Natural history, cardiac remodeling, and prognostic stratification in aortic regurgitation quantified by cardiovascular magnetic resonance

Background Cardiovascular magnetic resonance (CMR) is the reference standard for quantifying aortic regurgitation (AR) and assessing cardiac remodeling. However, the optimal risk stratification of CMR-derived AR severity remains unclear, and the prognostic significance of CMR-defined cardiac remodeling in asymptomatic individuals is not fully understood. Aim To evaluate the prognostic significance of CMR-derived aortic regurgitation fraction (ARF) across the full severity spectrum and to identify structural and functional remodeling markers that predict adverse outcomes in asymptomatic AR patients. Methods We applied deep learning–enabled CMR phenotyping in a large prospective UK cohort to quantify ARF and multidimensional cardiac remodeling. Associations between ARF and a composite primary outcome of heart failure, aortic valve replace-ment, or cardiovascular death were assessed using multivariable Cox regression models. Unsupervised hierarchical clustering and variable importance analysis were used to identify distinct remodeling phenotypes and key sex-specific prognostic markers. Results Among 45,816 participants (mean age 64.1 years; 53% women), 488 experienced the primary outcome over a median follow-up of 4.2 years. A non-linear association between ARF and risk was observed, with a distinct risk inflection point at 11.3%. Beyond this threshold, adjusted hazard ratios increased progressively: 1.78 (95% CI, 1.26–2.53) for ARF 20–29%, 3.17 (95% CI, 1.77–5.67) for ARF 30–39%, and 5.86 (95% CI, 3.34–10.29) for ARF ≥40%. In the asymptomatic AR cohort (n = 11,332), ascending aortic maximum cross-sectional area (>6.0/5.5 cm2/m for men/women), left ventricular (LV) mass (>65/50 g/m2), LV end-systolic volume (>45/35 ml/m2), LV global longitudinal strain (>-15%), and LV ejection fraction (≤55%) emerged as the top predictors of adverse outcomes. Notably, women experienced adverse events at lower thresholds of remodeling than men. Adding these CMR markers to current guideline criteria significantly improved risk discrimination (C-index from 0.76 to 0.81) Conclusion Our study establishes a CMR-derived stratification of AR severity, revealing that clinically meaningful risk begins at a substantially low threshold (ARF >10%). Integrating sex-specific CMR remodeling markers refines risk stratification in asymptomatic individuals, identifying high-risk patients who do not meet current surgical guideline criteria.