Prognostic stratification beyond LV remodeling in aortic regurgitation: a cardiac staging approach

Abstract Background Aortic regurgitation (AR) is associated with heart failure and mortality, yet current surgical criteria focus mainly on LV remodeling. This study aimed to propose a novel staging system that incorporates extra-LV structural changes and assess its prognostic value. Methods A total of 506 patients with at least moderate AR were retrospectively included based on medical records from a single tertiary center between 2006 and 2022. Cardiac damage was categorized into five stages: stage 0 (no structural abnormality), stage 1 (isolated left atrial enlargement), stage 2 (LV remodeling), stage 3 (combined LA and LV involvement), and stage 4 (right-sided involvement). The primary outcome was a composite of all-cause mortality, heart failure hospitalization, and cardiac surgery. Outcomes were compared across stages using Kaplan–Meier analysis and Cox regression, with inverse probability of treatment weighting (IPTW) and doubly robust adjustment to account for confounders. Results Advancing cardiac damage stage was associated with a progressively increased risk of adverse outcomes. In the IPTW-weighted Cox regression model adjusted for age, sex, hypertension, and atrial fibrillation, higher stages were linked to stepwise increases in risk. Adjusted hazard ratios increased across stages, 1.63 (95% CI, 0.69–3.86; p = 0.271) for stage 1, 1.98 (1.35–2.90; p = 0.0005) for stage 2, 4.08 (2.73–6.12; p < 0.001) for stage 3, and 5.24 (2.44–11.26; p < 0.001) for stage 4. Hypertension (HR 1.45; p = 0.017), increased LVEDVi (HR 1.01 per mL/m²; p < 0.001), and impaired global longitudinal strain (GLS ≤ –16.655%; HR 0.51; p < 0.001) were independently associated with the primary outcome. The interaction between stage and GLS was significant (HR 1.53; p = 0.014), indicating that the prognostic utility of GLS decreases as cardiac damage advances. Conclusion This refined cardiac staging system, based on outcome-derived cutoffs for LV and LA volume indices, effectively stratifies risk in patients with significant AR. Higher cardiac damage stages were associated with progressively worse clinical outcomes, suggesting the potential utility of this staging system for clinical risk assessment and decision-making.