Older patients and women with chronic aortic regurgitation (AR) maintained smaller left ventricular (LV) volumes than younger patients and men, resulting in the development of adverse events (AE) at lower LV volumes, according to new research. In a single-center observational study, scientists found age and sex did significantly impact on the degree of LV remodeling and outcomes, increasing the urgency for age- and sex-specific LV volume thresholds to be considered. “The aging process is characterized by progressive myocyte loss and alteration in myocardial signaling at the subcellular level,” said the study, published Monday online and in the April 18 issue of the Journal of the American College of Cardiology. “These characteristic changes invariably lead to decreasing LV volume with age and a reduced ability of the LV to adapt to change in loading conditions. “With respect to sex differences, women generally have smaller LV volumes than men despite indexing to body surface area (BSA).” Current AR guidelines recommend surgery in asymptomatic patients with chronic AR in case of LV systolic dysfunction (LV ejection fraction <55%; Class I) and severe LV dilatation (LV end-systolic diameter >50 mm or >25 mm/mm2; Class IIa). Progressive decline in LV systolic function or progressive increase in LV diastolic dimensions falls into the severe range (LV end-diastolic dimeter >65 mm; Class IIb). Study approach Led by Emmanuel Akintoye, MD, from the Cleveland Clinic, the team enrolled 525 adult patients (26% women), following up with an echocardiogram at a median of 2 years (interquartile range [IQR]: 1.0-3.6 years). These patients had moderate to severe AR or severe AR and LV ejection fraction ≥50% and were serially monitored by echocardiogram between 2010 and 2016 at the Cleveland Clinic. One of the two main endpoints were LV end-systolic volume indexed to body surface area (LVESVi) and LV end-diastolic volume indexed to body surface area. The other endpoint was adverse event (AE) incidence, defined as a composite of mortality, incident heart failure hospitalization, or urgent aortic valve surgery (whichever occurred first). The research team evaluated the longitudinal rate of LV remodeling and determined the association between LV volume and AE by age and sex. Research findings Findings revealed that at baseline, older patients (age ≥60 years) had smaller LV volumes compared with younger patients (age <60 years). The mean LVESVi for older patients was 27.3 mL/m2 compared to a mean LVESVi of 32.3 mL/m2 for younger patients. Similarly, women had smaller LV volumes compared with men (mean LVESVi was 23.3 mL/m2 vs 32.4 mL/m2). On serial evaluation, older patients and women maintained smaller LV volumes compared with younger patients and men. Further findings revealed that there were 210 (40%) AE during follow-up. The optimal discriminatory threshold for AE varies by age and sex. The team found the LVESVi threshold was highest for young men (50 mL/m2), intermediate for older men (35 mL/m2), and lowest for women (27 mL/m2). “In the absence of symptoms or other Class I indications for surgery, treatment guidelines recommend the use of the same linear dimensions to inform intervention in all patients,” the study pointed out. “We showed that volumetric assessment is superior to linear dimensions for prognostication and that the optimal discriminatory volume threshold for prognostication varies by sex, and the effect of age was more evident among men only.” Multimodality imaging approach needed Anna Sannino, MD, PhD, from the Baylor Research Institute in Plano, Texas, and Federico Fortuni, MD, from the San Giovanni Battista Hospital in Foligno, Italy, called for a multimodality imaging approach to evaluate LV remodeling in AR, especially in women. “Given the heterogeneous and sex specific cardiac remodeling, the use of unspecific cutoff values might lead to important disparities in referral for aortic valve surgery caused by severe chronic AR between men and women, and this may justify different outcomes,” they said in an accompanying editorial. The editorial supported the study’s conclusions by referring to previous reports proposing an LV end-systolic volume index of 40 to 45 mL/m2 as the optimal volume threshold for intervention. “[The reports] support the concept that unique linear dimensions fail to account for the complex LV geometric change caused by remodeling, as well as for the sex- and age-related peculiarity of its development,” the authors add. Sources: 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. Sannino A, Fortuni F. Timing for Intervention in Aortic Regurgitation: When One Does Not Fit All. J Am Coll Cardiol. 2023;81:1488–1490 Image Credit: ibreakstock – stock.adobe.com