Myocardial Fibrosis and Early Intervention in Asymptomatic Patients With Severe Aortic Stenosis
Year: 2026
Type: article
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.
Source: JAMA Cardiology
Authors: Neil J. Craig, Krithika Loganath, Russell J. Everett, Rong Bing, Tariq Ramtoola, Vasiliki Tsampasian, Patrycja Molek, Simona Botezatu, Saadia Aslam, Tom MacGillivray, Christopher E. Tuck, Phillip Rayson, Patrick A. Calvert, Colin Berry, Calvin W.L. Chin, Graham S. Hillis, Timothy Fairbairn, John P. Greenwood, Richard Steeds, Stephen J. Leslie, Chim C. Lang, Chiara Bucciarelli-Ducci, Nikhil V. Joshi, Vijay Kunadian, Bernard Prendergast, Nicholas L. Mills, Vassilios S. Vassiliou, Jason N. Dungu, Sandeep S. Hothi, Nicholas Boon, Sanjay K. Prasad, Niall G. Keenan, Dana Dawson, Manish Motwani, Christopher A. Miller, Ronak Rajani, David P. Ripley, Thomas A. Treibel, Gerry P. McCann, Anvesha Singh, David E. Newby, Marc R. Dweck, EVOLVED investigators, Kush Patel, Mervyn Andiapen, Lucinda Wynne, Hunaid Vohra, Jodie Hussain, Kelly Patel, Stephen Dorman, Laura Gallego, Jonaifah Ramirez, Emily Redman, Sofia Matia, Madelaine Ocampo, Annaliza Sevilliano, Gracie Maloney, Amanda Solesbury, Steven Church, Lauren Kittridge, Jovita Rebong, Jacqueline Colnet, Johannes Pintacasi, James Morrissey, Aoife Tipping, Stephanie Hunt, Amy Raynsford, Dani Cooke, Dan Sado, Jonathan Byrne, Abigail Knighton, Jonathan Breeze, Michail Sionas, Joanne Crowe, Maju Jose, Thabitha Charles, Anu Oommen, Victoria Clegg, April Edwards, Adele Trueman, Rajeev Padjama, Suzanne Higson, Martin Sherwood, Sarah Mackie, Anita McNab, Preetha Mathew, Akhila Muthuswamy, Sujata Blane, Sheetal Crasta, Kathryn Walker, Anne Ankers, Philip McGrouther, Dean Miller, Denise O'Donell, Melanie Tolson, Anne Scott, Fiona Hall, Gillian Donaldson, Su Ern Yeoh, Rachael Campbell, Debbie McDonald, Donna Patience, Natasha Corballise, Donna Moore, Mary Ilsley, Iain Matthews, Craig Runnett, Gemma McCafferty, Hayley McKie, Helen Campbell, Kat Bullock, Catherine Galloway, Tom Gilbert, Lorraine Hillis, Nicolas Nikolaidis, James Cotton, Giuseppe Rescigno, Elizabeth Radford, Jeetendra Thambyrajah, Neil Maredia, Ben Ward, Rachel Dale, Harish Sharma, Annette Nilsson, Helen Brotherton, Tabassuma Akramul, Kady Hutton, Sonia McDonald, Caroline Dykes, Vikki Timmins, Michael Bubb, Karen Isaacs, Alastair Mobley, Valerie Harries, Beverley Maclennan, Kashan Ali, Zaid Iskandar, Muhammad Hussain, Marie Callaghan, Margaret Glenwright, Hilary Nailon, Frank Morrow, Karie Orr, Caitlin Murray, Ailsa Geddes, Prudence Miyanza, Patricia Jeram, Danielle Deojee, Anil Joseph, Robert Sykes, Ammani Brown, Kirsty Fallon, Siouxsie Doig, Laura Kelly, Tracey Hopkins, Laura Dymock, Rosie Woodward, Giles Roditi, Kate Smith, Miroslawa Gorecka, Anita Roxas, Petra Bijsterveld, Fiona Richards, Rosemary Jude, Hannah Newman, Emma Grant, Kathryn Somers, Lucy Aldridge, Joanne Wormleighton, Jincy Joseph, Xiaobei Zhao, Elaine Walker, Lillian Norris, Catherine L'Heureux, Robert Lee, Julia Boyd, Ronald Harkess, Helen Mossop, Nigel Masterton, Douglas Young
Institutions: Edinburgh Royal Infirmary, British Heart Foundation, University of Edinburgh, University of East Anglia, Norfolk and Norwich University Hospital, Jagiellonian University, Carol Davila University of Medicine and Pharmacy, University of Leicester, Glenfield Hospital, NIHR Leicester Biomedical Research Centre, University of Cambridge, Papworth Hospital NHS Foundation Trust, University of Glasgow, Royal Perth Hospital, National Heart Centre Singapore, Baker Heart and Diabetes Institute, The University of Western Australia, Liverpool Heart and Chest Hospital, Leeds Teaching Hospitals NHS Trust, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Raigmore Hospital, University of Dundee, National University of Malaysia, Guy's and St Thomas' NHS Foundation Trust, University Hospitals Bristol NHS Foundation Trust, Harefield Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle University, St Thomas' Hospital, Cleveland Clinic London, Essex Cardiothoracic Centre, Anglia Ruskin University, The Royal Wolverhampton NHS Trust, University of Birmingham, West Hertfordshire Hospitals NHS Trust, Imperial College London, University of Aberdeen, Manchester Royal Infirmary, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, University of Manchester, Northumbria Healthcare NHS Foundation Trust, St Bartholomew's Hospital, Barts Health NHS Trust, University College London
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7154469855