Heart Fibrosis Linked to Mortality in Aortic Stenosis: Does Sex Matter? Study Sheds Light

The findings, published in JAMA Cardiology, suggest that while men and women exhibit comparable extracellular volume fraction (ECV%), women tend to have lower levels of late gadolinium enhancement (LGE), a marker of focal myocardial fibrosis. Importantly, the study emphasizes the prognostic significance of increased myocardial fibrosis in both sexes.

Aortic stenosis leads to significant morbidity and mortality, with chronic pressure overload causing left ventricular hypertrophy, which eventually decompensates due to myocyte death and fibrosis. Cardiovascular magnetic resonance (CMR) enables noninvasive fibrosis assessment using late gadolinium enhancement and extracellular volume fraction. Sex-related differences in AS fibrosis remain unclear, necessitating further research.

Against the above background, Soongu Kwak, Department of Internal Medicine, Seoul National University Hospital, Seoul, South Korea, and colleagues aimed to examine sex-based variations in myocardial fibrosis detected through CMR and assess its prognostic significance in men and women with AS.

For this purpose, the researchers prospectively enrolled patients with severe AS from 13 international sites between 2011 and 2021, assessing myocardial fibrosis using ECV% and late gadolinium enhancement before aortic valve replacement. The analysis focused on patients without obstructive coronary artery disease, excluding those with a history of myocardial infarction or prior coronary artery bypass grafting. With data analyzed between December 2023 and February 2024, the study evaluated post-AVR all-cause mortality as the primary outcome and cardiovascular mortality as the secondary outcome.

The study led to the following findings:

• The study included 822 patients, of whom 670 did not have obstructive coronary artery disease (CAD), with 368 men (55%) and 302 women (45%).
• Women and men had similar median ages (72 versus 71 years), comparable comorbidities, and similar AS severity.
• ECV% was comparable between sexes, but women had lower levels of infarct and noninfarct LGE.
• After a median follow-up of 3.7 years, 11.3% of patients died, including 29 cardiovascular deaths.
• Higher ECV% and LGE were linked to increased all-cause and cardiovascular mortality in both sexes.
• Cox analysis showed ECV% was associated with higher all-cause mortality in women (adjusted HR, 1.08 per 1% increase) but not in men (adjusted HR, 1.01).
• The presence of LGE was associated with higher all-cause mortality in both women (adjusted HR, 2.49) and men (adjusted HR, 1.82), without significant sex interaction.
• In the full cohort (n=822), both infarct-related and noninfarct LGE were linked to increased mortality, with no significant sex-based differences.

"The findings showed that in patients with severe AS undergoing AVR, women exhibit less wall thickening, hypertrophy, and replacement myocardial fibrosis than men, despite having similar ECV%. Myocardial fibrosis remains a strong prognostic marker in both sexes, highlighting the value of noninvasive CMR-based fibrosis assessment for improved risk stratification and clinical decision-making in AS management," the researchers concluded.

Reference:

Kwak S, Singh A, Everett RJ, et al. Sex-Specific Association of Myocardial Fibrosis With Mortality in Patients With Aortic Stenosis. JAMA Cardiol. Published online February 19, 2025. doi:10.1001/jamacardio.2024.5593