Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure.

Pathophysiological roles of cardiac dopamine system remain unknown. Here, we show the role of dopamine D1 receptor (D1R)-expressing cardiomyocytes (CMs) in triggering heart failure-associated ventricular arrhythmia. Comprehensive single-cell resolution analysis identifies the presence of D1R-expressing CMs in both heart failure model mice and in heart failure patients with sustained ventricular tachycardia. Overexpression of D1R in CMs disturbs normal calcium handling while CM-specific deletion of D1R ameliorates heart failure-associated ventricular arrhythmia. Thus, cardiac D1R has the potential to become a therapeutic target for preventing heart failure-associated ventricular arrhythmia. The pathophysiological role of dopamine D1 receptor (D1R) in chronic heart failure remains elusive. Here the authors show that D1R-expressing cardiomyocytes appear in chronic heart failure and play a pivotal role in triggering lethal ventricular arrhythmias.