Afterload-Adjusted Strain Refines Risk Stratification in Aortic Stenosis With Varying Degrees of Aortic Regurgitation

Background and Objectives In aortic stenosis (AS), concomitant aortic regurgitation (AR) may cause heterogeneous left ventricular (LV) remodeling and myocardial responses beyond valve-centric assessment. We evaluated LV geometry and myocardial deformation relative to systolic pressure load in patients with AS across varying AR severity. Methods We analyzed 950 patients with moderate or greater AS categorized as no AR, mild AR, or moderate or greater AR. LV geometry was assessed using LV mass index (LVMI) and relative wall thickness (RWT). Afterload-adjusted strain (AAS) was calculated as absolute LV global longitudinal strain (LVGLS) multiplied by estimated LV systolic pressure. The primary outcome was all-cause death or heart failure hospitalization. Results During a median follow-up of 3.5 years, 122 primary events occurred. Increasing AR severity was associated with LV dilation, increased LVMI, and reduced RWT, whereas AAS remained similar across AR categories. LV geometric measures were not independently associated with the primary outcome. Lower AAS was independently associated with the primary outcome (adjusted HR 1.33 per 500-unit decrease, 95% CI 1.12–1.58; p=0.001; adjusted HR 1.41 per 1-SD decrease, 95% CI 1.14–1.73; p=0.001). AAS provided incremental prognostic value beyond clinical and LV geometric variables, increasing the 1-year AUC from 0.762 to 0.788 (p<0.001). Conclusions Among patients with moderate or greater AS across varying degrees of concomitant AR, increasing AR severity was associated with progressive LV remodeling, whereas lower AAS was independently associated with adverse outcomes. Relating myocardial deformation to systolic pressure load may refine risk stratification beyond clinical and LV geometric measures. Author’s Summary In patients with moderate or greater aortic stenosis and concomitant aortic regurgitation, valve-centric assessment may not fully characterize the heterogeneous ventricular response to combined pressure and volume loading. We assessed left ventricular geometry using LV mass index and relative wall thickness and evaluated afterload-adjusted strain (AAS), which integrates myocardial deformation with the prevailing systolic pressure load. Increasing aortic regurgitation severity was associated with progressive geometric remodeling, whereas lower AAS was independently associated with death or heart failure hospitalization. AAS also improved prognostic discrimination beyond clinical and geometric variables, supporting a more comprehensive, myocardium-centered approach to risk assessment.