The calpain/calpastatin system is involved in the development of maladaptive hypertrophy triggered by numerous pathologic stimuli (Wang et al., 2018; Aluja et al., 2019) and as indicated in several studies, leads to platelet aggregation, myocardial ischemia, and ultimately heart failure (Zatz and Starling et al., 2005; Wang et al., 2021). This evidence concerns the gene CAST and heart failure.