Sex-specific left ventricular (LV) dilatation cutoffs are needed to improve risk stratification in patients with moderate-severe aortic regurgitation (AR), a new study suggests. Pilar Lopez Sanit, MD, from the Leiden University Medical Center, the Netherlands, and colleagues, reported the corresponding data in a manuscript published online Wednesday in JAMA Cardiology. LV dilatation is used to predict adverse outcomes in patients with AR. Guidelines currently recommend aortic valve surgery (AVS) for patients with moderate to severe AR, and clinicians use the LV end-systolic diameter index (LVESDi) to indicate the threshold for treatment. The guidelines presently states that the thresholds are the same regardless of patient sex. LVES volume index (LVESVi) may be better for categorizing LV remodeling, but this measurement is only recommended in European guidelines. The European guidelines also have the same thresholds for both men and women. Investigators in this multicenter cohort study collected data from patients across five centers in the Netherlands, Singapore, Hong Kong, Canada and Romania between December 2003 and December 2022, and data were analyzed between January and November 2024. Follow-up time had a median of 7 years. Patients met inclusion criteria if they had moderate-severe AR and preserved LV ejection fraction (LVEF) (≥50%). If patients had symptoms, acute AR, other valvular disease or prior heart surgery, they were excluded from the study. The primary outcome in this study was all-cause death during treatment after AVS. Of the 808 patients (mean age=56 years; n=488 men, n=320 women; 78% White, 22% Asian) in the study, 323 had AVS. The mean baseline LVESDi was the similar across sexes (women=20 mm/m2, men=20 mm/m2; p=0.77), but men had significantly higher mean LVESVi (men=39 mL/m2, women=31 mL/m2; p<0.001). All-cause mortality occurred in 74 patients during medical management after surgery, and women had lower rates of 6-year survival (80%) compared with men (86%) (p=0.001). In both men and women, LVESDi was found to be 20 mm/m2, while the LVESVi threshold for mortality was 40 mL/m2 for women and 45 mL/m2 for men. The differences in outcomes remained even after multivariable adjustment, demonstrating significant differences in LVESVi thresholds for men versus women, but not in LVESDi thresholds. Survival rates were similar across sexes after AVS (women=85%, men=89%; p=0.31). Preoperative LVESVi levels showed differences in death rates. Sex interactions were significant (hazard ratio [HR]=1.03, 95% confidence interval [CI]=1.00-1.06, p=0.04). The retrospective design of this study was one limitation, in addition to lack of specific indications for AVS for all patients, though heart teams and guidelines were used for diagnosis criteria. Echocardiograms were also assessed by individual sites instead of an independent core laboratory. This study demonstrated that, in patients with moderate-to-severe AR, women and men have different LVESVi thresholds, predictive of mortality. Specific LVESVi cutoffs, namely 40 mL/m2 for women and 45 mL/m2 for men, may be used to improve risk stratification in AR management. Robert O. Bonow, MD, MS, from the Northwestern University Feinberg School of Medicine, Chicago, and Patrick T. O’Gara, MD, of the Brigham and Women’s Hospital, Boston, wrote an accompanying editor’s note about the treatment recommendations for patients with AR and the impacts of this present study on the AR patient population. “The current analysis by Lopez Santi et al adds novel findings regarding the preoperative values of LVESVi associated with postoperative outcome that differ between women and men,” Drs. Bonow and O’Gara wrote. “Importantly, these data also identify the importance of sex-based analyses of LV remodeling and emphasize that even after adjustment for body surface area, risk thresholds for LVESVi may need to be lowered in women compared with men.” Sources: Santi PL, Fortuni F, Bernard J, et al. Sex differences in left ventricular remodeling for risk stratification of patients with aortic regurgitation. JAMA Cardiol. 2026 January 21 (Article in Press). Bonow RO, O’Gara PT. Women’s Health: Sex differences in left ventricular remodeling and outcomes in aortic regurgitation. JAMA Cardiol. 2026 January 21 (Article in Press). Image Credit: Studio Romantic – stock.adobe.com