Early Intervention in Patients With Asymptomatic Severe Aortic Stenosis and Myocardial Fibrosis
Authors: Loganath Krithika , Craig Neil J. , Everett Russell J. , Bing Rong , Tsampasian Vasiliki , Molek Patrycja , Botezatu Simona , Aslam Saadia , Lewis Steff , Graham Catriona , White Audrey C. , MacGillivray Tom , Tuck Christopher E. , Rayson Phillip , Cranley Denise , Irvine Sian , Armstrong Ruth , Milne Lynsey , Chin Calvin W. L. , Hillis Graham S. , Fairbairn Timothy , Greenwood John P. , Steeds Richard , Leslie Stephen J. , Lang Chim C. , Bucciarelli-Ducci Chiara , Joshi Nikhil V. , Kunadian Vijay , Vassiliou Vassilios S. , Dungu Jason N. , Hothi Sandeep S. , Boon Nicholas , Prasad Sanjay K. , Keenan Niall G. , Dawson Dana , Treibel Thomas A. , Motwani Mani , Miller Christopher A. , Mills Nicholas L. , Rajani Ronak , Ripley David P. , McCann Gerry P. , Prendergast Bernard , Singh Anvesha , Newby David E. , Dweck Marc R. ,   EVOLVED investigators, Patel Kush , Andiapen Mervyn , Wynne Lucinda , Vohra Hunaid , Hussain Jodie , Patel Kelly , Dorman Stephen , Gallego Laura , Ramirez Jonaifah , Redman Emily , Matia Sofia , Ocampo Madelaine , Sevilliano Annaliza , Maloney Gracie , Solesbury Amanda , Church Steven , Kittridge Lauren , Rebong Jovita , Colnet Jacqueline , Pintacasi Johannes , Morrissey James , Tipping Aoife , Hunt Stephanie , Raynsford Amy , Cooke Dani , Sado Dan , Byrne Jonathan , Knighton Abigail , Breeze Jonathan , Sionas Michail , Crowe Joanne , Jose Maju , Charles Thabitha , Oommen Anu , Clegg Victoria , Edwards April , Trueman Adele , Padjama Rajeev , Higson Suzanne , Sherwood Martin , Mackie Sarah , McNab Anita , Mathew Preetha , Muthuswamy Akhila , Blane Sujata , Crasta Sheetal , Walker Kathryn , Ankers Anne , McGrouther Philip , Miller Dean , O'Donell Denise , Tolson Melanie , Scott Anne , Hall Fiona , Donaldson Gillian , Yeoh Su Ern , Campbell Rachael , McDonald Debbie , Patience Donna , Corballise Natasha , Moore Donna , Ilsley Mary , Matthews Iain , Runnett Craig , McCafferty Gemma , McKie Hayley , Campbell Helen , Calvert Patrick , Bullock Kat , Galloway Catherine , Gilbert Tom , Hillis Lorraine , Nikolaidis Nicolas , Cotton James , Rescigno Giuseppe , Radford Elizabeth , Thambyrajah Jeetendra , Maredia Neil , Ward Ben , Dale Rachel , Sharma Harish , Nilsson Annette , Brotherton Helen , Akramul Tabassuma , Hutton Kady , McDonald Sonia , Dykes Caroline , Timmins Vikki , Bubb Michael , Isaacs Karen , Mobley Alastair , Harries Valerie , Maclennan Beverley , Ali Kashan , Iskandar Zaid , Hussain Muhammad , Callaghan Marie , Glenwright Margaret , Nailon Hilary , Morrow Frank , Orr Karie , Murray Caitlin , Geddes Ailsa , Miyanza Prudence , Jeram Patricia , Deojee Danielle , Berry Colin , Joseph Anil , Sykes Robert , Brown Ammani , Fallon Kirsty , Doig Siouxsie , Kelly Laura , Hopkins Tracey , Dymock Laura , Woodward Rosie , Roditi Giles , Smith Kate , Gorecka Miroslawa , Roxas Anita , Bijsterveld Petra , Richards Fiona , Jude Rosemary , Newman Hannah , Grant Emma , Somers Kathryn , Aldridge Lucy , Wormleighton Joanne , Joseph Jincy , Zhao Xiaobei , Walker Elaine , Norris Lillian , L'Heureux Catherine , Lee Robert , Boyd Julia , Harkess Ronald , Mossop Helen , Masterton Nigel , Young Douglas 
Published: October 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