Proceedings and predictions in cardiac amyloidosis: Unsolved mysteries and challenges for the future

Cardiac amyloidosis (CA) is a progressive and often fatal disorder that may be greatly underdiagnosed and is certainly an underappreciated cause of heart failure. Almost all clinical cases of CA arise from either misfolded monoclonal immunoglobulin light chains (AL) from an abnormal clonal proliferation of plasma cells, or transthyretin amyloidosis (ATTR), a liver-synthesized protein normally involved in the transportation of the hormone thyroxine and retinol-binding protein. Clinical validation of non-invasive criteria for the diagnosis of ATTR-CA and the development of disease-modifying drugs has been shown to improve patients’ survival. Nowadays, the hardest challenge is the recognition of CA at early stages, but clinicians will have to deal with many grey areas and challenges in the future, including mechanisms of amyloid genesis, diagnosis, management, prognostic stratification, therapy and monitoring treatment response.