Mechanistically, Rac1cKI hearts and cardiomyocytes genetically resistant to Rac1 S-palmitoylation had a profound increase in protein kinase A (PKA) substrate phosphorylation in response to acute β-adrenergic stimulation, as did Rac1cKI hearts subjected to chronic AngII treatment, AT1R overexpression, or pressure overload that correlates with more advanced heart failure phenotypes. Here, AGTR1 is linked to heart failure.