Early Intervention in Patients With Asymptomatic Severe Aortic Stenosis and Myocardial Fibrosis
Authors: Krithika Loganath, Neil J. Craig, Russell J. Everett, Rong Bing, Vasiliki Tsampasian, Patrycja Molek, Simona Botezatu, Saadia Aslam, Steff Lewis, Catriona Graham, Audrey C. White, Tom MacGillivray, Christopher E. Tuck, Phillip Rayson, Denise Cranley, Sian Irvine, Ruth Armstrong, Lynsey Milne, 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, Vassilios S. Vassiliou, Jason N. Dungu, Sandeep S. Hothi, Nicholas Boon, Sanjay K. Prasad, Niall G. Keenan, Dana Dawson, Thomas A. Treibel, Mani Motwani, Christopher A. Miller, Nicholas L. Mills, Ronak Rajani, David P. Ripley, Gerry P. McCann, Bernard Prendergast, Anvesha Singh, David E. Newby, Marc R. Dweck, 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, Patrick Calvert, 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, Colin Berry, 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
Journal: JAMA (2024)

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