In summary, the present study demonstrated that ablation of cardiomyocyte-derived BDNF during the developmental stage did not impair embryonic survival, growth or reproduction; however, in young adult hearts, it caused cardiomyocyte death, myocardial degeneration, cardiomyocyte hypertrophy, left atrial appendage thrombosis, decreased cardiac function, increased cardiac inflammation and ROS activity, and metabolic disorders, leading to HF in adult hearts and eventually resulting in a decrease in the one-year survival rate. Here, BDNF is linked to metabolic disease.