Sex-Related Differences in the Pathophysiology, Cardiac Imaging, and Clinical Outcomes of Aortic Stenosis: A Narrative Review

Aortic stenosis (AS) is the most common valvular heart disease in developed countries, and its prevalence is higher in older patients. Clinical studies have shown gender disparity in the pathogenesis and the progression of aortic stenosis. This disparity has led to several overwhelming questions regarding its impact on the clinical outcomes and treatment of the disease and the requirement of personalized sex-specific approaches for its management. Indeed, aortic stenosis differs in the pathophysiological response to pressure overload created by the stenosis in women compared to men, which would translate into differences in cardiac remodeling and clinical outcomes. Several studies have focused on understanding the differences regarding disease progression according to biological gender and have found that sex hormones play a crucial role. Sex hormones affect many metabolic processes, thus activating crucial cell signaling and energy metabolism through mitochondrial activity. Yet, there is still a significant gap in knowledge on how biological sex influences the pathophysiology of AS. In this review, we have discussed studies that point to the role of sex-related physiological differences in the molecular pathways and the clinical presentation of the disease and outcome in women and men. We used the format of narrative review to review and summarize the body of literature without being systematic but with taking great care of considering the most impactful data available to date on the topic, especially randomized trials, metanalyses, and prospective studies and registries when available, as well as experimental studies with rigorous methodological approaches regarding the basic mechanisms and pathophysiology of the disease in women compared to men. The opinion of the authors on a particular issue or finding was expressed when appropriate for clarification.