OBJECTIVES/GOALS: Sex differences in aortic stenosis (AS) are vastly underestimated, contribute to disparities in treatment and worse outcomes for women including disproportionately higher mortality rates. This study aims to investigate sex differences in extent of cardiac damage (CD) from pressure overload in AS that may help account for the observed disparities. METHODS/STUDY POPULATION: CD in AS refers to a series of pathologic changes in the myocardium that occur due to chronic pressure overload imposed on the left ventricle by a progressively stenotic aortic valve (AV). These changes are associated with poor outcomes and lower survival in patients with AS. To acquire a deeper understanding of the factors and mechanisms affecting differences in the long-term survival and management of patients with AS, we are proposing to assess baseline stage of CD on echocardiography, and changes in transvalvular hemodynamics and CD stage (Δ CD) over time, in patients with moderate and severe AS at one of 2 large tertiary-care hospitals in MA. We also plan to assess time to and performance of aortic valve replacement (AVR), stratified by hemodynamic severity of stenosis and CD stage, and their interaction with sex. RESULTS/ANTICIPATED RESULTS: We hypothesize that women will have a higher stage of CD on their initial echocardiogram (TTE), demonstrating moderate or greater severity of AS, than men with the same hemodynamic severity of valvular stenosis. We additionally hypothesize that those with more advanced cardiac damage stage will likely have masking of transvalvular progression on echocardiogram. Finally, we anticipate that women will have AVR performed less frequently than men and will have minimal improvement in their Kansas City Cardiomyopathy Questionnaire (KCCQ) scores post-AVR indicative of more heart failure symptoms and a lower quality of life. DISCUSSION/SIGNIFICANCE: This study will seek to better understand sex-based differences in extent of cardiac damage to pressure overload in aortic stenosis (AS) to minimize treatment and outcome disparities for women and allow for more individualized and patient-centered care.