Numerous studies have shown that activating the IGF1/PI3K/AKT signaling pathway has beneficial effects in a wide range of CVD such as myocardial infarction, myocardial I/R injury, diabetic cardiomyopathy, atrial fibrillation, and heart failure.124,195–198 These studies have used global or cardiac-specific genetically modified murine models targeting IGF1R, PI3K, and AKT.107–110,116 However, most of the genetically modified animals have undergone regulated gene expression or activity before the onset of CVD, indicating that the cardiovascular protective effects were predominately preventive. Here, AKT1 is linked to heart failure.