Currently in Japan, around 900 patients with advanced heart failure are waiting for heart transplantation under mechanical support or continuous infusion of inotropic agents, and about 70% of them are diagnosed with dilated cardiomyopathy. Although recent advances in high-throughput sequencing technologies have revealed the genetic basis of dilated cardiomyopathy, the molecular basis underlying the rapid progression of advanced heart failure remains to be elucidated. Furthermore, while various pharmacological treatments have been established for most types of heart failure, there are no disease-specific therapy to prevent the juvenile-onset advanced heart failure caused by dilated cardiomyopathy. Our research aim is to elucidate the molecular basis of intractable cardiomyopathies and to develop medical therapy using genetic information, clinical information, human samples and disease-specific iPS cell-derived cardiomyocytes. In this symposium, I would like to present our recent research findings focusing on a female Becker muscular dystrophy carrier and a desmoglein-2-deficient cardiomyopathy patient who developed advanced heart failure and to discuss the possibility of future precision medicine.