australia. Participants included asymptomatic patients with severe aortic stenosis and midwall fibrosis on cardiac magnetic resonance. These data were analyzed from October 2024 through June 2025. Intervention: Early intervention with transcatheter or surgical aortic valve replacement. Main Outcomes and Measures: Primary outcome was all-cause death or unplanned aortic stenosis-related hospitalization. Secondary outcomes included the individual components of the primary outcome. Results: In 224 trial participants (mean [SD] age, 73 [9] years; 63 women and 161 men, and mean [SD] aortic valve peak velocity 4.3 [0.5] m per second) with a median follow-up of 42 months, fibrosis burden (per 1% increase) was associated with an increase in the primary end point (hazard ratio [HR], 1.23; 95% CI, 1.08-1.37) and its component of unplanned aortic stenosis-related hospitalizations (HR, 1.22; 95% CI, 1.03-1.40) but not all-cause death (HR, 1.17; 95% CI, 0.98-1.35). There were no interactions between randomization arm and the midwall fibrosis burden for the primary (P for interaction = .39) or secondary end points. In patients with high fibrosis burden above the median, the primary end point occurred in 12 of 59 (20%) of those randomized to early intervention and 17 of 53 (32%) of those randomized to guideline-directed conservative management (HR, 0.62; 95% CI, 0.29-1.28). For the individual components, all-cause death occurred in 9 (15%) and 10 (19%) patients, respectively (HR, 0.84; 95% CI, 0.33-2.07), and unplanned aortic stenosis-related hospitalization in 4 (7%) and 13 (25%) patients respectively (HR, 0.27; 95% CI, 0.08-0.77). In patients with low fibrosis burden below the median, there were no differences in the primary outcome (HR, 1.05; 95% CI, 0.39-2.86) or its components between intervention groups. Conclusions and Relevance: In this study, in asymptomatic patients with severe aortic stenosis, higher midwall fibrosis burden was associated with adverse outcomes. There was no demonstrable heterogeneity by the degree of midwall fibrosis for the treatment effects of early surgical or transcatheter aortic valve replacement compared to clinical surveillance. Trial Registration: ClinicalTrials.gov Identifier: NCT03094143.

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Journal
JAMA Cardiology
Published
2026-04-15
DOI
https://doi.org/10.1001/jamacardio.2026.0654
Primary Topic
Cardiac Valve Diseases and Treatments
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article
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article

Myocardial Fibrosis and Early Intervention in Asymptomatic Patients With Severe Aortic Stenosis

Su Ern Yeoh, Vijay Kunadian, Rong Bing, Gracie Maloney et al.
JAMA Cardiology
Cardiac Valve Diseases and Treatments
article

Myocardial Fibrosis and Early Intervention in Asymptomatic Patients With Severe Aortic Stenosis

Su Ern Yeoh, Vijay Kunadian, Rong Bing, Gracie Maloney, Emily Redman, Suzanne Higson, Mervyn Andiapen, N. Boon, Denise O'Donell, Krithika Loganath, Madelaine Ocampo, Anvesha Singh, Vasiliki Tsampasian, Martin Sherwood, Nicholas L. Mills, Laura Gallego, Thabitha Charles, Melanie Tolson, April Edwards, Rachael Campbell, Jonaifah Ramirez, Amanda Solesbury, Jonathan Breeze, Saadia Aslam, Anu Oommen, Gillian Donaldson, Amy Raynsford, Steven Church, Dan Sado, Manish Motwani, Fiona Hall, Christopher Tuck, Abigail Knighton, Sheetal Crasta, Lucinda Wynne, Lauren Kittridge, Jason N. Dungu, Chiara Bucciarelli‐Ducci, Michail Sionas, Sujata Blane, Johannes Pintacasi, Akhila Muthuswamy, Nikhil V. Joshi, Sarah Mackie, David P. Ripley, Jodie Hussain, Preetha Mathew, Phillip Rayson, Joanne Crowe, Kelly Patel, C Y Chin, Sofia Matia, Annaliza Sevilliano, Jovita Rebong, Jacqueline Colnet, Victoria Clegg, Rajeev Padjama, Anne Ankers, Philip McGrouther, Timothy Fairbairn, R P Steeds, C C Lang, V Vassiliou, S J Leslie, Dana Dawson, Colin Berry, Kush Patel, Tariq Ramtoola, Sanjay K. Prasad, Simona Botezatu, Dani Cooke, Sandeep S. Hothi, Niall G. Keenan, Adele Trueman, Stephanie Hunt, Anita McNab, James Morrissey, Neil J. Craig, Patrycja Molek, Anne Scott, EVOLVED investigators, Gerry P. McCann, Dean Miller, Jonathan Byrne, Hunaid Vohra, Marc R. Dweck, Russell J. Everett, Bernard Prendergast, Ronak Rajani, Patrick A. Calvert, Tom MacGillivray, Maju Jose, Thomas A. Treibel, Aoife Tipping, John P. Greenwood, Stephen Dorman, Christopher A. Miller, David E. Newby, Graham S. Hillis, Kathryn Walker
article en

Abstract

Importance: Myocardial fibrosis burden has been associated with adverse clinical outcomes in symptomatic patients with aortic stenosis. Objective: To determine whether midwall myocardial fibrosis burden is associated with adverse clinical outcomes in asymptomatic patients and whether those with more fibrosis derive greater benefit from early intervention. Design, Setting, and Participants: This post hoc analysis of a randomized clinical trial was conducted between August 2017 and October 2022. The trial took place at 24 cardiac centers across the United Kingdom and Australia. Participants included asymptomatic patients with severe aortic stenosis and midwall fibrosis on cardiac magnetic resonance. These data were analyzed from October 2024 through June 2025. Intervention: Early intervention with transcatheter or surgical aortic valve replacement. Main Outcomes and Measures: Primary outcome was all-cause death or unplanned aortic stenosis-related hospitalization. Secondary outcomes included the individual components of the primary outcome. Results: In 224 trial participants (mean [SD] age, 73 [9] years; 63 women and 161 men, and mean [SD] aortic valve peak velocity 4.3 [0.5] m per second) with a median follow-up of 42 months, fibrosis burden (per 1% increase) was associated with an increase in the primary end point (hazard ratio [HR], 1.23; 95% CI, 1.08-1.37) and its component of unplanned aortic stenosis-related hospitalizations (HR, 1.22; 95% CI, 1.03-1.40) but not all-cause death (HR, 1.17; 95% CI, 0.98-1.35). There were no interactions between randomization arm and the midwall fibrosis burden for the primary (P for interaction = .39) or secondary end points. In patients with high fibrosis burden above the median, the primary end point occurred in 12 of 59 (20%) of those randomized to early intervention and 17 of 53 (32%) of those randomized to guideline-directed conservative management (HR, 0.62; 95% CI, 0.29-1.28). For the individual components, all-cause death occurred in 9 (15%) and 10 (19%) patients, respectively (HR, 0.84; 95% CI, 0.33-2.07), and unplanned aortic stenosis-related hospitalization in 4 (7%) and 13 (25%) patients respectively (HR, 0.27; 95% CI, 0.08-0.77). In patients with low fibrosis burden below the median, there were no differences in the primary outcome (HR, 1.05; 95% CI, 0.39-2.86) or its components between intervention groups. Conclusions and Relevance: In this study, in asymptomatic patients with severe aortic stenosis, higher midwall fibrosis burden was associated with adverse outcomes. There was no demonstrable heterogeneity by the degree of midwall fibrosis for the treatment effects of early surgical or transcatheter aortic valve replacement compared to clinical surveillance. Trial Registration: ClinicalTrials.gov Identifier: NCT03094143.

JAMA Cardiology
University of East Anglia (GB), Jagiellonian University (PL), St Bartholomew's Hospital (GB), University Hospitals Birmingham NHS Foundation Trust (GB), St Thomas' Hospital (GB), University of Hertfordshire (GB), Baker Heart and Diabetes Institute (AU), University of Liverpool (GB), University of Leicester (GB), University of Dundee (GB), The University of Western Australia (AU), University of Aberdeen (GB), Guy's and St Thomas' NHS Foundation Trust (GB), Barts Health NHS Trust (GB), Queen Elizabeth Hospital Birmingham (GB), Leeds Teaching Hospitals NHS Trust (GB), Norfolk and Norwich University Hospital (GB), Manchester Academic Health Science Centre (GB), Royal Perth Hospital (AU), West Hertfordshire Hospitals NHS Trust (GB), University Hospitals Bristol NHS Foundation Trust (GB), Northumbria Healthcare NHS Foundation Trust (GB), Raigmore Hospital (GB), Newcastle upon Tyne Hospitals NHS Foundation Trust (GB), Freeman Hospital (GB), Manchester Royal Infirmary (GB), Glenfield Hospital (GB), Harefield Hospital (GB), Edinburgh Royal Infirmary (GB), University of Manchester (GB), British Heart Foundation (GB), Liverpool Heart and Chest Hospital (GB), Manchester University NHS Foundation Trust (GB), Papworth Hospital NHS Foundation Trust (GB), Essex Cardiothoracic Centre (GB), National Heart Centre Singapore (SG), Cleveland Clinic London (GB), Evolved Analytics (United States) (US), Corona (Poland) (PL), The Royal Wolverhampton NHS Trust (GB), NIHR Leicester Biomedical Research Centre (GB), University College London (GB), Imperial College London (GB), Anglia Ruskin University (GB), University of Glasgow (GB), University of Birmingham (GB), National University of Malaysia (MY), University of Edinburgh (GB)
British Heart Foundation, Medical Research Council
Good health and well-being
Openalex Percentile: Top 29%
Cardiac Valve Diseases and Treatments
DOIOpen Access PDFOpenAlex
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