Revised Left Ventricular Remodeling Thresholds Predict Mortality in Asymptomatic Aortic Regurgitation: JAMA
Netherlands: A new cohort study published in JAMA has shown that existing thresholds for left ventricular remodeling may need revision to better predict mortality risk in patients with asymptomatic aortic regurgitation and preserved ejection fraction, indicating the importance of earlier and more refined risk stratification.
The study, led by Pilar Lopez Santi from the Department of Cardiology, Heart Lung Center, Leiden University Medical Center, Leiden, the Netherlands, and colleagues, examined whether sex-specific measures of left ventricular (LV) remodeling could improve prognostic assessment in patients with moderate to severe aortic regurgitation (AR). Current clinical guidelines largely rely on uniform thresholds for surgical decision-making, despite growing evidence that cardiac remodeling differs between women and men.
Left ventricular dilatation is a key marker used to guide the timing of aortic valve surgery in AR. Existing recommendations primarily focus on the LV end-systolic diameter index (LVESDi), applying the same cutoff for both sexes. Although LV end-systolic volume index (LVESVi) may offer a more comprehensive assessment of ventricular remodeling, it has only recently been incorporated into guidelines, again using a single threshold regardless of sex. The investigators sought to determine whether sex-specific thresholds for these measures were more closely associated with mortality risk.
The multicenter cohort study included patients with moderate to severe AR and preserved left ventricular ejection fraction (≥50%) treated between December 2003 and December 2022. The analysis drew data from five centers across the Netherlands, Singapore, Hong Kong, Canada, and Romania, with a median follow-up of seven years. Patients with symptoms, acute AR, significant additional valvular disease, or prior valve surgery were excluded to focus on asymptomatic individuals managed medically at baseline.
The researchers reported the following findings:
- The study included 808 patients with a mean age of 56 years; 488 were men and 320 were women.
- During follow-up, 323 patients underwent aortic valve surgery.
- At baseline, left ventricular end-systolic diameter index (LVESDi) was similar in women and men.
- Men had significantly higher left ventricular end-systolic volume index (LVESVi), indicating greater volumetric ventricular remodeling.
- During medical management, 74 deaths were recorded.
- Women showed poorer survival than men, with adjusted six-year survival rates of 80% versus 89%.
- Receiver operating characteristic analyses identified an LVESDi threshold of ≥20 mm/m² for both sexes as being associated with increased mortality.
- LVESVi thresholds linked to higher mortality differed by sex, rising at 40 mL/m² in women and 45 mL/m² in men.
- These associations remained significant after multivariable adjustment and were confirmed with age-adjusted spline analyses.
- Among patients who underwent aortic valve surgery, postoperative survival was similar between women and men.
- Preoperative LVESVi was independently associated with postoperative mortality, with a significant sex-based interaction, underscoring its prognostic importance beyond linear measurements.
The authors concluded that lower LVESDi thresholds than those currently recommended, along with sex-specific LVESVi cutoffs, may improve risk stratification in asymptomatic patients with moderate to severe AR. These findings suggest that incorporating sex-based differences in ventricular remodeling into clinical decision-making could allow for more timely intervention and potentially improved outcomes.
Reference:
Lopez Santi P, Fortuni F, Bernard J, et al. Sex Differences in Left Ventricular Remodeling for Risk Stratification of Patients With Aortic Regurgitation. JAMA Cardiol. Published online January 21, 2026. doi:10.1001/jamacardio.2025.5249
Next Story