Transcatheter interventions have become a mainstay for the treatment of valvular heart disease [ ]. The success of transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of aortic stenosis [ ]. Mitral transcatheter edge-to-edge repair (TEER) has emerged as a safe and effective treatment for mitral regurgitation (MR) in patients at elevated risk [ , ]. Naturally, given the prevalence of mitral valve disease globally and the limited role of medical therapy, there is great anticipation that transcatheter mitral valve replacement (TMVR) is not far behind [ , ]. Unfortunately, the mitral valve is a dynamic, asymmetrical, and heterogenous structure, with a saddle-shaped annulus and a complex sub-valvular apparatus. As a result, the mitral valve can be afflicted by a large variety of pathologies resulting in either regurgitation and/or stenosis. The wide range of approaches taken in various investigational TMVR system design reflects the many challenges faced when designing a successful device. As a result, development of a safe and effective TMVR has been elusive. A substantial proportion of those with symptomatic mitral valve disease referred for TMVR trials fail stringent screening criteria [ ]. The natural history of these patients is not well-characterized, and details regarding the reasons for screen failure remain limited.