Although the characteristics of the 2 arms at the initiation of ATTRibute-CM were well balanced and reflective of a contemporary ATTR-CM population, the imbalance observed in some clinical parameters at the entry to the OLE (eg, New York Heart Association class distribution, National Amyloidosis Centre stage distribution, and NT-proBNP levels) highlights the progression of disease in the ATTRibute-CM placebo arm despite improvements in background clinical management of heart failure in ATTR-CM. This evidence concerns the gene NPPB and heart failure.