CALM1 and heart failure: In conclusion, cardiac hypertrophy/heart failure induced by pressure overload is caused by ROS-mediated destabilization of RyR2 (defective inter-domain interaction→CaM dissociation→Ca2+ leakage), and by increasing the binding affinity of CaM to RyR2 pharmacologically or genetically, the abnormal pathways leading to hypertrophy are inhibited, thereby suppressing the progression to heart failure.