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Multicenter Study
. 2025 May 1;10(5):446-455.
doi: 10.1001/jamacardio.2024.5593.

Sex-Specific Association of Myocardial Fibrosis With Mortality in Patients With Aortic Stenosis

Soongu Kwak  1 , Anvesha Singh  2 , Russell J Everett  3 , Thomas A Treibel  4 , Jaehyun Lim  1 , Sungho Won  5 , Michelle C Williams  3 , Krithika Loganathan  3 , Rong Bing  3 , Neil Craig  3 , Trisha Singh  3 , Shruti Joshi  3 , Heesun Lee  1 , Whal Lee  6 , Yong-Jin Kim  1   7 , Calvin W L Chin  8 , Miho Fukui  9 , Tarique Al Musa  10 , Marzia Rigolli  11 , Lionel Tastet  12 , Laura E Dobson  10 , Stephanie Wiesemann  13 , Vanessa M Ferreira  11 , Gabriella Captur  14 , Sahmin Lee  15 , Jeanette Schulz-Menger  13 , Erik B Schelbert  16 , Marie-Annick Clavel  12 , Sung-Ji Park  17 , Costanza Pellegrini  18 , Martin Hadamitzky  19 , Bernhard L Gerber  20 , David E Newby  3 , Saul G Myerson  11 , Phillipe Pibarot  12 , João L Cavalcante  9   16 , Gerry P McCann  2 , John P Greenwood  10 , James C Moon  4 , Marc R Dweck  3 , Seung-Pyo Lee  1   7   21
Affiliations
Multicenter Study

Sex-Specific Association of Myocardial Fibrosis With Mortality in Patients With Aortic Stenosis

Soongu Kwak et al. JAMA Cardiol. .

Abstract

Importance: Myocardial fibrosis in aortic stenosis (AS) may exhibit sex differences. However, its prognostic significance in women with AS remains unclear.

Objective: To investigate sex differences in myocardial fibrosis assessed by cardiovascular magnetic resonance (CMR) and evaluate its prognostic value in women and men with AS.

Design, setting, and participants: Patients with severe AS who underwent CMR before aortic valve replacement (AVR) were prospectively enrolled from 13 international sites between March 2011 and September 2021. Myocardial fibrosis was evaluated using extracellular volume fraction (ECV%) and late gadolinium enhancement (LGE). The main analysis was conducted on patients without obstructive coronary artery disease (CAD), defined as those with no history of myocardial infarction and no concomitant coronary artery bypass grafting. Data were analyzed from December 2023 to February 2024.

Exposures: Surgical or transcatheter AVR.

Main outcomes and measures: The primary outcome was post-AVR all-cause mortality and the secondary outcome was cardiovascular mortality.

Results: Of 822 patients, 670 were without obstructive CAD (368 men [55%] and 302 women [45%]). Among these, women and men had a similar age (median, 72 years vs 71 years, respectively), comorbidities, and AS severity. ECV% was similar between sexes; however, women had less LGE (both infarct and noninfarct LGE). After a median follow-up of 3.7 (IQR, 2.1-4.7) years, there were 76 deaths (11.3%), including 29 adjudicated cardiovascular deaths, in patients without obstructive CAD. Increasing ECV% and LGE were associated with higher all-cause and cardiovascular mortality in both sexes. Cox analyses demonstrated that both ECV% and LGE were associated with higher all-cause mortality without significant interaction by sex (women: adjusted hazard ratio [HR], 1.08 per 1% ECV% increase; 95% CI, 1.04-1.12; P < .001; men: adjusted HR, 1.01; 95% CI, 0.96-1.06; P = .66; P for interaction by sex = .09 and women: adjusted HR, 2.49 for the presence of LGE; 95% CI, 1.07-5.80; P = .03; men: adjusted HR, 1.82; 95% CI, 1.00-3.32; P = .04; P for interaction by sex = .68). In the entire population (n = 822), both noninfarct and infarct-related LGE were associated with increased mortality without significant interaction by sex.

Conclusions and relevance: In this study, patients with severe AS who underwent AVR exhibited similar ECV% between sexes, while women had lower LGE. Increased myocardial fibrosis provided important prognostic value for both sexes.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Williams reported consultant fees from Canon, Feops, Novartis, and Siemens Healthineers outside the submitted work. Dr Fukui reported personal fees from Anteris Technologies and Edwards Lifescience outside the submitted work. Dr Rigolli reported employment from Bristol Myers Squibb outside the submitted work. Dr Ferreira reported salary from the University of Oxford from the British Heart Foundation during the conduct of the study and grants from GE Healthcare outside the submitted work; in addition, Dr Ferreira had a patent pending research license for WO/2020/161481 to GE Healthcare, a patent for WO/2021/044153 pending research license to GE Healthcare and a patent research license issued for US 11,747,426 B2 to GE Healthcare. Dr Schelbert reported personal fees from Haya Therapeutics outside the submitted work. Dr Clavel reported grants from Edwards Lifesciences, Medtronic, Pi-Cardia, Novartis, and Rednvia outside the submitted work. Dr Gerber reported personal fees from Bristol Myers Squibb and Novartis outside the submitted work. Dr Pibarot reported grants from Edwards Lifesciences Echo Corelab, Medtronic, Pi-Cardia, and Novartis outside the submitted work. Dr Cavalcante reported grants from Abbott Structural, Allina Health Foundation, JenaValve, the National Institutes of Health/National Heart, Lung, and Blood Institute, and honoraria or consultation fees from 4C Medical, Abbott Structural, Alleviant, Anteris, Boston Scientific, Circle Cardiovascular Imaging, Edwards Lifesciences, JenaValve, JC Medical, Medtronic, Novo Nordisk, Pie Medical, Siemens Healthineers, Shockwave, and Zoll outside the submitted work. Dr Moon reported stock holding from MyCardium outside the submitted work. No other disclosures were reported.

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