Sex-Specific Association of Myocardial Fibrosis With Mortality in Patients With Aortic Stenosis
Authors: Soongu Kwak, Anvesha Singh, Russell J. Everett, Thomas A. Treibel, Jaehyun Lim, Sungho Won, Michelle C. Williams, Krithika Loganathan, Rong Bing, Neil Craig, Trisha Singh, Shruti Joshi, Heesun Lee, Whal Lee, Yong-Jin Kim, Calvin W. L. Chin, Miho Fukui, Tarique Al Musa, Marzia Rigolli, Lionel Tastet, Laura E. Dobson, Stephanie Wiesemann, Vanessa M. Ferreira, Gabriella Captur, Sahmin Lee, Jeanette Schulz-Menger, Erik B. Schelbert, Marie-Annick Clavel, Sung-Ji Park, Costanza Pellegrini, Martin Hadamitzky, Bernhard L. Gerber, David E. Newby, Saul G. Myerson, Phillipe Pibarot, João L. Cavalcante, Gerry P. McCann, John P. Greenwood, James C. Moon, Marc R. Dweck, Seung-Pyo Lee
Journal: JAMA Cardiology (2025)

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 &amp;amp;lt; .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.