Cardiovascular Magnetic Resonance Highlights Sex-Specific Characteristics in Aortic Stenosis

Measuring myocardial fibrosis in male and female patients with more severe forms of aortic stenosis (AS) was a useful prognostic tool for each sex, according to new study results. Additionally, male and female patients had comparable extracellular volume fraction (ECV%), although women exhibited lower levels of late gadolinium enhancement (LGE). These findings were published in JAMA Cardiology in a new study investigating sex-specific differences in the AS population.1

Aortic Stenosis remains a serious, worldwide cardiovascular complication | image credit: Pumpala - stock.adobe.come

AS remains a serious cardiovascular complication that contributes to a great deal of morbidity and mortality around the world. As one’s aortic valve becomes too narrow and blood flow more restricted, left ventricle (LV) hypertrophy develops to maintain heart function; this condition progresses over time and increases individual risk of heart failure, resulting from greater degrees of myocardial fibrosis, myocyte death, and eventually more severe cardiac symptoms.2-4

Prior research has established ECV% and LGE as strong predictors of patient mortality in AS. Expanding on this, the present authors detail the growing interest in the utility of cardiovascular magnetic resonance (CMR) for assessing myocardial fibrosis and LV degeneration in patients with AS. Notably, they see the potential for these CMR evaluations to guide decisions about whether a patient needs an early aortic valve replacement (AVR).1

Yet, distinguishable characteristics related to individual sex remain poorly documented and defined. Research of this sort is necessary for evaluating the AS population, as the authors point to conflicting studies that suggest one of the sexes develops more myocardial fibrosis—or less—than the other. As such, an international, multicenter study was conducted to analyze these outcomes in a larger cohort of patients with AS who were going through CMR before AVR.

Patients were included throughout the US, Canada, UK, Belgium, Germany, and South Korea, featuring a total of 822 individuals. The cohort was 41.6 female (n = 342) and 58.4% male (n = 480). Body mass index, age, and severity of AS was similar in both groups, as was the presence of hypertension, diabetes, and atrial fibrillation. Female patients registered higher scores on the Society of Thoracic Surgeons Predicted Risk of Mortality (median of 1.8 vs 1.3; P < .001).

There were 670 patients who did not exhibit obstructive coronary artery disease (302 women vs 360 men).

The authors pointed out that there was minimal variation when it came to ECV% and LGE between the sexes, but women presented with lower ratios of LV mass index, LV wall thickness, and LV mass volume compared with men. Women also exhibited lesser LV volumes and greater LV ejection fractions than men, but LV stroke volume indices were similar.

Women also experienced superior overall survival rates vs men (32 deaths [9.4%] vs 71 deaths [14.8%]; P = .02). These instances were attributed to cardiovascular complications; the authors note that survival rates unrelated to cardiovascular mortality did not significantly vary.

Greater ECV% was linked with mortality for both sexes (women: adjusted HR, 1.08 per 1% increase in ECV%; 95% CI, 1.04-1.12; P < .001); men: adjusted HR, 1.01; 95% CI, 0.96-1.06; P = .66; P by interaction by sex = .09), as was LGE (women: adjusted HR, 2.49 by the presence of LGE; 95% CI, 1.07-5.8; P = .03; men: adjusted HR, 1.82; 95% CI, 1.0-3.32; P = .04; P by interaction by sex = .68).

“Our data highlight important sex differences in LV remodeling in AS and provide a notable advance in our understanding of how the ventricle starts to decompensate in men and women with AS,” the authors concluded. “In particular, we have demonstrated that women have more favorable patterns of remodeling and less replacement myocardial fibrosis than men while having similar degrees of ECV%,” they added, advocating for the potential benefits that CMR can provide for sex-based risk stratification in AS. 

References

1. Kwak S, Singh A, Everett RJ, et al. Sex-specific association of myocardial fibrosis with mortality in patient with aortic stenosis. JAMA Cardiol. Published online February 19, 2025. doi:10.1001/jamacardio.2024.5593

2. Coffey S, Roberts-Thomson R, Brown A, et al. Global epidemiology of valvular heart disease. Nat Rev Cardiol. 2021;18(12):853-864. doi:10.1038/s41569-021-00570-z

3. Bing R, Cavalcante JL, Everett RJ, Clavel MA, Newby DE, Dweck MR. Imaging and impact of myocardial fibrosis in aortic stenosis. JACC Cardiovasc Imaging. 2019;12(2):283-296. doi:10. 1016/j.jcmg.2018.11.026 3.

4. Dweck MR, Boon NA, Newby DE. Calcificaortic stenosis: a disease of the valve and the myocardium. J Am Coll Cardiol. 2012;60(19):18541863. doi:10.1016/j.jacc.2012.02.093