Perspective Chapter: Lipoprotein (a), Cardiac Amyloidosis, and Aortic Stenosis - Underestimated Associations

This chapter aims to address two peculiar aspects of pathophysiology and clinical management of aortic valve stenosis, such as coexistence with cardiac amyloidosis and association with lipoprotein (a). Calcific aortic valve stenosis is the most common heart valve condition requiring surgical or transcatheter aortic valve replacement among adults in Western societies. Lipoprotein (a) has been shown to play an important role in the pathophysiological pathways leading to degenerative aortic stenosis, similar to that in the pathogenesis of atherosclerosis. Studies are needed to verify whether therapies that drastically reduce Lipoprotein (a) serum levels offer the possibility of a first medical treatment to arrest the progression of aortic stenosis. A large percentage of patients with aortic stenosis may have concomitant cardiac amyloidosis, commonly due to wild-type transthyretin. The challenge in this context is to differentiate aortic stenosis alone from aortic stenosis with cardiac amyloidosis, as cardiac amyloidosis shares several clinical, electrocardiographic, and echocardiographic features with the aortic stenosis phenotype. Recognition of transthyretin-related amyloidosis prior to any type of intervention is crucial for adequate risk stratification and to guide downstream management.