Age and Sexual Dimorphism in Aortic Regurgitation
By Michael H. Crawford, MD, Editor
SYNOPSIS: Among patients with chronic, significant aortic regurgitation, women and older men without symptoms indicating the need for aortic valve replacement maintained smaller left ventricular volumes than young men and developed adverse clinical events at lower left ventricular volumes.
SOURCE: Akintoye E, Saijo Y, Braghieri L, et al. Impact of age and sex on left ventricular remodeling in patients with aortic regurgitation. J Am Coll Cardiol 2023;81:1474-1487.
For humans with aortic regurgitation (AR), there is little known about how the left ventricle (LV) responds to the extra volume by age and sex. Investigators from the Cleveland Clinic sought to determine the effect of age and sex on the characteristics of the LV response to chronic AR over time.
From their echocardiographic database, Akintoye et al selected patients studied between 2010 and 2016 who were living with moderate to severe AR with an LV ejection fraction (EF) > 50%, a baseline, and at least one follow-up echo conducted more than six months from the first one. They excluded patients with significant other diseases of the left-sided valves, those who had undergone aortic valve (AV) surgery already, and those living with congenital heart disease (other than that of the AV). The authors focused on 525 eligible patients (mean age was 56 years; 26% were women) and followed them for a median of two years.
Three-quarters were asymptomatic, and the rest reported minimal symptoms (not considered enough to intervene on the AV). Bicuspid valves were present in 27%. Patients older than age 60 years exhibited significantly smaller body surface areas (BSA) and smaller LV end-systolic volume indices (ESVi; 27 mL/m2 vs. 32 mL/m2). Women recorded smaller LVESVi than men (23 mL/m2 vs. 32 mL/m2).
Adverse clinical events (ACE) occurred in 40% of patients: urgent AV replacement (AVR) in 26%, hospitalization for heart failure in 18%, and mortality in 8%. The ESVi associated with a significant increase in ACE was 27 mL/m2 for women and did not differ significantly by age. In men, there was a difference by age. The cutpoint was 35 mL/m2 for men older than age 60 years and 50 mL/m2 for men younger than age 60 years.
LV end-diastolic volume index (EDVi) also declined with aging, especially in men. The cutpoints for LVEDVi measurements were 69 mL/m2 for women, 75 mL/m2 for men older than age 60 years, and 94 mL/m2 for men younger than age 60 years. Both volume measures were superior at predicting ACE than linear measurements of LV diameters. The authors concluded that in patients with chronic, significant AR, women and older men without symptoms indicating the need for AVR maintained smaller LV volumes than did young men and experienced ACEs at lower LV volumes.
This is a critical paper. Akintoye et al confirmed there is a difference in the response of the LV to volume load depending on sex and age that persists over time. Specifically, the volumes at which ACE start to increase significantly are different in older men and women. Also, using linear diameter measurements on echo are not as accurate at determining the point at which ACEs begin to increase. Thus, these investigators suggested future guideline authors should take these differences in volumes into consideration and discourage the use of linear measurements by echo for decision-making. This information is important because older patients and women with these characteristics die more often than men. Akintoye et al reported a mortality rate of 14% for those older than age 60 years vs. 3.5% for those younger than age 60 years. Overall, the mortality rate for women was 12.6% vs. 6.9% for men. The authors suggested this may be at least partly because they used currently recommended cutpoints for surgical AVR (SAVR), which would be achieved much later in the course of chronic AR in women and older men.
There were limitations to the Akintoye et al study that must be considered before using their data for clinical decision-making. This was a single-center, retrospective study, so there might be biases and unmeasured confounders. Also, the echo time points were not consistent between patients. In addition, the authors included patients with multiple etiologies of AR, including those with aortic root dilatation. Finally, echo compared to MRI underestimates LV volumes, especially in women. As the cost and availability of cardiac MRI improves, this may be the better method for following patients with chronic AR. The bottomline is we will need a study using smaller-volume cutpoints for women and older men to prove outcomes are better before adopting the new numbers. In the meantime, it would be reasonable to consider the Akintoye et al study when you are on the fence about referring a woman or older man for SAVR.
Among patients with chronic, significant aortic regurgitation, women and older men without symptoms indicating the need for aortic valve replacement maintained smaller left ventricular volumes than young men and developed adverse clinical events at lower left ventricular volumes.
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