Four Key Challenges After a Decade of Consecutive Paradigm Shifts in Wild-Type Transthyretin Amyloid Cardiomyopathy: From Rarely Found to Never Missed.

Wild-type transthyretin amyloid cardiomyopathy has undergone profound transformation over the past decade, evolving from a rarely recognized condition to a disease that should not be missed. This shift has been driven by the use of bone-avid tracer scintigraphy enabling non-biopsy diagnosis, as well as the advent and expansion of disease-modifying therapies. As a result, the number of diagnosed and treated patients has increased substantially. However, important gaps remain in clinical practice, particularly in detection, diagnostic accuracy, and therapeutic decision-making. This review highlights 4 key challenges that will shape the next decade. First, marked geographic disparities in detection suggest underdiagnosis and inequitable access to care. Second, variability in scintigraphic interpretation, particularly due to reliance on planar imaging and modified grading systems, may compromise diagnostic accuracy. Third, the expanding range of therapeutic options, including stabilizers and gene silencers, has increased the complexity of treatment selection and underscores the need for biologically guided strategies. Fourth, patient selection at the extremes of disease severity raises unresolved clinical, ethical, and economic questions regarding when to initiate or withhold therapy. Looking ahead, continued therapeutic innovation and a deeper understanding of disease pathogenesis will be essential. Importantly, characterization of the underlying disease in each patient remains central to advancing clinical care and therapeutic development. If these challenges are addressed, the decade ahead will be even more fruitful.